Acute Coronary Syndromes

West Coast University, School of Pharmacy Spring 2024 ¡ ¡ ¡ ¡ ¡ Jessica Louie, PharmD, APh, BCCCP Associate Professor, Pharmacy Practice West Coast University, School of Pharmacy Spring 2024 1 Required: § DiPiro et al. (2023) Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw-Hill. Chapter 34 Recommended: ¡ 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation. 2021;144:e368–e454. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001029 2 ¡ ¡ ¡ ¡ ¡ Amsterdam EA, Wenger NK et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST Elevation Acute Coronary Syndromes: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:344-426. http://circ.ahajournals.org/content/130/25/e344.full.pdf+html ¡ O’Gara PT, Kushner FG, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. JACC. 2013;61:78-140. http://content.onlinejacc.org/article.aspx?articleid=1486115 ¡ 3 Jessica Louie, PharmD, APh, BCCCP Classify ACS as UA, NSTEMI, or STEMI Stratify ACS patients based on risk category Create an acute pharmacologic management plan for an ACS patient Identify the indications and contraindications for thrombolytic therapy Create a long-term post-ACS pharmacologic management plan for a patient Pathophysiology Diagnosis/Risk stratification Medications for ACS Acute Management Long-Term Management 4 1 West Coast University, School of Pharmacy Spring 2024 Myocardial Oxygen Supply/Demand Mismatch Supply 1. 2. 3. 4. Demand 5. Coronary blood flow O2 saturation Diastolic filling time Heart Rate Contractility Wall Tension – Preload, Afterload Atherosclerotic plaque formation Plaque rupture Platelet recruitment Thrombus formation Supply Acute occlusion 1. Decreased oxygen supply Demand 2. Ischemia 3. Acute infarction http://angercoach.com/blog/?p=422 http://www.medicalscale1.com/tag/best-weight-scale/ 5 ¡ ¡ ¡ ¡ ¡ 6 12-lead EKG within 10 minutes of arrival Serial EKG every 15-30 minutes during first hour in symptomatic patients Measure cardiac troponin in all patients Measure serial cardiac troponin I or T every 36 hours Use risk stratification models for management 7 Jessica Louie, PharmD, APh, BCCCP 2 West Coast University, School of Pharmacy Spring 2024 Angina Stable Unstable NSTEMI Angina Angina Chest pain +/- Acute EKG changes - Biomarkers - STEMI ST Elevation? +/- +/- +/- Yes +/-ST↓ +/-TwI +/-ST↓ +/-TwI ST↑ STEMI - + + NSTEMI 11 Jessica Louie, PharmD, APh, BCCCP No Biomarkers ? Positive Negative UA 12 3 West Coast University, School of Pharmacy Spring 2024 ¡ Admission vs. Observation ¡ All STEMI patients are high risk ¡ Anticoagulant/Antithrombotic use ¡ Immediate reperfusion necessary ¡ Invasive vs. Medical management ¡ Risk assessment tool exists but does not alter acute patient management 13 ¡ TIMI risk score for NSTE-ACS § TIMI = Thrombolysis in Myocardial Infarction § 1 point is assigned for each of 7 medical history and clinical 14 ¡ Affects prognosis and urgency of catheterization ¡ TIMI risk score for NSTE-ACS presentation findings Age 65 years or older 3 or more CHD risk factors: smoking, hypercholesterolemia, HTN, DM, family hx of premature CHD deaths/events 3. Known CAD 4. Aspirin use within last 7 days 5. 2 or more episodes of chest discomfort within last 24 hours 6. ST-segment depression 0.5 mm or greater 7. Positive biochemical marker for infarction 1. 