CVS Study pack 2025 6PY updated

6PY011 TBL: Cardiovascular System Cardiovascular system 2025-2026 The diagnosis and clinical management of common/important conditions of the cardiovascular system Facilitators Required References Mohamed Aboudounya Before reading this study-pack re-familiarize yourself with the 5PY022 (M.aboudounya@wlv.ac.uk) Cardiovascular System TBL pack which is available in the CVS folder on Fatima Abbas CANVAS™ (Fatima.abbas4@wlv.ac.uk) o British National Formulary online via Medicines Complete Mumtaz Jivraj o Clinical Pharmacy and Therapeutics, 6th edition, Churchill Livingston 2018, (Mumtaz.jivraj@wlv.ac.uk) Ibrahim AlSabih edited by C. Whittlesea and K. Hodson o (I.alsabih@wlv.ac.uk) Waseem Kaialy the pack o (W.kaialy@wlv.ac.uk) Updated and Adapted from previous material by Alan Hindle, Simren Kachala and Colleagues. Relevant Guidelines (e.g. NICE guidance) and Links referred to throughout Community Pharmacy: Symptoms, Diagnosis and Treatment, 5th Edition, Churchill Livingstone 2020, Edited by P. Rutter o Clinical Medicine, 10th edition, Churchill Livingston 2020, edited by Kumar and Clark o Rang & Dales Pharmacology, 10th edition, Elsevier 2023, edited by Ritter Learning Outcomes discussed within this pack: ✓ Understand the diagnosis, therapeutic and non-drug management (including preventative strategies) of cardiovascular conditions ✓ Identify the key signs, symptoms and investigations (diagnostic and physiological) pertaining to diagnosis including differential diagnosis of CV diseases ✓ Discuss the appropriate clinical management of patients based on patient factors and the application of the evidence base ✓ Discuss the evidence-based treatment selection of CV treatments ✓ Emergency treatments involving the cardiovascular system You should pay particular attention to: • The anatomical recaps • The various definitions that are clarified • The common terminology that is used From that point it will then be useful to cross refer back to disease states covered in year 2 as and when you encounter them in this year 3 pack. A significant emphasis of the year 2 pack was how the pathophysiology of each condition was initially described in order to cement your understanding of how the pharmacological actions correct that adverse pathology. In this pack prior understanding of the pathophysiological processes involved, as well as risk factors and epidemiology, is essential to appreciating how a diagnosis is made. Furthermore, your baseline knowledge of the actions and adverse actions of cardiovascular drugs and the formulations that are commonly encountered are highly significant if you are to make decisions about the most appropriate therapy for a patient. 1 6PY011 TBL: Cardiovascular System Table of Contents HYPERTENSION ................................................................................................................................................................ 4 Drugs that cause hypertension ......................................................................................................................................... 4 Diagnosing hypertension .................................................................................................................................................. 6 Using a Sphygmomanometer............................................................................................................................................ 9 Method for using a Sphygmomanometer......................................................................................................................... 9 Presenting signs/symptoms ............................................................................................................................................ 15 HYPERCHOLESTEROLEMIA .................................................................................................................................. 16 Interpreting blood results ............................................................................................................................................... 16 ISCHAEMIC/CORONARY HEART DISEASE....................................................................................................................... 22 Angina Pectoris ............................................................................................................................................................... 24 Stable angina ................................................................................................................................................................... 24 ACUTE CORONARY SYNDROMES ........................................................................................................................ 28 Clinical Presentation ....................................................................................................................................................... 30 Cardiac enzymes ............................................................................................................................................................. 32 Sub-classifications of ACS................................................................................................................................................ 32 Management of ACS ....................................................................................................................................................... 33 Myocardial Infarction with ST-segment elevation .......................................................................................................... 33 PCI ................................................................................................................................................................................... 33 Thrombolysis (or fibrinolysis).......................................................................................................................................... 34 Unstable Angina and NSTEMI (early management)........................................................................................................ 36 HEART FAILURE ............................................................................................................................................................... 39 Signs, symptoms and classification ................................................................................................................................. 40 Differential diagnoses ..................................................................................................................................................... 41 Management of chronic heart failure ............................................................................................................................. 42 Non-pharmacological management ............................................................................................................................... 42 Pharmacological management ....................................................................................................................................... 42 ARRHYTHMIAS ................................................................................................................................................................ 45 Diagnosis ......................................................................................................................................................................... 45 Non-pharmacological Treatment .................................................................................................................................... 45 Electrical Therapies – Direct Current Cardioversion ....................................................................................................... 45 Pacing Strategies – Pacemakers...................................................................................................................................... 46 Pacing Strategies - ICDs ................................................................................................................................................... 46 Ablation Strategies – Radiofrequency Ablation .............................................................................................................. 46 2 6PY011 TBL: Cardiovascular System Pharmacological Treatment ............................................................................................................................................ 46 Atrial Fibrillation (AF) ...................................................................................................................................................... 47 Rate Control .................................................................................................................................................................... 47 Rhythm Control ............................................................................................................................................................... 48 ‘Pill in the pocket’ Strategy ............................................................................................................................................. 49 Assessment of stroke risk ............................................................................................................................................... 49 Choice of Anticoagulation ............................................................................................................................................... 51 Pharmacists’ Roles in Arrhythmia Management ............................................................................................................ 52 VENOUS THROMBOEMBOLISM (VTE) ................................................................................................................. 52 Prevention of VTE ........................................................................................................................................................... 52 Non-pharmacological VTE prophylaxis ........................................................................................................................... 53 Pharmacological VTE prophylaxis ................................................................................................................................... 54 Diagnosis of VTE .............................................................................................................................................................. 54 Diagnosis of DVT ............................................................................................................................................................. 55 Diagnosis of PE ................................................................................................................................................................ 56 Pharmacological Treatment for DVT and PE ................................................................................................................... 57 Duration of Anticoagulant Treatment ............................................................................................................................ 57 Patient Counselling ......................................................................................................................................................... 58 STROKE.............................................................................................................................................................. 59 Risk Factors and Epidemiology ....................................................................................................................................... 60 Ischaemic Stroke ............................................................................................................................................................. 60 Transient Ischaemic Attack ............................................................................................................................................. 61 Haemorrhagic Stroke ...................................................................................................................................................... 61 Treatment of Stroke ........................................................................................................................................................ 61 TIA Treatment ................................................................................................................................................................. 62 Haemorrhagic Stoke Treatment...................................................................................................................................... 63 Treatment for all Stroke Patients.................................................................................................................................... 63 EMERGENCY RESUSCITATION ............................................................................................................................. 64 3 6PY011 TBL: Cardiovascular System Hypertension Please refer to the NICE guidance available at: https://www.nice.org.uk/guidance/ng136 Presenting signs/symptoms Hypertension is a condition characterized by abnormally high blood pressure which puts extra strain on the blood vessels, heart, brain, kidneys and eyes. Persistent high blood pressure increases the risk of developing coronary artery disease due to the added force against the artery walls. Over time, this extra pressure can damage the arteries, making them more vulnerable to the narrowing and plaque build-up associated with atherosclerosis and increases the risk of a number of serious and potentially life-threatening conditions, such as heart disease, stroke and vascular dementia. Often blood pressure presents with no symptoms and is picked up during a routine check-up. However, at very extremely high blood pressures, symptoms can include: o Fatigue or confusion o Vision problems o Chest pain o Difficulty breathing o Irregular heartbeat o Blood in the urine o Pounding in the chest, neck or ears It is important to be able to differentiate hypertension from other conditions which may be causing blood pressure to increase up such as anxiety, white coat syndrome, sleep apnoea, thyroid issues etc. This is done by carrying out relevant investigations to exclude other pathologies such as ambulatory blood pressure monitoring (ABPM), thyroid function tests etc. and if found to be positive treated appropriately. Drugs that cause hypertension It can become easy to think of hypertension as a disease that can be treated by drugs, but what about when drugs cause blood pressure to become raised? As pharmacists you will see prescriptions every day and need to make clinical decisions on the suitability of the prescribed medicines taking into consideration patient factors such as whether the patient is elderly, pregnant, of child bearing age, etc. When a particular medicine is not suitable or there is a clinical interaction, you will need to prioritise the patient’s treatment and advise on suitable alternatives. Activity On the page below is a table with a list of drug classes which may cause high blood pressure, some of which are available to buy OTC. Add drug names that fit into the class and explain how each drug/class of drug can cause blood pressure to become raised and whether it is available to purchase OTC. What could you do if one of your patients who was hypertensive was about to start taking any of the following drugs? 