Louie Ischemic Heart Disease

West Coast University, School of Pharmacy Spring 2024 1. arterydisease 2. Coronary 3. 4. 5. Jessica Louie, PharmD, APh, BCCCP Associate Professor, Pharmacy Practice West Coast University, School of Pharmacy Spring 2024 6. 1 DiPiro et al. (2023) Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw-Hill. Chapter 33 Recommended: ¡ Virani SS, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline. Circulation. 2023; 148:e9-e119. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001168 3 Jessica Louie, PharmD, APh, BCCCP 2 Recommended: ¡ To better understand the normal physiology of the heart and the pathophysiology of coronary artery disease (CAD) please watch the following videos: Required: § Understand and know the consequences of myocardial ischemia Be able to describe manifestations of myocardial ischemia and factors that alter the balance between oxygen supply and demand (determinants of myocardial oxygen supply and demand) Be able to differentiate between unstable angina, NonST elevation MI, and ST elevation MI Be able to differentiate between acute coronary syndrome and chronic stable angina Know and understand the therapeutic outcomes desired in patients with underlying coronary artery disease Devise a pharmacologic and monitoring plan for a patient with ischemic heart disease ¡ Pathophysiology of CAD—What is Coronary Artery Disease? Khan Academy: https://tinyurl.com/y3cjyb8v (Duration: 13:38 minutes) ¡ Myocardial oxygen supply—University of British Columbia, UBC Anesthesiology: https://tinyurl.com/yxjouoh3 (Duration: 4:59 minutes) ¡ Myocardial oxygen demand—University of British Columbia, UBC Anesthesiology: https://tinyurl.com/y5488brm (Duration: 4:37 minutes) 4 1 West Coast University, School of Pharmacy ¡ ¡ IHD Medications Patient Cases Spring 2024 ¡ Treatment options Guideline-directed medical therapy (GDMT) ¡ Patient cases throughout presentation ¡ Ischemic Heart Disease Ischemic heart disease background Classification of chest pain and initial assessments ATHEROSCLEROSIS STABLE CORONARY DISEASE ACUTE CORONARY SYNDROMES UNSTABLE ANGINA (UA) CHRONIC STABLE ANGINA (CSA) NON-ST ELEVATION MI (NSTEMI) ST ELEVATION MI (STEMI) 5 Fgs ¡ Coronary blood flow § Vessel patency it § Vascular resistance of coronary arteries § Heart rate ▪ Coronary arteries are perfused during diastole 7 Jessica Louie, PharmD, APh, BCCCP ¡ O2 carrying capacity ¡ Collaterals § Development of new blood vessels (chronic process) É 8 2 West Coast University, School of Pharmacy Spring 2024 ISCHEMIA “Not enough oxygen!” Fyi ¡ ¡ Ischemia → Supply ≠ Demand Myocardial Oxygen Demand (MVO2) § Heart rate strong § Contractility § Wall tension/Wall Stress ▪ Preload ▪ Afterload DEMAND SUPPLY Coronary blood flow Heart rate (Patency, arterial Contractility resistance, diastolic time) Systolic wall tension O2 carrying capacity Collaterals SBP x HR = rate-pressure product (Surrogate for estimating MVO2) Preload Afterload 9 Background Fyi Most common cause of ischemia is diminished coronary artery blood flow. informatio Acute! Therefore, what is/are the most common cause(s) of diminished coronary artery blood flow? Atherosclerotic plaque formation Plaque rupture & atherothrombosis Coronary artery vasospasm* Vasospasm can also occur in the absence of significant atherosclerotic plaques Jessica Louie, PharmD, APh, BCCCP CSA Stable Disease UA AMI Acute Coronary Syndrome 3 West Coast University, School of Pharmacy Spring 2024 jiffy o ATHEROSCLEROSIS (Coronary Artery Disease) Stable Disease Plaque progression and diminishing coronary artery patency How do we determine if chest pain is caused by cardiac ischemia? Stable/Predictable Ischemic Symptoms CHRONIC STABLE ANGINA Plaque instability, plaque rupture, (vasospasm)… How do we determine what is stable