2. 15 Jessica Louie, PharmD, APh, BCCCP High risk Medium risk Low risk 5-7 points 3-4 points 0-2 points 16 4 West Coast University, School of Pharmacy MI Type STEMI Goals of Reperfusion therapy as soon as Care possible • Primary PCI preferred if it can be performed within 90 min of medical contact • If primary PCI is unavailable within 90 min of medical contact, thrombolytics within 30 min of presentation unless contraindications exist • If primary PCI is not available, transfer to a capable hospital and give within 120 minutes of medical contact Spring 2024 N-STEMI Prevent total occlusion of the vessel • Decision and need for revascularization (PCI or surgery) vs. medical management should be made on basis of risk stratification, symptom resolution, and indicators of ongoing myocardial damage/ischemia ¡ ¡ ¡ ¡ ¡ Acute Supportive Care (THROMBINS2) Antiplatelets Anticoagulant Revascularization (PCI/CABG/Thrombolytics) Anti-anginal therapies 17 THROMBIN2 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ (MONA no longer used) ¡ Thienopyridine (P2Y12 inhibitor) Heparin Renin-angiotension-aldosterone system Oxygen Morphine Beta-blocker Intervention (PCI) Nitroglycerin Statin/Salicylate (aspirin) Inhibit platelet activation Four aspirin 81 mg each (324 mg total ) OR ¡ One 325 mg tablet (non-enteric coated) CHEWED and SWALLOWED immediately ¡ 19 Jessica Louie, PharmD, APh, BCCCP 18 20 5 West Coast University, School of Pharmacy ¡ Preferred agent for ischemia-related pain ¡ Sublingual NTG Spring 2024 ¡ § SBP <90 mmHg § Patient received oral PDE5 inhibitor within past 24-48 § 0.4mg SL every 5 minutes x3 hours § Take 1 SL tablet at first sign of chest pain. Wait 5 minutes. ▪ ▪ ▪ ▪ If pain persists, take a 2nd SL tablet while you call 911. While waiting for ambulance, can take a 3rd SL tablet if chest pain persists after 5 minutes. ¡ Caution use if: Nitroglycerin drip § 5-10mcg/min IV, increase by 10mcg/min every 3-5 min ¡ until ischemia resolved § Tachyphylaxis within 24-48hr Avanafil: within 12 hours Sildenafil: within 24 hours Vardenafil: within 24 hours Tadalafil: within 48 hours Monitoring § HR, BP, HA 21 ¡ ¡ 2-4 L/min oxygen through nasal cannula Administer if O2 saturation < 90% 22 ¡ Refractory pain ¡ 2-4mg IV every 5-15min PRN pain ¡ Relieve pain because pain can worsen ischemia § Pain à stress response à epinephrine release & tachycardia § Decreases myocardial oxygen demand ¡ Monitoring § Respiratory Rate, Heart Rate, Blood pressure 23 Jessica Louie, PharmD, APh, BCCCP 24 6 West Coast University, School of Pharmacy Spring 2024 ¡ Alternative analgesics may be favored over morphine now due to clinical trial data associating it with risk of death… ¡ Fentanyl ¡ § Less histamine release § Less hypotensive effect ¡ 25-100 mcg IV Q5-15 min PRN pain ¡ Monitoring ¡ ¡ § RR, HR, BP N Engl J Med 2014;371:1016-27 Am Heart J 2005;149:1043-9 MW, a 58yo WM, with ____ (hint: negative troponin and ST depression on EKG) was started on a NTG drip and the dose was titrated to 15mcg/min, at which point the patient was chest pain free and his BP was 134/72. The next day, the patient is complaining of chest pain. His blood pressure is 148/88. What is the likely cause of the recurrence of chest pain in this patient? 