4 6PY011 TBL: Cardiovascular System HINT: Use a combination of the BNF sections covering the relevant drug classes and a pharmacology textbook such as Rang and Dale’s ‘Pharmacology’ to identify drug examples and summarise their mechanisms of action in raising BP; and clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ and Rutter’s ‘Community Pharmacy: Symptoms, Diagnosis and Treatment’ to check for alternative treatment options. Drug groups and example(s) NSAIDs: Ibuprofen… Recreational drugs: Amphetamine, ecstasy, cocaine… Mechanism of raising BP Classification NSAIDs cause fluid retention and decrease renal OTC function causing BP to become raised and putting greater stress on the heart and kidneys. NSAIDs can also increase the risks of heart attack or stroke, especially in higher doses. Alternative options/plan Recommend alternative analgesia such as paracetamol or recommend the lowest dose possible of NSAID N/A Nasal decongestants: Pseudoephedrine… Migraine medication: … Oestrogen containing preparations: Oral contraceptive pills… Antidepressants… Corticosteroids… Cyclosporin 5 6PY011 TBL: Cardiovascular System Diagnosing hypertension Diastolic blood pressure and systolic blood pressure are both measured in millimetres of mercury (mmHg). The ideal blood pressure is considered to be between 90/60mmHg and 120/80mmHg. Targets vary but high blood pressure is considered to be 140/90mmHg or higher. Low blood pressure is considered to be 90/60mmHg or lower. A blood pressure reading between 120/80mmHg and 140/90mmHg could mean the patient is at risk of developing high blood pressure if they don't take steps to keep their blood pressure under control. If a patient presents with a blood pressure reading of greater than 140/90mmHg they should be recommended for ambulatory blood pressure monitoring (ABPM). ABPM is when your blood pressure is measured as you move around, living your normal daily life. It is measured for up to 24 hours. A small digital blood pressure monitor is attached to a belt around your waist and connected to a cuff around your upper arm. This gives a more accurate picture of how your blood pressure changes throughout the day. It avoids the problems of ‘white coat’ syndrome (where your blood pressure rises because you are feeling anxious about being tested by a healthcare professional). All adults over 40 are advised to have their blood pressure checked at least every five years and more often if their blood pressure is close to 140/90mmHg. Please click on the below hyperlink to see a short video on how a ABPM works and installed. Please note: Frequency in which the readings are taken can vary based on the brand of device used. https://www.youtube.com/watch?v=waOXya_Tr98 Investigations to complete for people with hypertension: o Test for the presence of proteinuria by sending a urine sample for estimation of the albumin: creatinine ratio and test for haematuria using a reagent strip. (These tests are important in detecting renal disease). o Take a blood sample to measure glycated haemoglobin (HbA1C), electrolytes, creatinine, eGFR, serum total cholesterol and HDL cholesterol o Examine the fundi (interior lining of eyeball) for the presence of hypertensive retinopathy o Arrange for a 12-lead electrocardiograph (ECG) to be performed. 6 6PY011 TBL: Cardiovascular System 7 6PY011 TBL: Cardiovascular System Activity There are different types of blood pressure. Research each one and makes notes on how they are different to each other in both their presentation and their treatments. • Essential/primary hypertension • Secondary hypertension • Resistant hypertension 8 6PY011 TBL: Cardiovascular System Using a Sphygmomanometer Automated blood pressure machines are in wide-spread use however they may not be suitable for all patients, particularly those with arrhythmias, pre-eclampsia, atrial fibrillation, and certain vascular diseases. If the pulse is irregular, an automated blood pressure device can give inaccurate readings due to beat-to-beat variation, A healthcare professional can check for this by palpating the radial or brachial pulse before checking the blood pressure. If the pulse is irregular blood pressure should be measured manually with auscultation over the brachial artery. Patients with an irregular or rapid pulse should be referred to their doctor. Method for using a Sphygmomanometer https://www.youtube.com/watch?v=f6HtqolhKqo 1. To begin blood pressure measurement, use a properly sized blood pressure cuff, ensure patient is relaxed and both feet are fixed to the ground (not crossed). 2. Wrap the cuff around the upper arm with the cuff's lower edge one inch above the elbow pit. Place forearm in 90 degree angle ideally resting on the table. 3. Find the pulse, place your two fingers over the radial artery, rapidly inflate the cuff until you no longer feel the radial pulse (where the cuff occludes the artery). This will give you a rough indication of the systolic BP. 4. Release air from the cuff at a moderate rate (3mm/sec). Ensure all air is released from the cuff. 5. Lightly press the stethoscope diaphragm over the brachial artery just below the cuff's edge 6. Reinflate the cuff 20-30mm above estimated systolic BP and listen with the stethoscope 7. Release air from the cuff at a moderate rate (3mm/sec) and simultaneously observe the dial or mercury gauge. 8. The first knocking sound (Korotkoff) is the patient’s systolic pressure (As cuff pressure is lowered the blood will flow only when systolic pressure is above cuff pressure producing sounds of Korotkoff.) 9. These sounds will be heard until the cuff pressure is equal to the diastolic pressure causing the sounds to disappear. When the knocking sound disappears, that is the diastolic pressure 10. Record the pressure in both arms and note the difference; also record the subject's position (supine), which arm was used, and the cuff size (small, standard or large) 11. If the subject's blood pressure is elevated, measure two additional times, waiting a few minutes between measurements. Activity Using your BNF, read the chapter on cardiovascular, particularly the drug class sections, and use the information to fill in the following table on drugs used to treat hypertension. You can also use a pharmacology textbook such as Rang and Dale’s ‘Pharmacology’ to help you if you need to find more detail on the mechanism of action. Clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ and Rutter’s ‘Community Pharmacy: Symptoms, Diagnosis and Treatment’ often provide information on the MOST IMPORTANT side-effects, counselling and monitoring points that you need to know. 9 6PY011 Group ACE inhibitors (ACEi) Examples Enalapril Lisinopril Perindopril Ramipril TBL: Cardiovascular System Mechanism of action ACEi produce vasodilation by inhibiting the formation of angiotensin II. Reduced angiotensin II formation and inhibition of bradykinin breakdown lead to vasodilatation. Reduced aldosterone production reduced sodium and water retention Side effects Dry cough, hyperkalaemia, angiodema, dizziness, GI disturbance, skin reactions Counselling points Monitoring points • • • Ramipril can cause dry cough, if affected can change to ARB. • Take first few doses at nighttime due to first dose hypotension. • Specialist supervision required when initiating with diuretics and/or in heart failure. • Be mindful that it can cause dizziness/light headedness when newly started/at dose titration. • Blood pressure Renal function (patients may have renal artery stenosis) Potassium levels Angiotensin-2 Receptor Blockers (ARB/AII antagonist) Calcium Channel Blockers (CCB) Diuretics Furosemide… Amiloride and spironolactone Renin inhibitors Beta-blockers Alpha-blockers 10 6PY011 TBL: Cardiovascular System Activity: NICE guidance states that hypertension should be treated in a step-by-step approach. It also emphasises the importance of patient education. Read through the guidance using the link below and make notes on each step: https://www.nice.org.uk/guidance/ng136 Step 1 Step 2 Step 3 Step 4 11 6PY011 TBL: Cardiovascular System 12 6PY011 TBL: Cardiovascular System Hypertensive Emergency A hypertensive emergency (also known as hypertensive crisis) is considered if a patient presents with BP with a reading of 180/120mmHg or over. Symptoms that may also present with severely raised BP are: o Severe headaches/vomiting o Severe anxiety o Shortness of breath o Nosebleeds o Retinal haemorrhage In any of the above situations urgent medical assistance should be sought i.e. A+E referral. According to NICE/BNF, anything above 180/110mmHg is ‘severe hypertension’. However, if the BP is above 180/110mmHg and there is no acute target-organ damage (damage of target organs, such as heart, kidney, and brain) then this is considered a ‘hypertensive urgency’ case, not a hypertensive emergency. For it be considered a hypertensive emergency, the key difference is that there must be acute target organ damage, and this usually occurs when the diastolic BP is greater than 120, hence why a hypertensive emergency is often referred to as a BP reading above 180/120mmHg. The important thing to remember is that there is no absolute value of BP that separates the two syndromes (urgency and emergency). Instead, the most important distinction is whether there is evidence of impending or progressive targetorgan damage. Pre-eclampsia https://www.nice.org.uk/guidance/ng133 Pre-eclampsia is a condition that can occur in pregnant women and is characterised by high blood pressure (greater than 140/90mmHg) and a large amount of protein in the urine. It usually occurs in the third trimester and is a medical emergency. Signs and symptoms that may present in the pharmacy by a pregnant woman that would warrant an urgent referral include: • Severe headache • Problems with vision, such as blurring or flashing before the eyes. • Severe pain just below the ribs • Vomiting • Sudden swelling of the face, hands, or feet. Activity See the table on the next page. There are many causes of high blood pressure such as taking oral contraceptive pills, having a thyroid disease, having arterial disease, etc. The following table lists a few but can you think of any more? Discuss why each is a risk factor. List the non-pharmacological interventions that you can use to counsel patients with hypertension. 13 6PY011 TBL: Cardiovascular System HINT: Use a clinical pharmacy textbook such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ or relevant NICE Clinical Knowledge Summaries to help you find information on management options and addressing risk factors. Hypertension risk factor Salt excess Explain High salt intake means there is more sodium in the blood stream therefore less water is removed from the kidneys. Non-pharmacological interventions Advise patient to reduce salt intake Weight Family history Lack of exercise African/Caribbean descent Smoking Coffee/alcohol Lack of exercise Disturbed sleep or not getting enough sleep. 14 6PY011 TBL: Cardiovascular System Hypercholesterolemia Please refer to the guidance available at: https://www.nice.org.uk/guidance/ng238 Presenting signs/symptoms Cholesterol is a waxy substance that may deposit as plaques on artery walls causing narrowing of arteries therefore restricting blood flow to organs such as the heart and brain. Additionally, these plaques may rupture and cause dangerous blood clots. High cholesterol can cause atherosclerosis and increase the risk of complications such as myocardial infarction, coronary artery disease and stroke. Cholesterol plays a pivotal role in synthesising bile acids, steroid hormones, and fat-soluble vitamins (Vitamin A, D, E, and K). Although cholesterol is essential for the body functioning, a high cholesterol level indicates the impending risk of heart disease. On average, the UK has one of the highest cholesterol levels in the world. Despite this, high cholesterol doesn't usually produce any obvious symptoms. Here are some signs and manifestations that you may come across in the pharmacy: • Angina • Xanthomas, which are fatty skin deposits on the elbows, buttocks, knees and tendons. • Xanthelasmas, which are cholesterol deposits around the eyelids • Corneal arcus, which are cholesterol deposits around the corneas 15 6PY011 TBL: Cardiovascular System Familial hypercholesterolaemia (FH) FH is an inherited condition that results in high levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. FH is a genetic disorder, a result of a mutated gene on chromosome 19. Unlike recessive genetic disorders that require both sides of the family to have the condition, FH is autosomal dominant, meaning that a child may have the condition even if only one parent has the mutated gene. Children who inherit the mutated gene from both parents are at greater risk for heart attack and death before age 30. Men with FH tend to have heart attacks when they’re in their 40s or 50s. Eighty-five percent of men with this condition have a heart attack by the time they reach 60. Women with this condition tend to have heart attacks in their 50s or 60s. More on the identification and management of this rare but serious condition can be found on the following link: https://www.nice.org.uk/guidance/cg71 Diagnosing hypercholesterolemia Usually, high cholesterol level is diagnosed with a simple blood test. To prepare for the test, the patient should have fasted (no food or drink except water) for 10-12 hours beforehand. This is called a fasting blood test and is usually done first thing in the morning between dinner the night before and a late breakfast. A syringe of blood may be taken or a finger prick test can be carried out. GPs will usually arrange cholesterol blood tests for people who are over 40 and those with other risk factors for high cholesterol such as: o o o o o o Being overweight or obese Having high blood pressure Having diabetes Having a family history of heart or cardiovascular problems Having a family history of hypercholesterolaemia or inherited high cholesterol Other medical conditions, age, sex and ethnic background can also make a difference. Hypercholesterolemia is diagnosed by taking a sample of a patient’s blood and sending it to a laboratory for analysis. Results are returned as lipids and liver function tests. There are two types of lipid HDL and LDL and the blood results will give you a total cholesterol too. Often clinicians will also check a patient’s thyroid function, to ensure it isn't contributing towards the raised cholesterol. Interpreting blood results Cholesterol tests Additional information TC (Total cholesterol) LDL cholesterol, HDL cholesterol and other lipid components N.B. Average in the UK is around 5.5 mmol/l for men and 5.6 mmol/l for women. LDL cholesterol can build up on the walls of your arteries and increase the chances of getting heart disease. The lower the LDL cholesterol number, the better it is for the patient’s health. HDL cholesterol protects against heart disease by taking the "bad" cholesterol out of the blood and keeping it from building up in your arteries. Higher number for this cholesterol is a good sign. Fats carried in the blood from the food we eat: Excess calories, alcohol or sugar in the body are converted into triglycerides and stored in fat cells throughout the body LDL (Low density lipoprotein cholesterol) Also referred to as: Bad cholesterol HDL (High density lipoprotein cholesterol) Also referred to as: Good cholesterol TG (Triglycerides) Recommended parameters 5.0 millimoles per litre (mmol/L) or lower 3mmol/L or lower. 