and what is unstable? Unstable Disease Acute Symptoms …Partial occlusion of coronary artery UNSTABLE ANGINA …Complete occlusion of coronary artery MYOCARDIAL INFARCTION 14 Chest pain differential 1. Is this pain due to ischemia or not? a. Acuity of the ischemia determine urgency and risk of further myocardial damage. Electrocardiograph (EKG) 2. Are there changes suggestive of acute ischemia or infarction? a. Cardio biomarkers 3. chest tombloodsompies Normally, you only havepain access to 2 criteria immediately (CP, history, EKG) and thus the initial treatment approach is determined from these 2 criteria with a final diagnosis dependent on the 3rd (biomarkers) A Are markers of cardiac damage elevated? a. a. b. Creatine kinase (CK-MD fraction) Troponin I or T Not routine but possibly important 4. a. b. c. so Chest x-ray Echocardiography CT/MRI 15 Jessica Louie, PharmD, APh, BCCCP 16 4 West Coast University, School of Pharmacy Spring 2024 Spectrum of IHD Syndromes Is the chest pain caused by cardiac ischemia? Pff Is the patient experiencing stable angina or an acute coronary syndrome (ACS)? I If ACS, is the syndrome STE or non-STE ACS? s Stable Unstable NSTEMI Angina Angina Chest pain +/+/+/Acute EKG +/-ST↓ +/-ST↓ changes +/-TwI +/-TwI Biomarkers + STEMI +/ST↑ + TwI: T-wave inversion ST: ST segment 17 18 Fya ¡ a u ¡ ¡ Description of pain § Quality ▪ Pressure-like, “elephant sitting on chest”, squeezing, griplike, suffocating, heavy ▪ Not always described as “pain” but commonly as “discomfort” ▪ Almost never sharp or stabbing ▪ Usually does not change with position or respiration ▪ Not reproducible § Location – substernal § Radiation – chest, jaw, shoulder, back, arm § Duration – 30 seconds to 30 minutes Aggravating factors Relieving factors Jessica Louie, PharmD, APh, BCCCP 19 20 5 West Coast University, School of Pharmacy Spring 2024 notintheexam Type Description 1. Substernal chest discomfort with characteristic quality and duration that is 2. Provoked by exertion or emotional stress and 3. Relieved by rest or nitroglycerin (NTG) 1. Ischemic chest pain or not? 1. Stable or Unstable? Atypical angina (probable) Meets 2 of the above characteristics 1. If unstable, is patient high-risk or not? Non-cardiac chest pain Meets 1 or none of the typical anginal characteristics Typical angina (definite) 816 gW z s je É *Women, elderly and patients with diabetes more likely to experience atypical angina 21 Histone SU is a 52 y/o HM smoker (30 pack year) with HTN, DM who reports experiencing “pressure” in the central chest with radiation into both arms. The pain worsens by physical exertion and is relieved promptly by rest. This symptom has been present for approximately 1 year. It is non-progressive in nature and does not alter his lifestyle to any significant degree. chronic Is SU experiencing CSA or UA? unstable 23 Jessica Louie, PharmD, APh, BCCCP 22 CP is a 55 y/o AAF with PMH of CAD, DM, dyslipidemia, HTN complaining of intense pressure-like pain, 7/10, in the substernal area radiating to left arm, neck and jaw which started when she lifted the heavy water bottle to replace the empty one in the water cooler. It went away after 1 tablet of NTG. Over the past 24 hours she had 3-4 episodes of chest pain lasting 10-20 minutes per episode. The pain progressively worsened and now she describes the intensity to be 10/10 even after 3 tablets of NTG. Her BP is stable. An EKG is obtained which reveals no acute changes. 