25 ¡ ¡ ¡ ¡ ¡ Acute Supportive Care Antiplatelet Anticoagulant Target pathophysiology Thrombolytic (Go after occlusion) Anti-ischemic 26 X Fondaparinux Prasugrel Ticagrelor Ticlopidine X X X X X X Selwyn AP. Am J Cardiol 2003;91:3H-11H. 27 Jessica Louie, PharmD, APh, BCCCP 28 7 West Coast University, School of Pharmacy Spring 2024 ¡ ¡ ¡ Aspirin P2Y12 Inhibitors GP IIb/IIIa Inhibitors 29 30 ¡ ¡ Four aspirin 81 mg each (324 mg total ) OR ¡ One 325 mg tablet (non-enteric coated) CHEWED and SWALLOWED immediately ¡ ¡ ¡ Clopidogrel (Plavix®) Prasugrel (Effient®) Ticagrelor (Brilinta®) Cangrelor (Kengreal®) Maintenance dose: 81 mg po daily ¡ Monitoring § Platelets, H/H, bleeding 31 Jessica Louie, PharmD, APh, BCCCP 32 8 West Coast University, School of Pharmacy ¡ ¡ Spring 2024 Irreversible inhibitor (DRUG half-life doesn’t matter) Dose ¡ ¡ § 300 mg PO x1 (600 mg PO x1 if <6 hours until catheterization) § Followed by 75 mg PO daily ¡ § Poor metabolizers? § PPI interaction? – omeprazole? Prodrug § 2 step activation to active metabolite § CYP oxidation ▪ Primarily CYP2C19 ¡ 1 High interpatient variability in response Decreased platelet inhibition = increased thrombosis risk 2 Management § Increase bolus/maintenance dose? § Test for CYP2C19 genotype? § Choose different P2Y12 inhibitor? 33 ¡ 34 § Irreversible inhibitor Caution/Contraindication § Active bleeding § Concomitant use of strong CYP2C19 inhibitor ¡ § Black Box Warning ¡ ¡ ▪ Dose of 5 mg daily considered if patient <60 kg Monitoring § CBC, bleeding 1 35 Jessica Louie, PharmD, APh, BCCCP ▪ DRUG half-life doesn’t matter Prodrug ▪ 1 step CYP oxidation to active metabolite 60mg PO x1 then 10mg PO daily 36 9 West Coast University, School of Pharmacy ¡ Spring 2024 • Reversible inhibitor Caution/Contraindication ▪ DRUG half-life does matter § Active bleeding (Black Box Warning) § Age > 75 § Prior TIA/CVA (Black Box Warning) ¡ 180mg PO x1 then 90mg PO BID § Weight < 60kg ¡ ¡ Not a prodrug Monitoring § CBC, bleeding 37 ¡ 38 • ATP analogue Caution/Contraindication ▪ ASA dose > 100mg (Black Box Warning) ▪ Moderate to severe hepatic dysfunction • Reversible binding IV medication: 30 mcg/kg IV bolus followed by 4 mcg/kg/min IV infusion for at least 2 hours or duration of PCI ¡ ¡ Monitoring § Platelets, H/H, bleeding ¡ 39 Jessica Louie, PharmD, APh, BCCCP Platelet recovery after cessation of therapy: 1-2 hours 40 10 West Coast University, School of Pharmacy Prodrug Clopidogrel Prasugrel Yes (2 steps) Yes (1 step) No No 2C19 3A4, 2B6 None None Irreversible Irreversible Reversible Reversible 2 hours 30 min 60 min 2 min Daily Daily BID IV Medical or PCI PCI Medical or PCI PCI Moderate to strong 2C19 inhibitor use Hx CVA/TIA, < 60kg, > 75y.o. Concomitant ASA > 100mg N/A 5 days 7 days Activation Enzyme P2Y12 binding Onset Dosing Frequency Patients Caution/ Contraindicated Spring 2024 Ticagrelor Cangrelor ¡ ¡ LD = loading dose Time to CABG ¡ ¡ ¡ ¡ ¡ 3 days 2 hours Reversible inhibitor • Tirofiban – Aggrastat® • Eptifibatide – Integrilin® • Abciximab – ReoPro® Inhibit GPIIb/IIIa-fibrinogen binding à inhibit platelet aggregation IV infusions 42 ¡ Caution/Contraindications § Active bleeding § CVA in last 30 days Dose § History of hemorrhagic CVA § Severe hypertension Duration ¡ § 12-24 hours Monitoring § Platelets, H/H, BUN, SCr, bleeding 43 