1 mmol/L or higher 1.7 mmol/L or lower 16 6PY011 TBL: Cardiovascular System People with higher risks, such as heart disease or high blood pressure will be set lower targets: o o o Total cholesterol of 4mmol/L or lower LDL of 2mmol/L or lower The ratio of total cholesterol to HDL - total cholesterol divided by HDL - should be below 4. Clinicians will set individual cholesterol targets for patients based on their overall risk factors. Treatment may involve dietary changes to cut down on saturated fats, increasing exercise, or taking cholesterol lowering medication. Even if cholesterol is not high there may be occasions when lipid lowering therapy is still recommended, for example in patients at high risk of developing cardiovascular disease. NICE recommends offering atorvastatin 20 mg daily for primary prevention to people who have a 10% or greater 10-year risk of developing CVD (estimated using the QRISK3 assessment tool, please visit the website), including those with type 2 diabetes and CKD. QRISK3 is an algorithm for predicting cardiovascular risk. It estimates the risk of a person developing cardiovascular disease (CVD) over the next 10 years and can be applied to those aged between 35 and 74 years. Activity: There are many causes of high cholesterol levels, below is a list of some of them, can you think of any more? Discuss why each is a risk factor HINT: Use a clinical pharmacy textbook such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ or relevant NICE Clinical Knowledge Summaries to help you find information on management options and addressing risk factors. • Gender- women tend to have higher cholesterol than men • Pregnancy • Diabetes • Kidney disease • Polycystic ovary syndrome 17 6PY011 TBL: Cardiovascular System • Underactive thyroid gland • Certain drugs, e.g. contraceptives, diuretics, beta-blockers, anti-depressants • Any other risk factors: Drug choice The main choice of drug for treatment of hypercholesterolemia is a statin, however, sometimes, a non-statin lipid lowering drug can be offered such as ezetimibe or cholestyramine. The decision whether to start statin therapy should be made after an informed discussion between the clinician and the person about the risks and benefits of statin treatment, considering additional factors such as potential benefits from lifestyle modifications, informed patient preference, comorbidities, polypharmacy, general frailty and life expectancy. Before starting statin treatment, baseline blood tests should be conducted and the person should be clinically assessed; comorbidities and secondary causes of dyslipidaemia should be treated. When a decision is made to prescribe a statin, the NICE guideline on lipid modification (https://www.nice.org.uk/guidance/ng238) recommends using a statin of high intensity and low acquisition cost. Statins are grouped into 3 different intensity categories according to the percentage reduction in low-density lipoprotein cholesterol (LDL-C): The choice of treatment and dose will depend on the % reduction of LDL that is being aimed for. Fluvastatin Low intensity (20–30% LDL-C reduction) 20–40 mg daily Medium intensity (31–40% LDL-C reduction) 80 mg daily High intensity (more than 40% LDL-C reduction) - Pravastatin 10–40 mg daily - - Simvastatin 10 mg daily 20–40 mg daily 80 mg daily. Atorvastatin - 10 mg daily 20–80 mg daily Rosuvastatin - 5 mg daily 10–40 mg daily 18 6PY011 TBL: Cardiovascular System The only high-intensity statin specifically named in the NICE guidelines is atorvastatin 20–80 mg daily. Other possible high-intensity statins are rosuvastatin 10–40 mg daily and simvastatin 80 mg daily. The MHRA has advised that there is an increased risk of myopathy associated with simvastatin 80 mg daily, and that this dose should be considered only in people with severe hypercholesterolaemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risk. Statins used in Primary Prevention Atorvastatin 20 mg daily should be offered for primary prevention to people who have a 10% or greater 10-year risk of developing CVD (estimated using the QRISK®3 assessment tool ( https://qrisk.org ) including those with type 2 diabetes and CKD. In people with type 1 diabetes treatment should be started with atorvastatin 20 mg daily. Primary prevention may be considered in type 1 diabetic patients with any of the following risk factors: • • • adults who are older than 40 years those who have had diabetes for more than 10 years who have established nephropathy, or who have other CVD risk factors Statins used in Secondary Prevention Statin treatment for people with CVD (secondary prevention) should usually start with atorvastatin 80 mg daily. However, in people with CKD the initial dose should be 20 mg daily, and in other people a dose lower than 80 mg daily should be used if there are potential drug interactions with existing therapy, a high risk of adverse effects or the person prefers a lower dose. Monitoring with statins Total cholesterol, HDL cholesterol and non-HDL cholesterol should be measured in all patients who have been started on high-intensity statin treatment as above after 3 months of treatment, aiming for a greater than 40% reduction in non-HDL cholesterol. If this reduction in non-HDL cholesterol is not achieved; • discuss adherence and the timing of the dose • optimise adherence to diet and lifestyle measures • consider increasing the dose if the person started on less than atorvastatin 80 mg daily and if they are judged to be at higher risk because of comorbidities, risk score or using clinical judgement. The dose of atorvastatin should be increased from 20 mg in people with CKD receiving it for primary or secondary prevention of CVD if a greater than 40% reduction in non-HDL cholesterol is not achieved and the person's eGFR is 30 ml/min/1.73 m2 or more. If their eGFR is less than this, any increase in dose should be discussed with a renal specialist. It is also advisable that healthcare professionals provide annual medication reviews for people taking statins; using these reviews to discuss medication adherence and lifestyle modification, address CVD risk factors and monitoring for adverse effects/intolerance of statins. If a person is not able to tolerate a high-intensity statin, the aim should be to treat with the maximum tolerated dose. Many people who stop treatment due to side effects or adverse effects, especially muscle pains, may be able to restart treatment on the same or a different statin. The patient should be advised that any statin at any dose reduces CVD risk. If someone reports adverse effects when taking high-intensity statins, the following strategies should be discussed with them; • • • stopping the statin and trying again when the symptoms have resolved to check if the symptoms are related to the statin reducing the dose within the same intensity group changing the statin to a lower intensity group 19 6PY011 TBL: Cardiovascular System Ezetimibe People with primary hypercholesterolaemia should be considered for ezetimibe treatment in line with the licencing indication. Ezetimibe monotherapy is as an option for treating primary (heterozygous-familial or non-familial) hypercholesterolaemia in adults in 2 broad situations: • • As an alternative to a statin in people in whom statins are contraindicated or not tolerated; intolerance is defined as the presence of clinically significant adverse effects that represent an unacceptable risk to the patient or that may reduce compliance with therapy. In addition to initial statin therapy in people who have started statin treatment but whose serum total or LDL cholesterol concentration is not appropriately controlled either after appropriate dose titration or because dose titration is limited by intolerance to the initial statin therapy (defined as above) and consideration is being given to changing from initial statin therapy to an alternative statin. In the second of the situations above, in people with non-familial hypercholesterolaemia, adding ezetimibe to atorvastatin (the initial statin therapy recommended in the guideline) is an option if (and only if) a greater than 40% reduction in non-HDL cholesterol is not achieved: • • • despite optimising adherence and timing of the dose of atorvastatin and optimising adherence to diet and lifestyle measures, and increasing the dose of atorvastatin (if started at less than 80 mg daily) is not effective or not tolerated or the person has to decrease the dose because of tolerability problems, and changing to a different statin is being considered. Bile acid sequestrants, fibrates and nicotinic acid See the NICE guideline on familial hypercholesterolaemia ( https://www.nice.org.uk/guidance/cg71 ) on the possible use of bile acid sequestrants, fibrates and nicotinic acid in people with this condition. Bile acid sequestrants and nicotinic acid should not be offered for primary or secondary prevention of CVD including in people with CKD or type 1 or type 2 diabetes. Omega-3 fatty acid compounds People with or at high risk of CVD should be advised to consume at least 2 portions of fish per week, including a portion of oily fish. However, it is advised that omega-3 fatty acid compounds should not be offered for primary or secondary prevention of CVD, alone or in combination with a statin, including in people with CKD or type 1 or type 2 diabetes. Moreover, healthcare professionals should tell people that there is no evidence that omega‑3 fatty acid compounds help to prevent CVD. In addition, healthcare professionals should not offer or advise people who have had an MI to use omega‑3 fatty acid capsules or omega‑3 fatty acid supplemented foods to prevent another MI. Icosapent ethyl is the only drug available in restricted circumstances however it comes with a significantly long inclusion criteria (see NICE TA805 for further information). Monoclonal antibodies For recommendations on managing primary heterozygous familial hypercholesterolaemia in people whose LDL C levels are not adequately controlled despite maximal tolerated lipid-lowering therapy, see the NICE technology appraisal guidance on alirocumab and evolocumab. Activity Using your BNF, read the chapter on lipid lowering therapy and use the information to fill in the following table on drugs used to treat hypercholesterolaemia: HINT: Use a combination of the BNF sections covering the relevant drug classes and a pharmacology textbook such as Rang and Dale’s ‘Pharmacology’ to identify drug examples and summarise their mechanisms of action; and clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ and 20 6PY011 TBL: Cardiovascular System Rutter’s ‘Community Pharmacy: Symptoms, Diagnosis and Treatment’ to help you find the MOST IMPORTANT cautions, contraindications, side effects, monitoring, interactions and counselling. Group Statin Mechanism of action Simvastatin Rosuvastatin Atorvastatin Examples Side effects Competitively inhibit HMG CoA reductase, an enzyme involved I cholesterol synthesis, especially in the liver Rhabdomylosis Counselling points/interactions Report any muscle aches/cramps, do not take with macrolides Monitoring Lipid profile; LFTs (transaminases – upper limits of normal); Creatine kinase; fasting blood glucose or HbA1c in patients at risk of DM Cholesterol absorption inhibitor Bile acid sequestrants Nicotinic acid Fibrates Gemfibrozil Monoclonal antibodies 21 6PY011 TBL: Cardiovascular System Non-pharmacological interventions Over half of the adults in the UK have high cholesterol (>5mmol/L); as pharmacists it is important that you offer patients education on ways in which they can help to prevent and reduce raised cholesterol levels. Furthermore, many people cannot tolerate the side effects associated with many lipid lowering therapies and or may want to reduce their dependence on multiple medications; as a healthcare professional you need to tailor advice on how this can be implemented: • • • • • • • • • Have cholesterol levels checked regularly and take medications if prescribed. Start and continue an exercise program with 30-60 minutes of vigorous activity at least 3 or 4 days a week. Maintain a healthy weight; lose weight if needed. Choose a wide variety of foods that are low in saturated fat, cholesterol and sodium and more unsaturated fats - Read food labels. Limit alcohol intake. Don't smoke and avoid "second hand" smoke. Have blood pressure checked regularly and take steps to lower it if it's high. If patient has diabetes, follow doctor's recommendations for treatment. Advice patient to become an active participant in making treatment decisions and in solving problems relating to their health. Ischaemic/Coronary Heart Disease TAKE TIME TO UNDERSTAND THE BELOW DIAGRAM!! THIS WILL ALLOW YOU TO BETTER UNDERSTAND THE SIMILARITIES AND DIFFERENCES BETWEEN THE UPCOMING DISEASE STATES. 22 6PY011 TBL: Cardiovascular System You should re-read the 5PY022 CVS pack sections on cardiovascular (CV) disease risk factors and the process of atherosclerosis, together with details of the epidemiology and impact of cardiovascular disease at the national level. Make notes below on the types of conditions that come under the umbrella term of cardiovascular disease (as opposed to heart disease). Hint: Not all cardiovascular diseases involve coronary arteries (arteries which supply the heart muscle tissue with oxygenated blood) but we are generally talking about atherosclerotic arterial disease when considering these conditions. Categorise the following risk factors for CV disease in to modifiable and non-modifiable: Increasing age; abdominal obesity; sex; hypertension; pre-existing CV disease; smoking; hyperlipidaemia; family history of CV disease; diabetes mellitus; South Asian descent; alcohol intake; diet; physical exercise Modifiable Non-modifiable Which of the above two categories is the most important and why? 23 6PY011 TBL: Cardiovascular System Angina Pectoris Using the year 2 CVS pack, re-familiarise yourself with the definitions and descriptions of stable angina, unstable angina, Prinzmetal’s variant angina, decubitus angina and nocturnal angina. For the purposes of this pack, you will look specifically at stable angina and unstable angina, the latter being covered under Acute Coronary Syndromes. Stable angina https://www.nice.org.uk/guidance/cg126 This type of angina occurs in stable coronary artery disease where stable atheromatous plaques form in one or more major coronary arteries. Symptoms only tend to occur in patients that have significant stenosis (narrowing) of a coronary artery (>~70%). This permanent restriction of blood flow causes a mismatch between the supply and the demand of oxygenated blood to the myocardium at times of stress or activity when cardiac output (CO) increases (remember CO is a function of heart rate and stroke volume; CO = HR x SV). Hence, patients are more likely to experience ischaemic pain when precipitated by exercise, stress, or temperature change. For this reason, symptoms in stable angina are very predictable and occur in a reproducible manner, hence pain can be relieved by either stopping the trigger e.g. by ceasing the activity or by using GTN (which dilates coronary arteries) prior to undertaking the causative activity. The symptoms of stable angina include: • Retrosternal chest heaviness (constricting/gripping/tight/diffuse [not sharp]) • Additional features: o Radiation to back/arms/neck/jaw o Associated breathlessness o Autonomic symptoms (such as tachycardia/sweating/pallor/clamminess) They are similar to those which can be experienced during a heart attack or in unstable angina and, while generally symptoms are less severe, the fundamental difference compared to acute coronary syndromes lies in the pattern of pain and in the response to glyceryl trinitrate. In other words, in stable angina, the symptoms are entirely predictable and stable. When making a diagnosis it is important to note that the fundamental features of stable angina include both the reversibility of the symptoms and the repetitiveness of the attacks over time (months to years). The pathophysiological mechanisms by which stable angina develops are eloquently described on the following video: https://www.youtube.com/watch?v=7PsDK2R95Sg (Note: that the UK pronunciation of angina, emphasises the ‘I’) A diagnosis of stable angina can be made clinically i.e. based upon physical examination, symptoms, history and risk factors but there are various investigations which may need to be performed when the diagnosis is uncertain. The outline of diagnosis can be seen in the following links: 24 6PY011 TBL: Cardiovascular System Activity Refer to the below links and make notes on the diagnosis of stable angina including categorisation between typical angina, atypical angina and non-anginal chest pain; and tests such as ECG, exercise ECG, CT Calcium scoring, noninvasive functional testing, invasive angiography and non-invasive CT angiography. NICE guideline CG95 Recent-onset chest pain of suspected cardiac origin found at https://www.nice.org.uk/guidance/cg95 NICE CKS https://cks.nice.org.uk/angina https://cks.nice.org.uk/topics/angina/diagnosis/assessment-of-stable-chest-pain/ Stable Angina Non-stable Angina Non-anginal Chest Pain Diagnosis Tests Other Information 25 6PY011 TBL: Cardiovascular System Treatment of stable angina The pharmacological treatment of patients with stable angina should be considered with reference to three overarching aims: 1. Immediate resolution of angina attacks (or prevention of predictable attacks using sublingual GTN). 2. Decreasing the severity and/or frequency of angina attacks using anti-anginal drugs such as beta-blockers, calcium channel blockers, long-acting nitrates or potassium channel activators. 3. Providing secondary prevention treatment as the patient by definition has existing cardiovascular disease in the form of antiplatelet therapy, high intensity statins and ACE inhibitors (for patients with diabetes mellitus or another suitable indication for an ACE inhibitor) in accordance with other guidelines. Complete the following drugs table using the angina section and relevant sections in the BNF: HINT: Use a combination of the BNF sections covering the relevant drug classes to identify drug names and formulations; and clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ to help you find the MOST IMPORTANT cautions, contraindications, side effects, monitoring, interactions and counselling. Drug names and formulations Key cautions* and contraindications** Key adverse effects AND monitoring Important interactions Other notes and counselling Glyceryl trinitrate Calcium channel blockers (dihydropyridine types and diltiazem) Beta-blockers Long-acting nitrates Potassium channel activators Ivabradine Ranolazine 26 6PY011 TBL: Cardiovascular System Using BNF chapter 2.7 and the 2018 NICE Clinical Knowledge Summary (CKS) for Angina (new diagnosis) [http://cks.nice.org.uk/angina] complete the table below to summarise the first, second and third line strategies for reducing the severity and/or frequency of stable angina attacks. Consider the following anti-anginal drugs: calcium channel blockers, beta-blockers, long acting nitrates (e.g. isosorbide mononitrate), nicorandil, ivabradine and ranolazine; as well as revascularisation therapies in your summary. Strategies for reducing the severity and/or frequency of angina attacks for patients suffering attacks more than twice a week First line strategy Second line strategy Third line strategy Co-morbid conditions such as atrial fibrillation, chronic kidney disease, diabetes, chronic heart failure, hypertension, obesity, rheumatoid arthritis, and stroke and TIA should be optimally managed. Patients with any form of angina will also require advice on maintaining a healthy diet and lifestyle, smoking cessation (if applicable); and on implications for manual work, driving, flying and sexual activity. Using the NICE CKS make additional notes on the advice which should be given to newly diagnosed stable angina patients including those listed above. 