24 6 West Coast University, School of Pharmacy Spring 2024 What type of chest pain is CP experiencing? ¡ Typical, atypical or non-ischemic? ¡ If it is cardiac, is it stable or unstable? ¡ Further diagnostic testing is based on exercise capacity of patient: ¡ Intermediate risk: ice nonincas § Standard exercise EKG testing ¡ Intermediate to high risk: § Exercise stress or pharmacological stress with nuclear MPI or EKG (Class Ib) 25 26 8kill ¡ ¡ at g Fyi IHD is a chronic disorder Disease typically cycles through defined phases (not necessarily in linear order): ¡ Of § Socio-demographic characteristics ▪ Age is single strongest determinant of survival § Cardiovascular risk factors § Asymptomatic § Stable angina ▪ Smoking, HTN, dyslipidemia, family history of premature CAD, obesity, sedentary lifestyle § Accelerating angina s § Coexisting medical conditions § ACS (UA or AMI) ▪ DM, CKD, COPD, malignancy how § Cardiovascular comorbidities acute syndrome cornony ▪ Heart failure, PAD 27 Jessica Louie, PharmD, APh, BCCCP i Prognosis of IHD for Death or Nonfatal MI: 28 7 West Coast University, School of Pharmacy Spring 2024 Fyi Fyi ¡ Prognosis of IHD for Death or Nonfatal MI: ¡ § Psychosocial characteristics T-wave inversion § May represent myocardial ischemia ▪ Depression § Health status ▪ Patients’ symptoms, functional capacity, quality of life ¡ § Anginal frequency ST segment depression § May represent myocardial ischemia ▪ Frequency of angina § More sensitive than T wave inversion § Cardiac disease severity ▪ Degree and distribution of stenoses measured by coronary angiography 29 30 Fyn ¡ ¡ ST segment elevation § Diagnostic for acute infarction § Must be ≥1 mm in 2 contiguous leads § Reversible Q wave § Indicates transmural infarct § Can be old or new, therefore not diagnostic for acute infarct § Irreversible Jessica Louie, PharmD, APh, BCCCP 31 ¡ Creatine phosphokinase – muscle brain (CK-MB) isoenzyme ¡ Troponin I or Troponin T (most specific) 32 8 West Coast University, School of Pharmacy Spring 2024 important ¡ important I 2 Creatine phosphokinase – muscle brain (CK-MB) isoenzyme ¡ Troponin I or Troponin T (most specific) knowifit's § CK-MB is only isoform in myocardial tissue § Rise in CK is proportional to amount of damage heartattack new § CK-MB fraction >5% (with elevation in total CK) is diagnostic for MI at 8-12 hours ores MBizschigh neediocookatfaction CFB § Rise in Tropoinin I or T is proportional to amount of damage § Elevation may persist for 5-7 days (longer in renal example canso § Regulatory protein with high specificity for cardiac tissue § Peak sensitivity at 8-12 hours § Elevation usually dissipates within 48-72 hours Normal Value CK 0-150 U/L CK-MB 0-12 U/L § Current standard to rule in or out an AMI 33 insufficiency) Troponin I or T level <0.01 0.01-0.12 >0.12 Interpretation Normal (check local lab) Troponin “leak” Positive for MI so.is 016100 16.61 si diagnostic aseitherneedto retestor 34 needckMB come formsat Erhr Time Course of Biomarkers mgdemageitis fisherthecate Guideline-Directed Medical Therapy (GDMT) 35 Jessica Louie, PharmD, APh, BCCCP 36 9 West Coast University, School of Pharmacy + Anti-platelet Spring 2024 + Anti-anginal Disease Modifying 37 ¡ Anti-platelet § § Prasugrel ¡ Disease-modifying = or atherosclerosis modifying of § ACE-inhibitors thinking Clopidogrel naredning § Aspirin arteries § Ticagrelor 38 ¡ § ARBs § Statins Prevent MI and death à increase “quantity” of life § Highest priority § Anti-platelet and disease modifying therapy 2¡ Reduce symptoms of angina and occurrence of § Ticlopidine ischemia à improve quality of life § Greater concern from patient’s perspective § Anti-anginals ¡ Anti-anginal = Anti-ischemic § Beta blockers § Calcium channel blockers § Nitrates 39 Jessica Louie, PharmD, APh, BCCCP 40 10 West Coast University, School of Pharmacy ¡ Spring 2024 Aspirin § 75-162 mg daily continued indefinitely in absence of contraindications in patients with SIHD § Example: Aspirin 81 mg po daily ¡ First line: nonpharmacologic strategies § Nonpharmacologic strategies are recommended as first- line therapy to lower BP in those with elevated BP (120129/<80 mm Hg) ¡ IHD with diagnosed hypertension, a BP target of ¡ <130/<80 mm Hg is recommended to reduce CVD events and all-cause death Clopidogrel § Treatment reasonable when aspirin is contraindicated jpg Circulation. 