Jessica Louie, PharmD, APh, BCCCP TEA – AIR for generic/brand names of Glycoprotein IIb/IIIa inhibitors 41 § 25 mcg/kg over 5 minutes, then 0.15 mcg/kg/min § Renal dose reduction for CrCl <30 mL/min ¡ Tirofiban (Aggrastat®) Eptifibatide (Integrilin®) Abciximab (ReoPro®) – discontinued 44 11 West Coast University, School of Pharmacy ¡ Reversible inhibitor ¡ Dose Spring 2024 ¡ § Active bleeding § CVA in last 30 days § 180mcg/kg (max 22.6mg) IV x1 then 2mcg/kg/min § History of hemorrhagic CVA § Severe hypertension § Hemodialysis (max 15mg/hr) § Renal dose adjustment for CrCl <50 mL/min ¡ Caution/Contraindications Duration ¡ § Medical management: 72hr or until discharge § PCI: 18-24hr Monitoring § Platelets, H/H, BUN, SCr, bleeding 45 Tirofiban (Aggrastat®) Eptifibatide (Integrilin®) Abciximab (ReoPro®) Inhibition Competitive Competitive Non-competitive Irreversible? No No Yes Yes, CrCl <50 mL/min and avoid in dialysis No CVA 30 days CVA 30 days CVA 2 years PCI & medical PCI & medical PCI only (within 12 hours) Renal adjustment Yes, CrCl <30 mL/min Caution/ Contraindicated Indication ¡ NSTE-ACS = UA or NSTEMI § All patient receive at least 2 antiplatelet therapies ▪ ASA + clopidogrel/ticagrelor *Ticagrelor is preferred § Patients with high risk features receive triple therapy ▪ ASA + P2Y12 inhibitor + GP IIb/IIIa inhibitor 47 Jessica Louie, PharmD, APh, BCCCP 46 48 12 West Coast University, School of Pharmacy ¡ Spring 2024 A 56 yo male is taken to the cath lab after being brought in to the ED with high-risk NSTEMI. The MD tells you he thinks the patient will probably require CABG and the CT surgeons are ready to operate in the next 24 hours if necessary. The MD wants to know what antiplatelet agent(s) to avoid. STEMI § All patients receive dual antiplatelet therapy ▪ Fibrinolytic: ASA + Clopidogrel ▪ PCI: ASA + P2Y12 inhibitor What additional information do you need to make this decision? § Some PCI patients may receive triple antiplatelet What antiplatelet agent(s) would you recommend avoiding in this patient? therapy based on MD preference (e.g. large thrombus burden, inadequate P2Y12 inhibitor loading) ▪ ASA + P2Y12 inhibitor + GP IIb/IIIa inhibitor *Preferred eptifibatide or tirofiban What antiplatelet agent(s) should be administered to this patient? 49 50 ¡ ¡ ¡ ¡ 51 Jessica Louie, PharmD, APh, BCCCP Unfractionated Heparin (UFH) Enoxaparin (Lovenox®) Fondaparinux (Arixtra®) Bivalirudin (Angiomax®) 52 13 West Coast University, School of Pharmacy Spring 2024 • STEMI with fibrinolytics or NSTE-ACS: ¡ • 60 units/kg IV x1 (max 4,000 units) then 12 units/kg/hr (max 1,000 units/hr) • Continue for 48 hours or until PCI performed • Can continue up to 8 days or discharge • STEMI with PCI and with GP IIb/IIIa receptor antagonist planned • 50-70 units/kg IV bolus to achieve therapeutic ACT • Discontinue after PCI • STEMI with PCI and with NO GP IIb/IIIa receptor antagonist planned • 50-00 units/kg IV bolus to achieve therapeutic ACT • Discontinue after PCI Caution/Contraindication § History of heparin-induced thrombocytopenia (HIT) § Active bleeding § Aortic dissection ¡ Monitoring § Platelets, H/H, bleeding, APTT § ACT = activated clotting time ▪ Used to monitor treatment with high dose heparin before, during and shortly after medical procedures 53 Age