27 6PY011 TBL: Cardiovascular System Acute coronary syndromes Please see the NICE guidance available at: https://www.nice.org.uk/guidance/ng185 The 5PY022 CVS pack briefly mentions unstable angina and myocardial infarction (MI) and covers the pharmacology of the drugs used to treat them. Both of these conditions are, in fact, part of a spectrum of coronary events known as Acute Coronary Syndromes (ACS) [Grab your reader’s attention with a great quote from the document or use this space to emphasize a key point. To place this text box anywhere on the page, just drag it.] AKA Coronary Heart Disease (CHD)/Ischaemic Heart Disease (IHD) Patients who have stable angina have atheromatous plaques in their coronary arteries which, while extending slowly, are stable in nature. As described above the extent of stenosis determines whether or not angina pain occurs (due to demand for oxygenated blood outstripping supply that is able to reach the myocardium). The following video provides an animated representation of how atheromatous plaques form in coronary arteries. It also shows what happens when plaques rupture and a resulting thrombus completely occludes a coronary artery causing a heart attack (myocardial infarction): https://www.youtube.com/watch?v=T_b9U5gn_Zk In ACS a plaque becomes unstable and ruptures exposing its lipid rich core. In itself this does not cause a problem except that circulating platelets become attracted to the exposed core and begin to aggregate which subsequently triggers thrombosis (clot formation). A thrombus can then either intermittently or partially occlude a coronary artery or it can completely block it. Thus, in ACS, three eventualities are possible: 1. Where total occlusion of a major coronary artery occurs no oxygenated blood can reach the part of the myocardium supplied by that artery and so death of heart muscle tissue will occur relatively quickly (over minutes or tens of minutes). Death (irreversible necrosis) occurs through the full thickness of the myocardium in the area of the myocardium perfused by that coronary artery. This is known as a full-blown MI (heart attack); ST elevation MI (STEMI or STE-ACS); or, sometimes, Q wave MI. 28 6PY011 TBL: Cardiovascular System 2. So-called intermittent occlusion occurs when a thrombus may break up or dislodge and move downstream to a smaller branch of a coronary artery which can become occluded. This will cause myocardial damage to a lesser extent which is still an MI and is referred to as a non-ST elevation MI (NSTEMI). There is a nevertheless danger that thrombosis will extend further and cause full blown STEMIs. 3. So-called partial occlusion occurs where a thrombus partially (but not completely) occludes a coronary artery. The plaque rupture and subsequent thrombus formation has made the situation unpredictable but no death of myocardial tissue occurs. These unpredictable angina symptoms are known as unstable angina (UA). Like 2 above there is a danger that thrombi will extend, break up or dislodge and cause full blown STEMIs. Both 2 and 3 above are grouped together as Non-ST Elevation Acute Coronary Syndromes (NSTEACS/NSTEMI) since the treatment pathway for these is different to that taken in the very urgent full blown STEMI situation. Because of the unstable nature of the events which cause ACS all of these situations can occur in patients who have no previous awareness that they have any atherosclerotic damage in their coronary arteries. In other words a patient with less than 60 or 70% stenosis who has never suffered an angina attack can still have a plaque which ruptures and causes ACS. This is why patients can suffer heart attacks without any knowledge that there was previously anything wrong. 29 6PY011 TBL: Cardiovascular System The following video provides a more detailed description of the pathophysiology of coronary artery disease including stable angina and ACS. https://www.youtube.com/watch?v=EATkbpqlxvc Diagnosing ACS Acute coronary syndromes are differentially diagnosed (and from stable angina) on the basis of: • • • Presentation: symptoms, examination and risk factors Electrocardiography (ECG) changes Cardiac markers Clinical Presentation Non-ST elevation MI (NSTEMI) Symptoms include crushing central chest pain/tightness or discomfort (pain may also occur in the arms, shoulders, throat, jaw, teeth, back or upper abdomen) and also breathlessness and sweating. ST elevation MI (STEMI) Pain/location/radiation is the same as NSTEMI except that it is usually (but not always) more sudden and severe, lasts longer than 30 minutes and is not relieved by rest/GTN. The pattern of symptoms in ‘unstable angina’ is characterised by frequent attacks of angina for the first time OR sudden worsening of previously stable angina OR recurrent angina at rest OR sudden onset of severe chest pain at rest. The symptoms, in contrast to STEMI, may be more likely to develop over 24-72 or more hours. Therefore an attack of angina lasting longer than 20 minutes or that keeps recurring despite repeated use of GTN requires immediate hospital admission. Other symptoms include dyspnoea, fear, pallor, sweating (clammy feeling), anxiety, vasoconstriction (peripheral) and shock. Atypical ACS symptoms may include inframammary stabbing, back pain, abdominal pain, syncope or pain free dyspnoea. Pain need not be central and may also be completely absent (silent MI). While a positive response to sublingual GTN is indicative of stable angina it should not be used exclusively to make a diagnosis. Differential diagnoses include musculoskeletal pain, pleurisy, pulmonary embolism (PE), pericarditis and gastro oesophageal reflex disease (GORD). If the pain responds to GTN within 2-5 minutes this indicates that stable angina is the probable cause. NB. GORD can respond to GTN within 5-10 minutes. Dyspnoea and sweating can still be present in PE, although unlikely with the other differentials. Patients with chest pain within the previous 12 hours should also be referred for same day assessment. Electrocardiography (ECG) In suspected ACS a resting 12-lead ECG should be performed as soon as possible (often by paramedics). Regional ST segment elevation in the leads facing the infarcted area, or new left bundle branch block (LBBB), are suggestive of STEMI and local STEMI-based treatment protocols must be followed until the diagnosis is confirmed. The development of a STEMI is represented by the following illustrations 30 6PY011 TBL: Cardiovascular System Before Event R T P Q S STEMI ST Segment elevation occurs within minutes of the occlusion occurring: After several hours the T wave inverts. The ST segment reverts to normal after several days and a Q-wave develops: Weeks afterwards the patient is left with a persistent Q-wave which indicates full thickness myocardial damage: ST Elevation = showing STEMI NSTEMI ECG signs in unstable angina and NSTEMI include regional ST-segment depression and deep T wave inversion although there may be no ECG changes. 31 6PY011 TBL: Cardiovascular System Cardiac enzymes Cardiac troponin is released from the actin and myosin complex in damaged cardiac myocytes. It is more sensitive and specific for cardiac damage than the enzymes previously used to diagnose MI: Creatine kinase MB(CK-MB), Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST) Troponin Troponin is the preferred biochemical marker for diagnosing acute MI. Cardiac troponin I or troponin T levels should be taken at initial assessment and then again 10-12 hours post onset of chest pain because troponin is released gradually towards its peak over that period (6-12 hours). Troponin I is detectable for 7-10 days post event whereas troponin T may be detected for 7-14 days. Normal levels (cTn I <0.1ng/ml; or cTn T<0.01ng/ml) occur in unstable angina but rise greater than twice the upper limit of normal in non-Q wave MI (without subsequent development of new Q-waves on the ECG). This indicates that myocardial damage has occurred but does not extend through the full thickness of the myocardium. The rise in troponin level is lower than that seen in ST elevation MI. For troponin I the limits are: Low risk of MI: Medium risk of MI: High risk of MI Troponin I level <0.1microgram/L Troponin I level 0.1-0.6 microgram/L Troponin I level >0.6 microgram/L A new marker Troponin T (HS) offers even higher sensitivity with the following limits: <14ng/L = Normal 14 to <100ng/L = consistent with myocardial damage =>100ng/L = supports the diagnosis of MI The advent of the high sensitivity troponin test has made the distinction between NSTEMIs and Unstable Angina much more accurate (see table below). This method gives improved early detection and intervention for those with confirmed NSTEMI and conversely allows NSTEMI to be ruled out within 4 hours meaning a shorter inpatient stay for those without raised levels. Sub-classifications of ACS Sub-classifications of ACS Troponin negative ACS (previously classified under unstable angina) Troponin positive ACS (previously classified under unstable angina) Non-ST elevation MI (NSTEMI) ST-Elevation MI (STEMI) ECG changes No ECG changes, T wave inversion, ST depression or transient ST elevation, bundle branch block No ECG changes, T wave inversion, ST depression or transient ST elevation, bundle branch block T wave inversion, ST depression or transient ST elevation, bundle branch block Persistent ST elevation with subsequent Q-wave Troponin I levels Nil (or Troponin T (HS) <14ng/L) <0.1ng/ml Troponin T (HS) 14- <100ng/L = consistent with myocardial damage but not classified as an MI) 2x 0.1ng/ml or =>100ng/L for Troponin HS) >0.1mg/ml or =>100ng/L for Troponin HS) (usually raised in great excess) N.B. The last two constitute an MI due to the significantly raised cardiac marker levels. Further information on the assessment of people presenting with acute chest pain can be found in NICE Guideline CG95: Chest pain of recent onset: assessment and diagnosis [ https://www.nice.org.uk/guidance/CG95/chapter/1Guidance#people-presenting-with-acute-chest-pain ] 32 6PY011 TBL: Cardiovascular System Management of ACS The following NICE ACS pathways overview provides details of the various approaches which should be adopted for the different ACS diagnoses: Overview | Acute coronary syndromes | Guidance | NICE available at: https://www.nice.org.uk/guidance/NG185 Very important: please see the visual summaries on STEMI, unstable angina NSTEMI, and secondary prevention. STEMI - Myocardial Infarction with ST-segment elevation Patients presenting with chest pain and ST-segment elevation are in an immediately life-threatening situation since complete occlusion of a major branch of a coronary artery can cause full thickness myocardial necrosis within minutes to tens of minutes. Such patients may go into VF (ventricular fibrillation) requiring the use of a defibrillator. The overall aims for STEMI management and the drugs principally used to address them can be summarised as follows: 1. Provide initial supportive care/pain relief (oxygen, nitrates, strong opioids) 2. Promote reperfusion/reduce mortality (aspirin, PCI, thrombolytic drugs) 3. Reduce re-occlusion and systemic embolization (anticoagulants) 4. Reduce mortality further (aspirin, beta-blocker, ACEI, statin) Rapid reperfusion of the affected part of the myocardium with oxygenated blood can be achieved with either Percutaneous Coronary Intervention (PCI) to restore vessel patency or the use of thrombolytic drugs to lyse the offending clot. PCI Primary PCI is the most effective way to re-vascularise a patient with STEMI. Other advantages include an absence of risk of intracranial haemorrhage and anaphylaxis (that is associated with thrombolytic drugs); shorter hospital stays; and reduced re-infarction risk. However, the procedure must be performed promptly with a minimum “door to balloon time” of 120 minutes of when PCI could have been given; and who present within 12 hours of the onset of symptoms. The following video describes the process of PCI which involves balloon angioplasty to restore vessel patency and then stenting to maintain it: https://www.youtube.com/watch?v=I45kJJoCa6s Stenting, however, is not a panacea. Overgrowth of intimal cells may lead to restenosis in 20% (or more) of cases. This can be reduced to single percentage figures by coating the stent in an anti-proliferative agent such as sirolimus or paclitaxel. Unfortunately, however, these impregnated stents delay the endothelialisation process (which will require longer-term dual oral antiplatelet therapy). It used to be considered an option also in stable angina. In 2018, NICE has changed its recommendations to say that PCI is no longer recommended in stable angina that is managed satisfactorily with medication. The angioplasty and stenting procedure exposes the subendothelial layer which is thrombogenic. Because of this, glycoprotein IIb/IIIa inhibitors (GPIs) plus either unfractionated heparin or a LMWH should be used adjunctively. Alternatively, Bivalirudin can be used instead of GPI plus antithrombotic. PCI is particularly useful for patients who have contraindications to thrombolysis and/or who are high risk patients who should receive it even if door to balloon time is greater than 90 minutes. It is only available in certain centres or on grounds of most need. An important contraindication to PCI is known allergy to contrast media (with anaphylaxis). Long-term management of patients who have undergone PCI and stenting involves the use of dual oral antiplatelet therapy. Durations of prescribing and the drugs used depends upon the circumstances around which the stent was placed e.g. elective PCI (for a stable angina patient for example) versus primary PCI, and whether bare metal or drug eluting stents are used. 33 6PY011 TBL: Cardiovascular System The BNF section on antiplatelet drugs provides details of the various dual antiplatelet prescribing pathways post PCI. Thrombolysis (or fibrinolysis) You should refer back to the 5PY022 CVS TBL pack and re-read the section on these agents. Streptokinase is extracted from streptococcal bacteria whereas synthetic tissue plasminogen activators such as reteplase, alteplase and tenecteplase are manufactured using biotechnological processes (recombinant DNA technology). Thrombolytic drugs are given to patients with ST-elevation (especially anterior) or new LBBB (unless contraindicated) presenting within 12 hours of the onset of chest pain if primary PCI cannot not be delivered within 120 minutes of the time when fibrinolysis could have been given. They are administered alongside unfractionated heparin a LMWH or fondaparinux. Timing is more important than choice of agent. The benefits of early thrombolysis are greatest if administered be within one hour of chest pain, or early (within the first 3 hours), and there is good evidence of benefit for up to 6 hours after which irreversible tissue damage occurs. Nevertheless there is still some evidence of benefit for up to 12 hours. Thrombolytics are unsuitable in patients suffering recent haemorrhage e.g. in trauma, surgery, (including dental) within last three months, in patients with coagulation disorders and or cerebrovascular disease (stroke, TIAs). They are also contraindicated in active bleeding (peptic ulcer disease, heavy menses, oesophageal varices), severe liver disease and pregnancy. Streptokinase (SK) is a significantly cheaper agent but antibodies to it are produced in patients who have previously received it. This renders any subsequent administrations ineffective. Furthermore any re-administration of SK beyond 4 days of a first