2012;126:e354-e471. 41 42 ¡ ¡ Guideline directed medical therapy first line therapy: § angiotensin-converting enzyme (ACE) inhibitor § angiotensin-receptor blockers (ARB) § beta blockers id Lo PII Long-term beta-blocker therapy is not recommended to improve outcomes in patients with IHD in the absence of myocardial infarction in the past year, left ventricular ejection fraction ≤50%, or another primary indication for beta-blocker therapy Etf sarton ¡ Additional antihypertensive medications as needed to optimize BP control § Dihydropyridine calcium channel blockers (CCB) § long-acting thiazide diuretics ¡ Beta-Blocker – first line therapy ¡ Calcium channel blocker – first line therapy § DOC (drug of choice) for Prinzmetal angina § Short acting dihydropyridine CCB should NOT be used § mineralocorticoid receptor antagonists 43 Jessica Louie, PharmD, APh, BCCCP 44 11 West Coast University, School of Pharmacy ¡ Spring 2024 Nitrates ¡ § Long-acting nitrates (with or w/o CCB) as a substitute for BB if ACE/ARB § ACE-inhibitor in all patients with SIHD who also have: unable to use BB for relief of symptoms (unless contraindicated) § Long-acting nitrates (with or w/o CCB) + BB if treatment ▪ ▪ ▪ ▪ unsuccessful with BB alone § Sublingual nitroglycerin or nitroglycerin spray for immediate relief of angina in patients with SIHD Hypertension Diabetes mellitus LVEF 40% or less CKD § ARBs may be substituted for ACE-inhibitors when patients are intolerant to ACE-inhibitors 45 ¡ 46 Statins ¡ § Moderate or high dose statin therapy § High-Dose Statin Therapy: ▪ Atorvastatin 80 mg po daily or 40 mg po daily ▪ Rosuvastatin 40 mg po daily or 20 mg po daily § Therapy with rosiglitazone should not be initiated in patients with SIHD § See additional diabetes management in Endocrine § Reduced intake of saturated fats (to <7% of total calories), course trans fatty acids (to <1% of total calories) and cholesterol (to <200 mg/day) 47 Jessica Louie, PharmD, APh, BCCCP Diabetes management 48 12 West Coast University, School of Pharmacy ¡ ¡ Spring 2024 Evaluate every 1-2 months until goals achieved Goals include: ¡ Patient education § Individual education plans to optimize care and § BP goal § Use of high-intensity statin, monitoring and tolerance promote wellness § A1c achieved § Smoking cessation discussed and/or started ¡ ¡ ¡ ¡ ¡ ¡ § Healthy weight ¡ Symptom Assessment § Number of angina episodes per week § Number of Nitroglycerin SL tabs taken per week § Exercise capacity § Engagement in activities they enjoy doing ¡ Questionnaires available ▪ Motivational interviewing Physical activity Heart healthy diet rich in fruits & vegetables Reduced dietary sodium Reduction or elimination of alcohol intake Smoking cessation counseling Management of psychological factors § Seattle Angina Questionnaire § CCS Angina Grading Scale 49 § DiPiro et al. (2023) Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw-Hill. Chapter 33 § Virani SS, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline. Circulation. 2023; 148:e9-e119. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001168 ¡ Fihn SD, Blankenship JC et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease. JACC. 2014;64:1929-1949. http://content.onlinejacc.org/article.aspx?articleid=1891717 ¡ Fihn SD, Gardin JM et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease. Circulation. 2012;126:354-471. http://circ.ahajournals.org/content/126/25/e354 Thank you for your attention ANY QUESTIONS??? 51 Jessica Louie, PharmD, APh, BCCCP 50 Jessica Louie, PharmD, APh, BCCCP jLouie@westcoastuniversity.edu 52 13