group < 75 CrCl Bolus Dose Maintenance Dose ≥ 30mL/min 30mg IV x1 1mg/kg SQ Q12 Max Dose first 2 doses 100mg ≥ 75 ≥ 30mL/min None 0.75mg/kg SQ Q12 75mg < 75 < 30mL/min 30mg IV x1 1mg/kg SQ daily None (100mg?) ≥ 75 < 30mL/min None 1mg/kg SQ daily None (100mg?) 54 CrCl Bolus Dose Maintenance Dose Max Dose first 2 doses ≥ 30mL/min None 1mg/kg SQ Q12 None < 30mL/min None 1mg/kg SQ daily None If patient receives PCI: Additional 0.3mg/kg IV x1 if last dose > 8 hours prior 55 Jessica Louie, PharmD, APh, BCCCP 56 14 West Coast University, School of Pharmacy ¡ Spring 2024 • Caution/Contraindication Duration ▪ Active bleeding ▪ CrCl < 30mL/min (monitor anti-Xa?) § STEMI: 8 days or until discharge § NSTE-ACS: until resolution of ischemia (≥ 2 days) ¡ Monitoring ▪ Platelets, H/H, BUN, SCr, bleeding ▪ Anti-Xa (sometimes) 57 UFH Enoxaparin Monitoring aPTT None usually (Anti-Xa in select groups) Reversibility More complete, Easier More difficult Less impact More impact Half-life 1.5 h 4.5-7 h IV administration Drip Boluses Efficacy Lower Higher Bleeding risk Lower STEMI – Higher NSTE-ACS – Higher? Renal Dysfunction 58 ¡ STEMI with fibrinolytic therapy § 2.5 mg IV x1 then 2.5 mg SQ daily starting the following day § Up to 8 days or until discharge or revascularization ¡ STEMI with primary PCI § Not recommended as sole anticoagulant for primary PCI ¡ NSTE ACS § 2.5 mg SQ daily, additional anticoagulant will be needed if PCI is performed 59 Jessica Louie, PharmD, APh, BCCCP 60 15 West Coast University, School of Pharmacy Spring 2024 Patient Population • Contraindications ▪ Active Bleeding ▪ CrCl < 30mL/min ¡ Monitoring ▪ H/H, BUN, SCr, bleeding IV Bolus IV Maintenance NSTE ACS (Medical Management) 0.1mg/kg 0.25mg/kg/hr PCI (already on bivalirudin) PCI (not on bivalirudin) 0.5mg/kg 1.75mg/kg/hr* 0.75mg/kg 1.75mg/kg/hr* *Can reduce infusion to 1 mg/kg/hour with estimated CrCl <30 mL/min 61 ¡ Duration § PCI • Discontinue 0-4 hours after PCI • If additional anticoagulation is needed after 4 hours post-PCI, may continue at 0.2 mg/kg/hour for up to additional 20 hours § NSTE ACS ▪ Continue until diagnostic angiography or PCI ¡ Special populations § Heparin-Induced Thrombocytopenia (HIT) § Anti-thrombin deficiency ¡ Caution/Contraindication § Caution use with GPIIb/IIIa inhibitors – may be concomitantly used if clinically indicated during PCI § Active bleeding ¡ Monitoring § H/H, BUN, SCr, bleeding 63 Jessica Louie, PharmD, APh, BCCCP 62 64 16 West Coast University, School of Pharmacy ¡ Spring 2024 NSTE-ACS and STEMI: ¡ § All patient should receive an anticoagulant in addition to antiplatelet therapies ▪ UFH ▪ Enoxaparin ▪ Fondaparinux ▪ Bivalirudin ¡ ¡ Labs: Na 134, K 5.1, Cl 105, HCO3 19, BUN 41, SCr 5.1, WBC 4.1, H/H 10.1/30.1, Platelets 201, Troponin 0.7 Weight= 75 kg EKG: RRR, T wave inversions in V3-V6 ¡ How would you classify this patient’s ACS? ¡ What anticoagulant would you start for this patient? At what dose? ¡ Jessica Louie, PharmD, APh, BCCCP FH, a 65 yo HF, presents to the ED complaining of substernal chest pressure that feels like something is squeezing her heart. Sitting down did not reduce the pain. This feeling has lasted for 30 minutes and is associated with 6/10 pain. She does not feel any pain anywhere else. She took one of her husband’s SL NTG but the pain did not change. 