dose is considered a re-challenge. Previous allergic reaction to SK/anistreplase; very low BP; and recent streptococcal infection are also contraindications. Side-effects of thrombolytics include bleeding, nausea and vomiting, low BP (especially SK which can be addressed by raising the patient’s legs or slowing the infusion rate), and anaphylaxis/allergy. The overall management of STEMI patients is outlined in the NICE pathway for STEMI: Overview | Acute coronary syndromes | Guidance | NICE available at: https://www.nice.org.uk/guidance/ng185 And the Visual summaries on STEMI treatment. Using the relevant BNF section (Acute Coronary Syndromes: ST-segment elevation myocardial infraction (STEMI) see https://bnf.nice.org.uk/treatment-summary/acute-coronary-syndromes.html make notes on both the initial and long-term management of STEMI in the box below and compare them with the NICE pathway for STEMI. Ensure that the aims/rationales for using the various treatments are clear: 34 6PY011 TBL: Cardiovascular System Initial management of STEMI (please consider oxygen, analgesia, antiplatelet (including aspirin, clopidogrel, prasugrel, ticagrelor) and antithrombotic drugs (including with PCI (and adjunctive treatments) or thrombolysis), nitrates, beta-blockers, ACE inhibitors and also insulin: Long-term management of STEMI (please consider the classic “post MI drugs” oral antiplatelet agents (or warfarin if applicable) [how does their use differ from NSTEMI/ and Unstable Angina], beta-blockers [or alternatives], statins, ACE inhibitors and also nitrates and eplerenone): 35 6PY011 TBL: Cardiovascular System Unstable Angina and NSTEMI (early management) – for patients without ST-segment elevation Initial provision of information will include details of possible causes of their symptoms, the investigations required (and associated risks) etc. A primary aim of the early management of non-ST elevation ACS is to prevent progression to a full STEMI and so the treatments used focus heavily around this. Initial treatment consists of antiplatelet and antithrombin; The rationale for this therapy is to prevent any further platelet aggregation and thrombus formation (or extension of an existing thrombus). Initial antiplatelet therapy includes 300mg loading dose of aspirin (or 300mg of clopidogrel if allergy to aspirin) Initial antithrombin (anticoagulant) therapy - Fondaparinux unless high bleeding risk or immediate angiography (within 24 hours) This is because antiplatelet and antithrombin therapies are also used as adjuncts to Percutaneous Coronary Intervention (PCI - involving balloon angioplasty and stenting) which the patient may require. Consider unfractionated heparin as initial antithrombin treatment with dose adjusted to clotting function if creatinine above 265 micromoles/litre. If patient has high bleeding risk (advancing age, bleeding complications, renal impairment, low body weight), dose and choice of antithrombin treatment needs to be reviewed. NICE has also approved Ticagrelor as an alternative to clopidogrel in NSTEACS. Risk assessment is performed using an established scoring system that predicts 6-month mortality such as GRACE (Global Registry of Acute Cardiac Events). The risk assessment includes a clinical history, physical examination, 12lead ECG and blood tests). Unlike GRACE, TIMI (Thrombolysis in Myocardial Infarction) can be calculated without accessing an online calculator (such as Grace score available at: https://www.mdcalc.com/calc/1099/grace-acs-riskmortality-calculator ) and is scored using the following risk factors: o o o o o o o Age 65 years or over Known CAD with stenosis >50% at angiography 3 or more CAD risk factors Pre event aspirin use in the last 7 days Severe angina (2 events in the last 24 hours) ST segment changes of >0.5mm Elevated troponin High risk status is associated with >3 TIMI risk factors. Conversely the GRACE score provides percentage rate figures for predicted 6-month mortality and can be readily applied to NICE guidelines. GRACE calculated risk status is attributed to the categories: lowest; low; intermediate; high and highest. The committee agreed that this should influence the choice between early invasive intervention (coronary angiography, with PCI if indicated) and conservative management (initial medical management, proceeding to coronary angiography and PCI if there is evidence of recurrent ischaemia). 36 6PY011 TBL: Cardiovascular System Please visit the following treatment summary: https://www.nice.org.uk/guidance/ng185/resources/visual-summary-unstable-angina-nstemi-pdf-8900622109 In addition to the above all patients with an MI should have their left ventricular function assessed since myocardial damage can precipitate this leading to acute heart failure. For people with unstable angina or NSTEMI who are having coronary angiography, offer: • prasugrel or ticagrelor, as part of dual antiplatelet therapy with aspirin, if they have no separate indication for ongoing oral anticoagulation. • clopidogrel, as part of dual antiplatelet therapy with aspirin, if they have a separate indication for ongoing oral anticoagulation. [2020] Management when PCI is not indicated Consider conservative management (initial medical management, proceeding to coronary angiography and PCI if there is evidence of recurrent ischaemia) without early coronary angiography for people with unstable angina or NSTEMI who have a low risk of adverse cardiovascular events (predicted 6-month mortality 3.0% or less). [2020] Offer ticagrelor, as part of dual antiplatelet therapy with aspirin, to people with unstable angina or NSTEMI when PCI is not indicated, unless they have a high bleeding risk. [2020] Consider clopidogrel, as part of dual antiplatelet therapy with aspirin, or aspirin alone, for people with unstable angina or NSTEMI when PCI is not indicated, if they have a high bleeding risk. [2020] Patients at intermediate, high or highest risk should receive a loading dose of clopidogrel in addition to aspirin. For these patients NICE also advises to: Offer unfractionated heparin with bailout glycoprotein IIb/IIIa inhibitor in combination with dual antiplatelet therapy to people with acute STEMI undergoing primary PCI with radial access. Consider bivalirudin with bailout glycoprotein IIb/IIIa inhibitor in combination with dual antiplatelet therapy for people with acute STEMI undergoing primary PCI when femoral access is needed. 37 6PY011 TBL: Cardiovascular System Compare the above with the recommendations given in BNF section 2.7.1 (Acute Coronary Syndromes: UA and NSTEMI - see https://bnf.nice.org.uk/treatment-summary/acute-coronary-syndromes.html and make notes in the box below. Hint: Consider also the use of oxygen; nitrates; opioids; antiemetics; and beta-blockers (or diltiazem/verapamil) and also the circumstances in which they are given. What do you consider to be the aims/rationales for using these additional treatments? Which drugs are used in long-term management and why? Hint: read the above recommended BNF section carefully in respect of UA/NSTEMI long-term management and ‘Prevention of Cardiovascular Events.’ 38 6PY011 TBL: Cardiovascular System Heart Failure IMPORTANT: revision from year 2 is required before studying this section. Using your year 2 CVS TBL pack, refresh your understanding of the gross anatomy of the cardiovascular system and the heart including: • • • differences between right-sided and left-sided circulations. the roles of the arterial and venous circulations. the meaning of the terms cardiac output, stroke volume, venous return, inotropic, chronotropic, systole, diastole, blood pressure and resistance. You should also remind yourself of the effect that vessel diameter, blood viscosity and blood pressure has on arterial flow. Remember, in particular, the two equations: CO = HR x SV and SV ∝ Contractility x End Diastolic Volume Peripheral Resistance …where contractility equates to the force of contraction by the heart pump, end diastolic volume equates to the preload/venous return and peripheral resistance equates to the afterload. Next, go over last year’s pack’s section on Heart Failure, including definition; points of interest and terms; clinical syndromes of heart failure; aetiology; pathophysiology; and signs and symptoms. Follow this will a review of the subsequent sections on ACE inhibitors, β-adrenoceptor antagonists, diuretics, cardiac glycosides and dobutamine and the table which examines commonly used drugs used in heart failure. The section on ACE inhibitors and the renin angiotensin aldosterone system (RAAS) covered in the hypertension section is also particularly relevant. You will need to have a good understanding of all of the above before you can go on to consider how heart failure is diagnosed and how patients are managed. You may find the following video useful: https://www.youtube.com/watch?v=7uPuhWi7KiE (Bear in mind when watching the video that, as the RAAS is activated, angiotensin II has a vasoconstrictor action which has the effect of increasing the afterload that the heart has to pump against. In addition, the increased levels of aldosterone cause sodium and then water retention which has the effect of increasing the preload. Increasing 39 6PY011 TBL: Cardiovascular System both preload and afterload, while addressing the problem of reduced CO in the short term, has the effect of exacerbating the spiralling decline that occurs in HF). Signs, symptoms and classification Symptoms and signs arise as a result of inadequate tissue perfusion, venous congestion (peripheral and pulmonary) and disturbances in water and electrolyte balance as follows: • Pulmonary congestion: breathlessness, basal crackles, frothy sputum (?tinged red), PND, orthopnoea (pillows), gasping, seeks fresh air. • Peripheral congestion: Pitting ankle oedema, raised JVP, hepatomegaly, ascites, bowel oedema, anorexia. • Reduced perfusion: Fatigue, confusion/slowness of thought, pallor, renal failure, tachycardia, cold hands & feet. • Also: 3rd/4th Heart sounds, displaced apex beat, murmurs, cardiomegaly. The New York Heart Association (NYHA) classifies HF based on symptoms and exercise tolerance and is frequently used in clinical trials which inform decisions on which patients will benefit from specific treatments: Class I No limitation during normal physical activity. Class II Slight limitation on moderate exertion e.g. walking/climbing stairs. Class III Marked limitation. Symptoms occur on minimal exertion e.g. walking on the flat. Class IV Breathlessness at rest. NICE Pathways cover the diagnoses and management of both acute and chronic heart failure as follows: Overview | Acute heart failure: diagnosis and management | Guidance | NICE Overview | Chronic heart failure in adults: diagnosis and management | Guidance | NICE This pack will focus on chronic heart failure with reduced ejection fraction and its management; which is also covered by relevant 2018 NICE Guidelines ( https://www.nice.org.uk/Guidance/NG106); and summarised in the 2019 NICE CKS for Chronic Heart Failure: Confirmed Heart Failure with Reduced Ejection Fraction (https://cks.nice.org.uk/heart-failure-chronic#!scenario) In order to make a diagnosis and to inform management various investigations may be performed: 40 6PY011 TBL: Cardiovascular System • Systems review/physical examination and routine observations: including manifestations of peripheral or pulmonary oedema or poor perfusion including abdominal examination; heart sounds, JVP, pulse and BP measurement; exercise tests (for classification); spirometry/peak flow measurements to rule out respiratory diseases. • Chest X-ray: Reveals pulmonary oedema, cardiomegaly and pleural effusion. • Echocardiography: to ascertain the ejection fraction (EF) which will be impaired in a patient with diastolic dysfunction. EF<45% is found in symptomatic heart failure. EF<35% is classified as systolic failure. • ECGs: may detect arrhythmias and previous MIs (Q-waves, LBBB) which could have been precipitating causes. • Blood: Blood gas analysis, U&Es including creatinine, LFTs, FBC (to rule out anaemia as a cause/contributory factor), TFTs (to rule out hyperthyroidism as a cause/contributory factor). Note that routine biochemistry/haematology is usually unaffected in mild-moderate HF although renal and liver function can eventually become compromised. These analyses are also required to monitor the drugs which are used in HF. Troponins may also be modestly raised. • Natriuretic peptides: raised levels occur in HF. ANP is mainly secreted from the atria and has natriuretic, diuretic and vasodilatory properties. BNP is secreted predominantly from the ventricles and has actions similar to ANP. In patients with heart failure levels of ANP and BNP are elevated due to myocardial wall stress. Plasma BNP levels tend to rise with NYHA class and can be indicative of prognosis. Note that serum levels of natriuretic peptides can be reduced in black patients, obese patients and with use of diuretics, ACE inhibitors, ARBs, beta blockers and mineralocorticoid receptor antagonists. Other non-heart failure causes of high natriuretic peptide levels include age over 70 years, left ventricular hypertrophy, ischaemia, tachycardia, right ventricular overload, hypoxaemia, renal dysfunction, COPD, diabetes and liver cirrhosis. Patients with a history of previous MI should be referred for echocardiography and those without previous MI should have serum natriuretic peptides measured. Differential diagnoses There are many conditions that can present with similar symptoms to heart failure. These include obesity, chest disease – including lung, diaphragm or chest wall, venous insufficiency in lower limbs, drug-induced ankle swelling (e.g. due to dihydropyridine calcium channel blockers), drug-induced fluid retention (e.g. due to NSAIDs), hypoalbuminaemia, intrinsic renal or hepatic disease, pulmonary embolic disease, depression and/or anxiety disorders, severe anaemia or thyroid disease and bilateral renal artery stenosis. The above investigations will assist in ruling out many of these. 41 6PY011 TBL: Cardiovascular System Management of chronic heart failure Because of the spiralling decline the aims of management adopt the following focus: 1. 2. 3. 