65 66 67 68 17 West Coast University, School of Pharmacy Spring 2024 ¡ Fibrin-specific: ¡ Alteplase (Activase®) or “tPA” ¡ Reteplase (Retavase®) or ”rPA” ¡ Teneteplase (TNKase®) or “TNK-tPA” STEMI only! § Within 12h of symptom onset § Evidence of ongoing ischemic 12-24 hours after symptom onset and large area of myocardium at risk or hemodynamic instability § Use if rapid PCI not possible (first medical contact to device time at PCI-capable hospital >120 minutes) Non-fibrin specific: ¡ Streptokinase ▪ Door-to-needle = 30min ▪ (Door-to-balloon = 90min) § No longer marketed in the US but is available in other countries 69 Agent Alteplase (tPA)* Reteplase (rPA)* Tenectaplase (TNK)* Streptokinase Dosing 15mg IV over 1-2 min then 0.75mg/kg IV (max 50 mg) over 30min then 0.5mg/kg (max 35 mg) over 1 hour, total dose not to exceed 100 mg 10 units IV over 2 min Then 10 units IV over 2 min, 30 min later Fibrin Selective Plasminogen Binding Duration of Infusion (min) Half-Life (min) Early Heparin 30-50mg IV x1 (weight-based bolus) 1.5 million units IV over 1 hour 71 Streptokinase tPA (Alteplase) No Yes Indirect Direct Reteplase (Retevase) Yes Direct Tenecteplase (TNKase) Yes > tPA Direct 60 90 10 +10 5-10 sec 23 Unknown <5 Yes 13-16 Yes 20 Yes Hypotension Yes No No No Allergic Rxn Yes No No No TIMI Reflow III @ 90 min 32 45-54 60 = tPA 81-88 78-89 Yes n/a Yes n/a Yes (single bolus) @ 24 hrs Given IV bolus *Must be administered with UFH or LMWH Jessica Louie, PharmD, APh, BCCCP 70 72 18 West Coast University, School of Pharmacy ABSOLUTE Spring 2024 Relative Active bleeding Recent (within 2-4 weeks) internal bleeding Known intracranial neoplasm Traumatic or prolonged (>10 min) CPR Any prior intracranial hemorrhage Recent major surgery (<3 weeks) Ischemic stroke within previous 3 months (EXCEPT acute ischemic stroke within 4.5 hours) ¡ Nitroglycerin Ischemic stroke more than 3 months ago ¡ Known cerebral vascular malformation Known intracranial pathology not covered in absolute contraindications (dementia) ¡ Aortic dissection Poorly controlled HTN or BP > 180/110 Beta-blockers Non-dihydropyridine calcium channel blockers (Non-DHP CCB) Closed head or facial trauma within previous 3 months Current oral anticoagulant use Intracranial or intraspinal surgery within 2 months Noncompressible vascular punctures Severe uncontrolled hypertension (unresponsive to emergency therapy) Pregnancy § Already covered in supportive therapies Active peptic ulcer 73 74 Goal: Immediate reperfusion ¡ ¡ Fibrinolytic or PCI Antiplatelet (at least 2) § ASA § P2Y12 inhibitor § +/- GP IIb/IIIa during PCI ¡ Anticoagulant (pick 1) § § § § 75 Jessica Louie, PharmD, APh, BCCCP UFH Enoxaparin Fondaparinux Bivalirudin 76 19 West Coast University, School of Pharmacy Spring 2024 Medium to high risk ¡ ¡ ¡ Fibrinolytics? Antiplatelets? NO! Yes § ASA? Yes § P2Y12 inhibitor? Yes § GP IIb/IIIa inhibitor? Yes Anticoagulants? § § § § UFH? Enoxaparin? Fondaparinux? Bivalirudin? Low risk ¡ ¡ Initial triple antiplatelet with ASA + P2Y12 inhibitor + GP IIb/IIIa inhibitor ¡ Yes (pick 1) Maybe Preferred Maybe Maybe 77 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ABCDE – ASA Post-management in all patients Statin • Antiplatelet / Anticoagulant Beta-blocker • Blood pressure (BB, ACE/ARB, ACE-I/ARB NTG) Aldosterone Inhibitor • Cholesterol and cigarettes (smoking cessation) SL NTG • Diet and DM management • Exercise Smoking cessation DM control Lifestyle modifications NO! Yes § ASA? Yes § P2Y12 inhibitor? Yes § GP IIb/IIIa inhibitor? No Anticoagulants? Yes § § § § Maybe Preferred Maybe No UFH? LMWH? Fondaparinux? Bivalirudin? Intensify regimen if risk level increases 78 Secondary prevention of ischemic events over time.1,2,97 (AA, aldosterone antagonist; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; CI, contraindications; DAPT, dual antiplatelet therapy; DM, diabetes mellitus; HF, heart failure; LDL-C, Low Density Lipoprotein Cholesterol (70 mg/dL is expressed in SI units as 1.81 mmol/L); LVEF, left ventricular ejection fraction (40% is expressed in SI units as a fraction, ie, 0.40); MI, myocardial infarction; NSAID, nonsteroidal anti-inflammatory drug; PCSK9, proprotein convertase subtilisin-kexin type 9; SL NTG, sublingual nitroglycerin.) 79 Jessica Louie, PharmD, APh, BCCCP Fibrinolytics? Antiplatelets? Citation: Chapter 33 Acute Coronary Syndrome, DiPiro JT, Yee GC, Posey L, Haines ST, Nolin TD, Ellingrod V. Pharmacotherapy: A Pathophysiologic Approach, 11e; 2020. Available at: https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577§ionid=226722807 Accessed: January 27, 2021 Copyright © 2021 McGraw-Hill Education. All rights reserved 20 West Coast University, School of Pharmacy ¡ Spring 2024 Decrease in CAD death rates since 1968 ¡ § 47% of reduction attributable to treatments Low-dose (75-162mg/day) – 81 mg po daily § Secondary prevention § ALL PATIENTS (unless contraindicated) ▪ 10% initial treatments for ACS ▪ 11% secondary preventive therapies § 44% of reduction attributable to risk factor § Continue indefinitely reduction ▪ ▪ ▪ ▪ ▪ 24% cholesterol 20% SBP 12% smoking incidence +8% BMI increase +10% diabetes increase 81 ¡ All patients unless contraindications ¡ Early Benefits 82 ¡ All patients unless contraindicated § Symptomatic bradycardia/hypotension § 2nd or 3rd degree heart block § Severe COPD/asthma § Pleiotropic effects, plaque stabilization ¡ ¡ Late Benefits § Reduces myocardial O2 demand/ischemia § Inhibits deleterious effects of NE/remodeling § Secondary prevention § LDL goal < 100mg/dL (or < 70mg/dL)? § Reminder: No simvastatin 80 mg, watch ¡ Decreased myocardial oxygen demand § Negative chronotrope/inotrope interactions 83 Jessica Louie, PharmD, APh, BCCCP Inhibits SNS effects 84 21 West Coast University, School of Pharmacy ¡ Spring 2024 All post-MI patients within 24 hours unless contraindicated ¡ § Symptomatic hypotension § Contraindications: CKD, hyperkalemia § Acute kidney injury § Refractory hyperkalemia ¡ ¡ Patients with left ejection fraction < 40% and either DM or symptoms of heart failure Continue indefinitely ¡ Spironolactone (Aldactone®) ¡ Eplerenone (Inspra®) § 12.5-25mg PO daily Use ACE-I unless intolerable § 25-50mg PO daily § Cough § Angioedema (possibly) 85 ¡ All patients unless contraindications ¡ Relief of anginal pain • Diagnostic § Coronary Angiography § No evidence of therapeutic benefit ¡ ¡ Intervention If no relief, call 911 after 1 dose (not 3) § Percutaneous Intervention (PCI) § 0.4mg SL every 5 minutes x3 § Take 1 SL tablet at first sign of chest pain. Wait 