4. Reduce mortality. Delay disease progression/reduce exacerbations. Control symptoms. Improve quality of life/exercise tolerance. Treatments for HF address the first two aims, in particular. Non-pharmacological management This includes consideration of exercise (cardiac rehabilitation programmes for stable patients), smoking status and alcohol consumption. Patients should be monitored for signs of depression which may develop. They should not be routinely advised to restrict sodium and fluid intake but potassium containing salt substitutes should be avoided. Pharmacological management *****IMPORTANT ***** Before you consider the management of chronic heart failure you should look back carefully at the year 2 cardiovascular system study pack at the pathophysiology and presentation of heart failure. You should fully understand ✓ the long-term impact of increased preload and afterload including the compensatory activation of the RAAS and why this causes the spiralling decline; ✓ why (and how and where) fluid overload develops when either side of the heart fails; ✓ the differences between diastolic and systolic failure; ✓ how poor perfusion of blood to the tissues and organs manifests itself; ✓ and how the various classes of drugs used in heart failure management address these pathophysiological problems. Pharmacological management of CHF patients with LVSD is well established, especially the use of those agents which aim to reduce the spiralling decline whereas treatment options for patients who have preserved ejection fraction is limited to symptomatic options e.g. loop diuretics. First line pharmacological treatment involves the use of ACE inhibitors (or AII antagonists if not tolerated) and a beta-blocker in all classes of heart failure. A key aspect which pharmacists should be aware of and support involves careful titration to the maximum licensed dose in heart failure (or the highest licensed dose tolerated). If neither are tolerated a specialist may initiate a combination of an oral long acting nitrate and hydralazine to decrease the preload and afterload respectively ACE inhibitors should be initiated progressively with an escalating dose pattern over 1-2 months due to the risk of first dose hypotension which is especially problematic in patients taking loop diuretics because of the risk of inducing dangerous hypovolaemia which can lead to cardiac arrest. In patients who are intolerant to ACEIs, or for whom there are contraindications, an angiotensin receptor blocker may be used.. Beta-blockers can precipitate pulmonary oedema and so should be up-titrated slowly and cautiously over several weeks or months. It may be necessary to either step back down periodically or use loop diuretics to address oedematous symptoms in order to support the dose titration. However, aim for the highest dose of Beta blocker and ACE inhibitor the patient can tolerate. Beta-blockers should not be withheld solely because of age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease or chronic obstructive 42 6PY011 TBL: Cardiovascular System pulmonary disease. Patients already taking beta-blockers and who are stable should be switched to a beta-blocker licensed for HF. Use your BNF to establish which ACEIs, AII antagonists and beta-blockers are licensed for heart failure. Note which beta blockers on your list have cardioselectivity. ACEi’s AII receptor antagonists Beta - blockers The mineralocorticoid receptor antagonist spironolactone antagonises aldosterone and can be added to the above in patients who remain symptomatic. Eplerenone may be used as an alternative, especially in post MI patients. It became common practice a few years ago to use ACEI inhibitors in combination with AII antagonists, in an attempt to minimise side effects, however as an example of how evidence continually informs practice, the BNF now states: “Combination therapy with two drugs affecting the renin-angiotensin system (ACE inhibitors, angiotensin-II receptor antagonists, and aliskiren is not recommended due to an increased risk of hyperkalaemia, hypotension, and renal impairment, compared to use of a single drug.”ACEi may also be used as second line treatment or in combination with the recently marketed sacubitril valsartan. Ivabradine is also licensed for use in patients as an additional option for symptomatic patients (or as an alternative to beta-blockers where contraindicated) who have a pulse of => 75 bpm. It should be initiated under specialist supervision in patients who have been stable on optimised standard therapy for at least 4 weeks. Furthermore sacubitril valsartan has also been approved by NICE as a specialist option for patients with symptomatic chronic heart failure with reduced ejection fraction (NYHA classes II-IV; EF <= 35%) who are taking a stable dose of an ACE inhibitor or ARB. It used to be believed that Digoxin has no effect on mortality, but the latest evidence suggests this is wrong. It can used for the symptomatic treatment of patients who are already taking the above treatments. Its narrow therapeutic window with a risk of serious toxicity and its susceptibility to drug interactions must be taken into account, especially when prescribed with diuretics. Fluid overloading requires the use of diuretics, normally as more potent loop diuretic which are ‘high ceiling’ with which higher doses produce more diuresis. Thiazide diuretics are ‘low ceiling’ agents that produce more adverse effects without increases in potency beyond a certain limit. While 2.5mg of bendroflumethiazide may be used in patients with mild heart failure, those who require the addition of a thiazide to a loop diuretic such as furosemide tend to be given metolazone. Careful daily body weight and fluid balance (input/output) monitoring is required to avoid rapid loss of fluid which can precipitate hypovolaemia. A loss of 0.5-1Kg of fluid per day is typical of the cautious approach that is required. IV furosemide is usually required due to the presence of gut oedema since the oral preparations are not well absorbed by the oedematous gut, limiting its clinical effect. The SGLT2 inhibitors Dapagliflozin and Empagliflozin have recently been recommended as options for treating symptomatic chronic heart failure with reduced ejection fraction in adults. Their effects include improved cardiac metabolism, reduced inflammation, reduced cardiovascular death and reduced hospitalisations due to heart failure. Patients with underlying atherosclerotic arterial disease should be considered for antiplatelet and statin therapy; and all co-morbidities and precipitating factors should be managed e.g. asthma, COPD, angina, atrial fibrillation, valve disease, gout and diabetes. Calcium-channel blockers should be avoided in heart failure with reduced ejection fraction; and patients with HF should receive annual influenza and once-only pneumococcal vaccinations. 43 6PY011 TBL: Cardiovascular System Complete the following drugs table using the heart failure section 2.5 and relevant monographs in the BNF: HINT: Use a combination of the BNF sections covering the relevant drug classes and clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ to help you find the MOST IMPORTANT cautions, contraindications, side effects, monitoring, interactions and counselling. Key cautions* and Key adverse contraindications** effects AND monitoring Important interactions Other notes and counselling ACE Inhibitors AII Antagonists Sacubitril-Valsartan Beta-blockers Spironolactone Digoxin Furosemide Bendroflumethiazide Dapagliflozin 44 6PY011 TBL: Cardiovascular System Arrhythmias You will recall from your learning in the 5PY022 CVS study pack that an arrhythmia is any condition where there is abnormal electrical activity of the heart. The heart rate can be too fast (tachycardia), too slow (bradycardia), regular or irregular. The pathophysiology of arrhythmias and the pharmacology/pharmaceutics of the drugs used in their management have already been covered and you may wish to now take some time to go through your notes from last year to familiarise yourself before beginning this section. Presentation A patient with an arrhythmia may present with the following signs and symptoms: • • • • • • • Dizziness. Palpitations. Chest pain. Fatigue. Syncope. Shortness of breath (dyspnoea). Rarely, and in extreme cases, collapse and cardiac arrest. However, some patients with an arrhythmia may have no symptoms. Diagnosis Patients who present with any of the above symptoms or with a stroke or transient ischaemic attack should be investigated for the presence of an irregular pulse. Firstly, a manual pulse palpation should be performed to assess the heart rate and for the presence of an irregular pulse that could indicate an underlying arrhythmia. If an arrhythmia is suspected then an electrocardiogram (ECG) should then be performed. An ECG records the rhythm and electrical activity of the heart. During the ECG electrodes are placed on the patient’s arms, legs and chest, these are connected to the ECG recording machine by wires. The recording machine picks up the electrical signals from the heart and then this is recorded and printed onto paper. If required, a 24-hour continuous ECG can be performed. This can be useful if the patient is suffering from palpitations that don’t occur continuously. The following video provides basic information on electrocardiography: https://www.youtube.com/watch?v=HDyqXNHLjug Non-pharmacological Treatment Non-pharmacological treatment can be split into 3 categories.    Electrical strategies. Pacing strategies. Ablation therapies. Electrical Therapies – Direct Current Cardioversion This restores normal heart rhythm. Cardioversion can be done pharmacologically with medications such as amiodarone but is also commonly done via electric shock. Prior to the procedure patients will need to be anticoagulated to prevent thromboembolism. Patients are anaesthetised or receive heavy sedation immediately 45 6PY011 TBL: Cardiovascular System before. The procedure consists of an electric shock administered across the chest wall. This overrides disordered conduction and allows the sinoatrial (SA) node to regain control. The procedure is not always successful, especially in the elderly, those with long-standing atrial fibrillation (AF), mitral valve disease or cardiomyopathies. Some patients may still need long term pharmacological therapy to prevent recurrent episodes of arrhythmias. Please note that although it appears to be the same, cardioversion is different to defibrillation, which is given when someone is having a cardiac arrest. The following video from the British Heart Foundation explains what happens during a cardioversion procedure: https://www.youtube.com/watch?v=zC7yVk4yklA Pacing Strategies – Pacemakers These are used for patients with bradyarrhythmia’s. The pacemaker is inserted into a ‘skin pocket’ below the collar bone. Leads are inserted into the heart, positioned under x-ray guidance. The leads sense electrical activity in the heart to assess rate and rhythm. The pacemaker delivers ‘when required’ electrical impulses to the myocardial tissues via the leads to generate an action potential and stimulates contraction. The following video deals with pacemaker implantation: https://www.youtube.com/watch?v=DHJT9eJXHLI Pacing Strategies - ICDs An ICD is an internal cardioverting defibrillator that is implanted into high risk patients to prevent sudden cardiac death from tachyarrhythmias. Similar to a pace maker it monitors for rate and rhythm. If the ICD senses a ventricular tachycardia (VT) it delivers pacing impulses at a very fast rate to regain control of the heart rhythm and then slows the rate down in a controlled manner. If this fails then the device will deliver an electrical shock. Patients may require pharmacological treatment to minimise the number of shocks needed as they can be unpleasant. Ablation Strategies – Radiofrequency Ablation Firstly electrophysiological studies are carried out to map electrical activity of the heart and identify the source of the arrhythmia. A catheter with an electrode on its end is guided to the source site and then radiofrequency energy is used to destroy the tissue locally and destroy abnormal conduction pathways. This prevents future arrhythmias and the need for long term pharmacological therapy. The procedure is usually done under local anaesthetic and has a good success rate. Pharmacological Treatment Which pharmacological treatment is selected will depend on the type of arrhythmia the patient has. Pharmacological treatments are used in tachyarrhythmias to reduce the heart rate to a normal range and also get it beating back into a normal rhythm. Remember in some cases a combination of pharmacological and non-pharmacological treatment may be required. 46 6PY011 TBL: Cardiovascular System The following table shows some of the tachyarrhythmias and the pharmacological treatments that can be considered. Tachyarrhythmia Sinus tachycardia Sinus node re-entry tachycardia Atrial tachycardia Treatment Firstly treat the underlying cause (e.g. hypotension, anaemia, hypovolaemia, PE, infection, thyrotoxicosis) and this should stop the tachycardia. If no precipitant can be found then rate controlling medications such as beta-blockers or calcium channel blockers can be used. Sometimes stops of own accord but medications such adenosine, verapamil or beta-blockers can be used to expedite it. Choice of drug depends if the patient has left ventricular dysfunction – class IA and IC antiarrhythmics are contraindicated if the left ventricle is impaired due to their proarrhythmic effects. In mild LV dysfunction sotalol can be used but amiodarone is more appropriate if the patient has moderate to severe dysfunction. Beta-blockers or rate controlling calcium channel blockers can be used to control ventricular rate. Atrial Fibrillation (AF) https://www.nice.org.uk/guidance/ng196 Atrial fibrillation is the most common arrhythmia. The aim of treatment is to alleviate symptoms and prevent complications (most notably stroke). NICE guidance will be needed for you to complete the learning activities that follow. Rate Control Pharmacological rate control can be offered as a first line strategy to patients with AF. Using NICE NG196, use the space below to list the pharmacological options NICE recommend for rate control in patients with AF. 47 6PY011 TBL: Cardiovascular System Using NICE NG196, use the space below to make a list of patients with AF who should NOT be offered rate control as a first line strategy. Rhythm Control If symptoms continue in patients who have received rate control or if rate control has been unsuccessful then rhythm control should be considered. This can be pharmacological, electrical or a combination of both. Remember cardioversion can be pharmacological or electrical. NICE recommends that patients having cardioversion for AF that has persisted for longer than 48 hours should be offered electrical cardioversion. However, NICE do recommend considering amiodarone therapy for 4 weeks before electrical cardioversion and continuing with the amiodarone for up to 12 months to maintain sinus rhythm. The benefits and risk of amiodarone should be discussed with the patient. If appropriate pharmacological treatment can be given for long-term rhythm control after assessment of the patient’s comorbidities, risks of treatment, likelihood of the AF occurring and of course, the patient’s preference. Using the BNF and SmPC as a minimum, use the space below to make notes on how amiodarone is initiated (based on its pharmacokinetcs); and also a list of the side effects of amiodarone that would need to be discussed with the patient and the monitoring that would need to be done prior to and during treatment. HINT: Use clinical pharmacy textbooks such as Whittlesea and Hodson’s ‘Clinical Pharmacy and Therapeutics’ to help you. 48 6PY011 TBL: Cardiovascular System Using NICE NG196 use the space below to summarise the drug treatment options for long-term rhythm control recommended. ‘Pill in the pocket’ Strategy For patients that have infrequent episodes of paroxysmal AF this strategy can be considered. Patients will need to be able recognise the onset of their AF symptoms and then take a tablet, usually flecainide or propafenone. Patients selected for this method of treatment should also not have any significant underlying cardiovascular disease. Assessment of Stroke Risk Condition Points C Congestive heart failure (or left ventricular systolic dysfunction) 1 H Hypertension – BP consistently above 140/90 mmHg (or treated hypertension on medication) 1 A2 Age ≥ 75 years 2 D Diabetes Mellitus 1 S2 Prior stroke or TIA or thromboembolism 2 V Vascular disease (e.g. peripheral artery disease, myocardial infarction, aortic plaque) 1 A Age 65-74 years 1 Sc Sex category - female 1 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263-72. 49 6PY011 TBL: Cardiovascular System Patients with paroxysmal, persistent or permanent AF, an atrial flutter or at a continuing risk of arrhythmia recurrence after cardioversion can be at an increased risk of stroke. NICE recommend that these patients should have their stroke risk assessed using the CHA2DS2-VASc stroke risk score. The CHA2DS2-VASc stroke risk score was developed here in the West Midlands. It calculates stroke risk based on a number of different factors, if the patient was to remain non-anticoagulated and so is used to help decide if a patient with AF should be anticoagulated. The scoring system is summarised in the table above. NICE recommends not offering stroke prevention therapy with anticoagulation to people aged under 65 years with atrial fibrillation and no risk factors other than their sex (that is, very low risk of stroke equating to a CHA2DS2-VASc score of 0 for men or 1 for women).Offer anticoagulation with a direct-acting oral anticoagulant (DOAC) to people with AF and a CHA2DS2-VASc score of 2 or above and consider a DOAC for men with AF and a CHA2DS2-VASc score of 1, taking into account the risk of bleeding. Apixaban, dabigatran, edoxaban and rivaroxaban are all recommended as options, when used in line with the criteria specified in the relevant NICE technology appraisal guidance. They recommend that the Outcomes Registry for Better Informed Treatment of Atrial Fibrilation (ORBIT-AF) scoring system is used to assess major bleeding risk and supersedes the use of HAS-BLED which had limited evidence amongst DOAC treatments. O'Brien et al devised the ORBIT bleeding risk scoring system: The ORBIT scoring should be used when assess the risk of bleeding when: considering starting anticoagulation in people with atrial fibrillation and when reviewing people already taking anticoagulation. Please see ORBIT scoring system below: Risk Factor For Bleeding Older age (75 years or older) Reduced haemoglobin (<13 mg/dl in men and <12 mg/dl in women), haematocrit (<40% in men and <36% in women) or history of anaemia Bleeding history Insufficient kidney function (GFR < 60 mg/dl/1.73 m2) Treatment with an antiplatelet agent Points Attributed 1 point 2 points 2 points 1 point 1 point ORBIT Score Risk group 0-2 3 4-7 Low Medium High Bleeds per 100 patientyears 2.4 4.7 8.1 Interpretation: A score above 4 does not mean that anticoagulation should not be used but that careful clinical judgment is needed and the patient will need regular clinical follow up and monitoring. Some of the risk factors for bleeding are also reversible, for example blood pressure can be controlled with antihypertensive agents and NSAIDs or antiplatelet agents could be discontinued after review. Reduced haemoglobin/anaemia was most strongly associated with major bleeding, followed by bleeding history, treatment with antiplatelets, insufficient kidney function, and older age. 50 6PY011 TBL: Cardiovascular System Read the following article from Professor Lip and his team that discusses how they used scoring tools to decide whether they should anti-coagulate a patient. • Lane DA, Lip GYH. Use of the CHA2DS2-VASc and HAS-BLED Scores to Aid Decision Making for Thromboprophylaxis in Nonvalvular Atrial Fibrillation. Circulation. 