5 minutes. § Percutaneous Transluminal Coronary Angioplasty (PTCA) § Coronary Artery Bypass Graft (CABG) 2nd SL If pain persists, take a tablet while you call 911. While waiting for ambulance, can take a 3rd SL tablet if chest pain persists after 5 minutes. ¡ 86 Important to counsel patients on proper use 87 Jessica Louie, PharmD, APh, BCCCP 88 22 West Coast University, School of Pharmacy ¡ Spring 2024 Identify coronary occlusions ¡ ¡ Successor to PTCA Reopens occluded arteries http://www.ispub.com/journal/the_internet_journal_of_cardiology/volume_2_number_2_9/article_printable/electrocardiogr aphic_diagnosis_of_critical_left_coronary_arterial_system_stenosis.html 89 BMS DES N/A Everolimus, Zotarolimus, Paclitaxel, Sirolimus Early Restenosis Higher Lower Late In-stent Thrombosis Lower Higher Drugs Mortality Same Same 12 months 12 months ACS – Triple antiplatelet therapy (Warfarin, INR 2-3 + Aspirin 81mg + Clopidogrel 75mg ) 1 month 3-6 months (3 for –limus and 6 for –taxel stents) Elective PCI – DAPT (aspirin 81 mg + clopidogrel 75 mg) 1 month, rec for 12 months 3-6 months, rec for 12 months (3 for –limus and 6 for –taxel stents) ACS – DAPT (aspirin 81 mg + ticagrelor or clopidogrel) Jessica Louie, PharmD, APh, BCCCP 90 ¡ Arterial grafts § Left internal mammary artery (LIMA) § Radial artery ¡ Venous grafts § Saphenous vein 91 92 23 West Coast University, School of Pharmacy ¡ Spring 2024 ¡ Factors favoring CABG § Diabetes § EF < 50% § Significant Left Main stenosis ¡ § Significant proximal LAD stenosis § 3 vessel disease ¡ ¡ ¡ ¡ ¡ ¡ AB, a 73 y.o. WF, is brought to the ED complaining of substernal chest pressure that radiates to her neck that has lasted for the last 25 minutes The pain occurred while walking and was not relieved by rest or by taking 2 NTG tablets. She reports having a similar pain 6 hours ago that resolved after taking 3 NTG. PMH: DM, HTN, Vitals: BP 149/75, HR 103, RR 18, O2 96%, T 37.7 Home Meds: ASA 81mg, lisinopril 20mg PO daily, metformin 1000mg PO BID, glipizide 5mg PO daily FHx: Mother – MI at 43, Father – DM, HTN SH: Tobacco 1ppd x 60yr, denies EtOH/drugs, retired Labs: TnT < 0.01, TC 215mg, TG 125mg, HDL 36, LDL 154, SCr 0.85 EKG: ST depression V3-V6 93 94 DiPiro et al. (2023) Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw-Hill. Chapter 34 ¡ 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation. 2021;144:e368–e454. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001029 § ¡ Risk factors for ACS? ¡ Classification of ACS? ¡ Level of risk for this patient? ¡ What therapies to start now? Amsterdam EA, Wenger NK et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST Elevation Acute Coronary Syndromes: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:344-426. http://circ.ahajournals.org/content/130/25/e344.full.pdf+html ¡ O’Gara PT, Kushner FG, et al. 2013 ACCF/AHA Guideline for the Management of STElevation Myocardial Infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. JACC. 2013;61:78-140. http://content.onlinejacc.org/article.aspx?articleid=1486115 ¡ 95 Jessica Louie, PharmD, APh, BCCCP 96 24 West Coast University, School of Pharmacy Spring 2024 Thank you for your attention ANY QUESTIONS??? Jessica Louie, PharmD, APh, BCCCP jLouie@westcoastuniversity.edu Jessica Louie, PharmD, APh, BCCCP 97 25