2012; 126: 860-865 http://circ.ahajournals.org/content/126/7/860.full Choice of Anticoagulation NICE recommends that anticoagulation can be with apixaban, dabigatran, rivaroxaban or edoxaban. If direct-acting oral anticoagulants are contraindicated, not tolerated or not suitable in people with atrial fibrillation, offer a vitamin K antagonist such as warfarin (NICE NG196). NICE has produced technology appraisals for apixaban, dabigatran, rivaroxaban and edoxaban that are available on their website. Note also that the MHRA has issued a warning about bleeding risk with DOAC use, and details of the availability of reversal agents. https://www.gov.uk/drug-safety-update/direct-acting-oral-anticoagulants-doacs-reminder-of-bleeding-riskincluding-availability-of-reversal-agents Using NICE NG196 and the NICE technology appraisals, use the space below to summarise when use of each of the anticoagulants above is recommended for us for prevention of stroke in AF. Apixaban Dabigatran Rivaroxaban Edoxaban Warfarin 51 6PY011 TBL: Cardiovascular System Pharmacists’ Roles in Arrhythmia Management As experts in medications pharmacists are well placed to advise on which medications can be used for rate and/or rhythm control depending on the type of arrhythmia the patient has. They can also advise on drug interactions and cautions and contraindications and of course provide counselling to patients on their new medication to help improve compliance and concordance. One area pharmacists can be particularly useful in is reviewing patients with a diagnosis of AF to assess their stroke risk and ensure they are offered anticoagulation if appropriate for them. Counselling on anticoagulant medications is also very important to ensure safe and effective use. Revisit your notes from last year to ensure you feel confident in counselling patients on anticoagulants. A review team in Yorkshire that was led by pharmacists reviewed patients with AF and lead to a large number patient have their medication optimised and a large number of patients being started on appropriate anticoagulant treatment. This review scheme is estimated to have prevented 886 strokes and £22 million in costs to the NHS. You can read more about it at the following link: https://pharmaceutical-journal.com/article/news/pharmacist-led-atrial-fibrillation-reviews-reduce-stroke-risk-forpatients Venous Thromboembolism (VTE) You will have learnt about the pathophysiology of VTE and the pharmacology of the drugs used to prevent and treat VTEs in the CVS study pack in 5PY022 last year. You may wish now to revisit your notes before continuing with this section. This year we will look at how to prevent VTE, how to diagnose VTE and how to treat VTE. Prevention of VTE Back in 2005 it was reported that an estimated 25,000 people in the UK die from preventable hospital acquired VTE every year and that there was an inconsistent approach of preventing this. This was not good enough and since then there has been a big push in hospitals to ensure patients are properly assessed on admission to hospital, in fact it is now mandatory that all patients should receive a VTE assessment if they are admitted to hospital for any reason. NICE has published guidance on prevention of VTE in hospital patients, which is available here: https://www.nice.org.uk/guidance/ng89 You should familiarise yourself with this guidance and use it to help complete the learning activities in this section. Risk factors for VTE were covered in your CVS 5PY022 study pack. Using this and NICE NG89, use the space below to record the risk factors for VTE in patients admitted to hospital. 52 6PY011 TBL: Cardiovascular System As well as assessing patients for risk of VTE, they should also be assessed for their bleeding risk as pharmacological VTE prophylaxis will increase the risk of major bleeding in these patients. Using NICE NG89 risk the risk factors for bleeding. After the initial admission assessment patients should be reassessed again with 24 hours of admission and also if their clinical situation changes. This ensures that they are on a suitable method or methods of VTE prophylaxis that is being used correctly and also to identify any adverse events. To reduce the risk of VTE whilst in hospital patients should be well hydrated and encouraged to mobilise as soon as they can. VTE prophylaxis can be non-pharmacological or pharmacological. Depend on the level of risk a combination of the two may be used. Non-pharmacological VTE prophylaxis This includes: • • • Anti-embolism (compression) stockings. Foot impulse devices. Intermittent pneumatic compression devices. Stockings should not be used in certain patients. This includes patients with peripheral arterial disease, local skin conditions that could be exacerbated, cardiac failure, severe oedema or if the patient has been admitted with a stroke. 53 6PY011 TBL: Cardiovascular System Pharmacological VTE prophylaxis Pharmacological VTE prophylaxis should be offered to patients assessed to be at increased risk after their bleeding risk has also been taken into consideration. NICE recommend that this can be with fondaparinux, a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) infusion. Hospitals will have their own local guidelines on what pharmacological VTE prophylaxis should be used. The most used is a LMWH, these have the advantage of being a once daily administration, do not require anticoagulant monitoring and have a lower risk of heparin-induced thrombocytopenia. The dose of LMWH used for prophylaxis is a low dose and higher doses are used for actually treating a VTE or for treating ACS. As the dose varies by indication and also by which LMWH is being used the BNF or SPC should be consulted for advice. Heparin in comparison to LMWH has to be given via a continuous infusion and requires anticoagulant monitoring. Some patients who have had certain types of surgery may require VTE prophylaxis for a period of time after their surgery as their mobility will be reduced and so their increased risk will continue, this may mean they are discharged on the treatment to continue using at home. Using NICE CG92 and the BNF complete the following table for the different types of surgery. The first row is completed for you as an example: Type of surgery Elective hip replacement Length of VTE prophylaxis after surgery 28-35 days (depending on SPC of medication used) Pharmacological treatments that can be used LMWH, fondaparinux, UFH, rivaroxaban, dabigatran, apixaban Elective knee replacement Hip fracture surgery Other orthopaedic surgery Vascular surgery Patients who have major abdominal surgery or a caesarean section are also at increased risk of VTE post-surgery and are given a course of thromboprophylaxis. Diagnosis of VTE As a recap from last year let’s remind ourselves of the signs and symptoms of VTE a patient may present with. This is particularly important as a patient may present with one or more of these symptoms to a community pharmacy and the pharmacist would be responsible for recognising that the patient could be suffering with a VTE and to refer them on to urgent care. 54 6PY011 TBL: Cardiovascular System The symptoms of a deep vein thrombosis (DVT), which usually occur in a leg, include: • • • • Pain, swelling and tenderness in one leg (usually in the calf). Increase in skin temperature in the affected area, skin can be hot to the touch. Redness of the skin. Heavy ache in the affected area. The symptoms of a pulmonary embolism (PE) include: • • • • Chest pain that is usually described as sharp or stabbing. Shortness of breath (dyspnoea). Coughing up blood (hematemesis). Faintness. Diagnosis of DVT NICE have produced guidance on the diagnosis and management of thromboembolism, which is available as part their CG144: Venous thromboembolic diseases: diagnosis, management and thrombophilia testing, available online at: https://www.nice.org.uk/guidance/ng158 When a patient presents with symptoms of a DVT their history is taken alongside a physical examination to exclude other causes. If there is a suspicion of a DVT then the two-level DVT Wells score is used to estimate the clinical probability of a DVT. The two-level DVT wells score is shown below: Clinical Feature Points Active cancer (treatment ongoing, within 6 months, or palliative) 1 Paralysis, paresis or recent plaster immobilisation of the lower extremities 1 Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia 1 Localised tenderness along the distribution of the deep venous system 1 Entire leg swollen 1 Calf swelling at least 3 cm larger than asymptomatic side 1 Pitting oedema confined to the symptomatic leg 1 Collateral superficial veins (non-varicose) 1 Previously documented DVT 1 An alternative diagnosis is at least as likely as DVT −2 Taken from NICE NG158. Original reference: Scarvelis D, Wells P (2006). "Diagnosis and treatment of deep-vein thrombosis". CMAJ. 175 (9): 1087–92 A DVT is likely if the patient scores two points or more and is unlikely if the patient scores one point or less. 55 6PY011 TBL: Cardiovascular System Patients who have a likely DVT should then be offered a proximal leg vein ultrasound within 4 hours. If the result is negative a D-dimer test should be carried out to further exclude a DVT. A D-dimer test is a blood test that test for the level of D-dimer, which is a fibrin degradation product that is present in the blood after a blood clot has undergone fibrinolysis. If the proximal leg vein ultrasound is not available then a D-dimer test should be performed and the patient given a dose of a parenteral anticoagulant (usually a LMWH at a treatment dose) and then the scan should be performed within the next 24 hours. Further information on different tests that can be done if the patient is unlikely to have a DVT can be found in the NICE NG158 guideline. Diagnosis of PE Patients who present with symptoms of a PE will again have their history is taken alongside a physical examination to exclude other causes and will also have a chest X-ray taken. If a PE is suspected then a two-level PE Wells score should be performed to ascertain the probability of a PE. Using NICE NG158 use the space below to document what is assessed in two-level PE Wells score. Is this different to the two-level DVT Wells score? If the patient scores more than 4 points then is likely they have a PE, if they score 4 points or less then it is unlikely they have PE. If a PE is likely then the patient should receive an immediate computed tomography pulmonary angiogram (CTPA) or if this is not possible then parenteral anticoagulant therapy until a CTPA can be carried out. The CTPA is used to obtain an image of the pulmonary arteries. The patient is given an intravenous injection of contrast media and then images are taken. Normally the results would show the contrast filling the pulmonary vessels but if there is an 56 6PY011 TBL: Cardiovascular System embolus this will be blocked. Further information on different tests that can be performed if the patient is unlikely to have a PE or is unable to have a CTPA can be found in the NICE NG158. Pharmacological Treatment for DVT and PE Previously treatment for DVT and PE would initially have been a LMWH or fondaparinux and then the patient would have been started on a vitamin K antagonist such as warfarin. The parenteral treatment needs to continue until the vitamin K antagonist has achieved a therapeutic effect, this is achieved by measuring the International Normalised Ratio (INR), which you learnt about last year in 5PY022. The target INR for patients with DVT or PE is 2.5. The above treatment remains an option for treatment of DVT and PE, however as you learnt in your 5Y022 CVS study pack there are now more oral anticoagulants available. These are apixaban, dabigatran, rivaroxaban and edoxaban are also available, these are direct and reversible inhibitors of activated factor Xa. All four of these medications are licensed for the treatment and prevention of DVT and PE. With apixaban and rivaroxaban there is no need for treatment with a parenteral anticoagulant first but with dabigatran and edoxaban 5 days of treatment with a parenteral anticoagulant must be given before they are started. NICE have produced technology appraisals for apixaban, dabigatran, rivaroxaban and edoxaban and their use in DVT and PE. Find these on the NICE website and use the space below to make notes on what NICE recommends. If a patient with a PE becomes haemodynamically unstable (for example their blood pressure drops and they are unable to maintain oxygenation) then treatment with a fibrinolytic such as alteplase may be indicated. This will be on the recommendation of a specialist and the patient will need to be closely monitored. Duration of Anticoagulant Treatment When deciding on the duration of anticoagulant treatment the risk of thromboembolism and risk of anticoagulant related bleeding should be taken into consideration. The following duration of warfarin is recommended by the British Society of Haematology: • • • 6 weeks for isolated calf DVT. 3 months for VTE provoked by surgery or other transient risk factor. At least 3 months for unprovoked proximal DVT or PE; long-term anticoagulation may be required. 57 6PY011 TBL: Cardiovascular System Patient Counselling As mentioned in the arrhythmias section of this study pack it important that pharmacists feel comfortable counselling patients on anticoagulants. IMPORTANT If you haven’t already, make sure you revisit your notes about warfarin counselling from last year. It is important to remember that patients need counselling on the newer anticoagulants now available and pharmacists also need to be confident on providing information and counselling to patients taking one of these medications. Read the following article available online via The Pharmaceutical Journal Website: Bhandal S, Pattinson J. How to support patients taking new oral anticoagulant medicines. Clinical Pharmacist 2013 Clinical Pharmacist, Vol. 5, p268 | DOI: 10.1211/CP.2013.11129491, and the BNF monographs of apixaban, dabigatran, rivaroxaban and edoxaban. Use the space below to make notes on how you would counsel a patient on one of these medications. Compare this to the counselling list for warfarin that was in your 5PY022 CVS study pack. 58 6PY011 TBL: Cardiovascular System Stroke Please see the NICE guidance available at: Overview | Stroke and transient ischaemic attack in over 16s: diagnosis and initial management | Guidance | NICE (https://www.nice.org.uk/guidance/ng128) A stroke is a focal neurological deficit due to the interruption of the blood supply to the brain. It is important to understand that there are two different types of stroke – ischaemic and haemorrhagic, and that the pathophysiology and therefore treatment of each type is different. Ischaemic strokes are more common than haemorrhagic strokes. Click here to view a video of the blood supply to the brain: Also available at: Stroke is a medical emergency and the sooner it is diagnosed and treated the better the outcome will be for the patient. Photo: http://www.stroke.org.uk Signs and symptoms of a stroke are: o Facial weakness. o Arm/leg weakness. o Disturbed speech. o Visual defect. o Dizziness/fall. o Loss of consciousness. o Headache. There have been several advertising campaigns from Public Health England aimed at recognising the symptoms of stroke and prompting people to seek urgent medical attention to allow for fast treatment. The campaigns focus around the acronym ‘FAST’. Act FAST Campaign: https://www.facebook.com/NHSEngland/videos/act-fast-tvadvert/2076281909322607/ F – Face – is there a droop on one side of the face? Can the person smile? A – Arms – can the person raise both arms and keep them there? S – Speech – is the person’s speech slurred? T – Time to call 999 – if the person is displaying any of the signs 59 6PY011 TBL: Cardiovascular System Risk Factors and Epidemiology Non-modifiable risk factor Age Ethnicity Ischaemic heart disease/peripheral vascular disease Genetic predisposition (family history) Gender Sickle cell disease Modifiable risk factor Hypertension Smoking Atrial fibrillation Hyperlipidaemia Diabetes Diet, alcohol intake and exercise Stress and/or depression High waist to hip ratio High ratio of apolipoprotein B to apolipoprotein A1* *Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the circulatory and lymphatic systems. Apolipoprotein B forms low-density lipoprotein particles (‘bad cholesterol’). Apolipoprotein A1 is the major protein component of high-density lipoprotein particles (‘good cholesterol’). There are approximately 152,000 strokes per year in the UK. 1 in 8 strokes are fatal within the first 30 days and 1 in 4 are fatal within a year. Stroke is the 4th single largest cause of death in the UK. There are approximately 1.2 million stroke survivors in the UK, over half of these survivors will have disability. Stroke is the largest cause of complex disability and over a third of stroke survivors in the UK are dependent on others. Ischaemic Stroke An ischaemic stroke can be thrombotic or embolic. Thrombotic strokes are commonly the result of atherosclerosis. As the plaques grow in size, the blood vessel becomes narrowed and the blood flow to the area beyond is reduced. Damaged areas of an atherosclerotic plaque can cause a blood clot to form, which blocks the blood vessel causing an infarction in the brain. Embolic strokes occur when blood clots or debris from elsewhere in the body travel through the circulatory system. The main cause of embolic stokes is atrial fibrillation. In ischaemic strokes there is a cascade of neurochemical events that begin in the area of brain tissue supplied by the occluded vessel: • • • • • • Energy depletion followed by disruption of ion homoeostasis. Release of glutamate. Calcium channel dysfunction. Release of free radicals. Membrane disruption. Inflammatory changes. The surrounding live tissue in the brain is at risk of death but can be saved by restoration of blood supply. This is why the diagnosis and treatment of ischaemic stroke is time critical. 60 6PY011 TBL: Cardiovascular System Transient Ischaemic Attack A transient ischaemic attack (TIA) is caused by a temporary disruption in the blood supply to the brain, leading to ischaemia from lack of oxygen supply. They can be caused by a clot or other debris. It is often referred to as a ‘mini stroke’. The symptoms are the same or very similar to those of a stroke, however they are short-lived (can be a few minutes to hours) and usually fully resolved within 24 hours. In the early stages of symptom onset it is not possible to determine whether someone is suffering with a TIA or a stroke, so an immediate 999 call is still appropriate. The symptoms may resolve before the ambulance arrives, but the patient should still receive and assessment in hospital. A TIA is a warning sign that a patient is a high risk of having a full stroke in the future. Haemorrhagic Stroke Types of haemorrhagic stroke include intracerebral haemorrhage and subarachnoid haemorrhage. Haemorrhagic strokes are caused by a rupture of blood vessels that then causes a compression of brain tissue from an expanding haematoma. This results in brain tissue injury and the blood released appears to have direct toxic effects on brain tissue and vasculature. Intracerebral haemorrhage is usually caused by the rupture of small penetrating vessels in the brain. It is commonly the result of blood vessel damage from chronic hypertension or the use of medications such as anticoagulants, thrombolytics or antiplatelets. It can also be cause by physical trauma to the head. A subarachnoid haemorrhage is a gradual collection of blood within the subarachnoid space surrounding the brain. It can be cause by trauma to the head or rupture of a cerebral aneurysm. Treatment of Stroke https://cks.nice.org.uk/topics/stroke-tia/management/ The treatment aims for both types of stroke are to achieve the best possible recovery of function, to avoid secondary complications and to prevent further events (secondary prevention). In the UK, NICE recommends that every patient with a stroke should be referred to a dedicated stroke unit. Patients who are treated on such units show significantly better outcomes than patients treated in a general medical ward. NICE acute stroke pathway The key issue in ischaemic stroke is to achieve rapid reperfusion through the administration of anticoagulants, which it is obvious, would be catastrophic in a patient with a haemorrhagic stroke. It is therefore of paramount importance to distinguish between these causes as quickly as possible. This cannot be reliably achieved through clinical examination. In theory, the ‘ideal’ investigation would be Magnetic Resonance Imaging (MRI) scanning as this would provide the clearest and most detailed image, but a typical scan takes 45-60 minutes during which time, brain tissue is dying. Consequently the investigation of choice is computerised axial tomography (CAT) also known as Computerised Tomography (CT) scanning of the head. This takes only 5-10 minutes. A description of tomography findings can be found in the course textbook Whittlesea & Hodgson. 61 6PY011 TBL: Cardiovascular System Ischaemic Stroke Treatment NICE (in NG128) recommend that patients with ischaemic stroke should receive aspirin 300 mg daily for 2 weeks. This can be given orally but may also be given rectally in suppository form if the patient is unable to take medication enterally. After this clopidogrel is recommended at a dose of 75 mg daily to prevent further events. Anticoagulants are not used for secondary prevention of stroke and would only be used if indicated for another reason (e.g. venous thromboembolism or atrial fibrillation). Statins can also be given for secondary prevention. If the patient was already taking a statin prior to the stroke, this can continue but if one is to be newly initiated then it should be started at least 48 hours after the stroke. Antihypertensives should be used cautiously initially unless the patient is severely hypertensive. Patients with severe hypertension following a stroke can be given intravenous labetalol or intravenous GTN (if beta-blockers are contraindicated). For some patients it is appropriate to undergo a carotid endarterectomy, which is surgery to remove a plaque or clot from the carotid arteries or carotid angioplasty, although this procedure carries at least a 1:100 risk of a bleed (haemorrhagic stroke) post-operatively. Secondary Prevention of TIA Patients who suffer with a TIA should receive treatment and advice to prevent another TIA or a full stroke occurring in the future. NICE recommend treatment as per secondary prevention of stroke: Antiplatelet therapy is initiated by secondary care on diagnosis of ischaemic stroke or TIA without paroxysmal or permanent atrial fibrillation for long-term vascular prevention: • • • • • The standard treatment is clopidogrel 75mg daily (licenced for use in ischaemic stroke, off-label use in TIA). Modified-release dipyridamole 200 mg twice daily may be used if both clopidogrel and aspirin are contraindicated or cannot be tolerated. Aspirin 75mg daily may be used if both clopidogrel and modified-release dipyridamole are contraindicated or cannot be tolerated. Aspirin 75 mg daily with modified-release dipyridamole 200 mg twice daily may be used if clopidogrel cannot be tolerated. Dual therapy with aspirin and clopidogrel may be initiated in secondary care for the first three months following ischaemic stroke or TIA due to severe symptomatic intracranial stenosis or for another condition such as acute coronary syndrome. If the patient is deemed to have a high risk of developing a stroke, patients will have specialist assessment within 24 hours or within 1 week if they are considered low risk. Patients should also be referred to ascertain if carotid endarterectomy surgery is appropriate. Treatment of a Suspected TIA NICE states the following with regards to the treatment of people who have had a TIA within the last week: • Offer aspirin 300 mg immediately unless contraindicated — give a proton-pump inhibitor to anyone with dyspepsia associated with aspirin use. o If aspirin is contraindicated discuss management urgently with the specialist team. o Advise people already taking low dose aspirin regularly to continue — do not offer them aspirin 300 mg. 62 6PY011 TBL: Cardiovascular System Haemorrhagic Stoke Treatment Haemorrhagic strokes are usually treated medically, although some will require neurosurgical intervention. This is not available at all general hospitals and may require patient transfer. All patients with haemorrhagic stroke should have their medications reviewed for any that increase bleeding risk. Oral anticoagulant therapy must be withheld, usually for at least 10-14 days. Re-initiation will depend of the risks of thromboembolic occlusion versus haemorrhagic stroke recurrence. For patients taking vitamin K antagonists such as warfarin, their INR will be normalised usually using a combination of prothrombin complex concentrate and a small intravenous dose (1mg) of vitamin K. For patients taking the newer oral anticoagulant drugs, rivaroxaban, dabigatran or apixaban, INR cannot be used to measure anticoagulation in the patient and vitamin K will not have an anticoagulation reversal effect. Prothrombin complex concentrate can be considered, although there is no robust evidence of its efficacy. This would be used alongside blood tranfusions and intravenous tranexamic acid. On December 17th 2015, idarucizumab (brand name Praxbind) was launched in the UK for the reversal of anticoagulation with dabigatran in patients with life threatening or uncontrolled haemorrhage. It is a humanised monoclonal antibody fragment that has a highly specific binding affinity with dabigatran, therefore reversing the anticoagulant activity of it and its metabolites. There is one specific reversal agent for rivaroxaban or apixaban available, although one called andexanet alfa which was approved for use in 2022. Statins are not routinely recommended in the acute phase following a haemorrhagic stroke as they are associated with an increased risk of haemorrhage. Patients who have suffered a subarachnoid haemorrhage (SAH) will usually be transferred to a neurology unit where available. One of the main complications of a SAH is secondary cerebral ischaemia, which can cause death in those patients who survive the initial bleed. This can be cause by cerebral vasospasm, which can be treated with the calcium channel nimodipine. Nimodipine has selectivity for cerebral vasculature. Patients suffering with a SAH can also be given nimodipine prophylactically to try and prevent cerebral vasospasm. Treatment for all Stroke Patients There has been considerable interest in the use of acute scalp cooling in an attempt to slow brain tissue death and gain additional time to intervene before the damage is irreversible. This followed encouraging results in animal studies. To date, the results in human studies are less convincing, but studies are continuing, and this may possibly form part of treatment in the near future. See: Harris B, Andrews PJD, Murray GD, Forbes J, Moseley O. Systematic review of head cooling in adults after traumatic brain injury and stroke. Health Technol Assess 2012;16:(45). Available at: https://www.ncbi.nlm.nih.gov/books/NBK127507/pdf/Bookshelf_NBK127507.pdf 63 6PY011 TBL: Cardiovascular System Emergency Resuscitation Many patients affected by the conditions discussed here, regularly visit pharmacies and inevitably some with experience an acute event whilst in the pharmacy or in the street outside. NOTE: this is general advice and should not and does not replace professional training! Cardiac arrest is a medical emergency that can strike without warning, including in your pharmacy. CPR (cardiopulmonary resuscitation) is an emergency procedure that is used to restore blood flow to someone who is having cardiac arrest. Without proper blood flow, the brain and organs can be seriously damaged and the person can die within minutes if not treated immediately. By performing simple procedures and following certain guidelines, it may be possible to save lives by giving basic treatment until professional medical help arrives. In an emergency there's no time to read instructions; if you've memorised some of the basic procedures, it will help you react quickly and efficiently. Hands-only CPR To carry out a chest compression: 1. Place the heel of your hand on the breastbone at the centre of the person’s chest. Place your other hand on top of your first hand and interlock your fingers. 2. Position yourself with your shoulders above your hands. 3. Using your body weight (not just your arms), press straight down by 5-6cm (2-2.5 inches) on their chest. 4. Keeping your hands on their chest, release the compression and allow the chest to return to its original position. 5. Repeat these compressions at a rate of 100 to 120 times per minute until an ambulance arrives or you become exhausted. When you call for an ambulance, telephone systems now exist that can give basic life-saving instructions, including advice about CPR. These are now common and are easily accessible with mobile phones. CPR with rescue breaths If you’ve been trained in CPR, including rescue breaths, and feel confident using your skills, you should give chest compressions with rescue breaths. If you're not completely confident, attempt hands-only CPR instead. Adults 1. Place the heel of your hand on the centre of the person's chest, then place the other hand on top and press down by 5-6cm (2-2.5 inches) at a steady rate of 100 to 120 compressions per minute. 2. After every 30 chest compressions, give two rescue breaths. 3. Tilt the casualty's head gently and lift the chin up with two fingers. Pinch the person’s nose. Seal your mouth over their mouth and blow steadily and firmly into their mouth for about one second. Check that their chest rises. Give two rescue breaths. 4. Continue with cycles of 30 chest compressions and two rescue breaths until they begin to recover or emergency help arrives. Video for CPR in adults: https://www.youtube.com/watch?v=BQNNOh8c8ks 64 6PY011 TBL: Cardiovascular System Children over one year old 1. Open the child's airway by placing one hand on the child’s forehead and gently tilting their head back and lifting the chin. Remove any visible obstructions from the mouth and nose. 2. Pinch their nose. Seal your mouth over their mouth and blow steadily and firmly into their mouth, checking that their chest rises. Give five initial rescue breaths. 3. Place the heel of one hand on the centre of their chest and push down by 5cm (about two inches), which is approximately one-third of the chest diameter. The quality (depth) of chest compressions is very important. Use two hands if you can't achieve a depth of 5cm using one hand. 4. After every 30 chest compressions at a rate of 100 to 120 per minute, give two breaths. 5. Continue with cycles of 30 chest compressions and two rescue breaths until they begin to recover or emergency help arrives. Infants under one year old 1. Open the infant's airway by placing one hand on their forehead and gently tilting the head back and lifting the chin. Remove any visible obstructions from the mouth and nose. 2. Place your mouth over the mouth and nose of the infant and blow steadily and firmly into their mouth, checking that their chest rises. Give five initial rescue breaths. 3. Place two fingers in the middle of the chest and push down by 4cm (about 1.5 inches), which is approximately one-third of the chest diameter. The quality (depth) of chest compressions is very important. Use the heel of one hand if you can't achieve a depth of 4cm using the tips of two fingers. 4. After 30 chest compressions at a rate of 100 to 120 per minute, give two rescue breaths. 5. Continue with cycles of 30 chest compressions and two rescue breaths until they begin to recover or emergency help arrives. This video from St John’s Ambulance is a useful reminder of the basics. It is a very good idea for all health professionals to maintain a current first aid certificate and undertake a regular Cardiopulmonary Resuscitation refresher. In many other countries, this is a mandatory requirement to practice. CPR in Children: https://www.youtube.com/watch?v=0aV9NS0ogiM 65