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Management of Acute Coronary Syndrome

Management of Acute Coronary Syndrome. Worldwide Statistics. Each year: > 4 million patients are admitted with unstable angina and acute MI > 900,000 patients undergo PTCA with or without stent. Myocardial Ischemia. Spectrum of presentation silent ischemia exertion-induced angina

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Management of Acute Coronary Syndrome

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  1. Management of Acute Coronary Syndrome

  2. Worldwide Statistics Each year: • > 4 million patients are admitted with unstable angina and acute MI • > 900,000 patients undergo PTCA with or without stent

  3. Myocardial Ischemia • Spectrum of presentation • silent ischemia • exertion-induced angina • unstable angina • acute myocardial infarction

  4. Cumulative 6-month mortality from ischemic heart disease 25 N = 21,761; 1985-1992 Diagnosis on adm to hosp 20 15 Deaths / 100 pts / month Acute MIUnstable anginaStable angina 10 5 0 0 1 2 3 4 5 6 Months after hospital admission Duke Cardiovascular Database

  5. Ischemic Heart Diseaseevaluation • Based on the patient’s • history / physical exam • electrocardiogram • Patients are categorized into 3 groups • non-cardiac chest pain • unstable angina • myocardial infarction

  6. Acute Coronary Syndrome HistoryPhysical Exam Ischemic DiscomfortUnstable Symptoms No ST-segmentelevation ST-segmentelevation ECG Unstable Non-Q Q-Waveangina AMI AMI AcuteReperfusion

  7. Acute Coronary Syndrome • The spectrum of clinical conditions ranging from: • unstable angina • non-Q wave MI • Q-wave MI • characterized by the common pathophysiology of a disrupted atheroslerotic plaque

  8. Unstable AnginaAnti-platelet Therapy • Abciximab • EPIC Trialeffective in preventing death, MI, and abrupt closure associated with coronary angioplasty (see also EPIC slides) • EPISTENT Trial

  9. Unstable AnginaAnti-platelet Therapy • Abciximab • CAPTURE • At 30 days, there was a 29% reduction in the primary composite endpoint of death, MI, or urgent revascularization in the abciximab group • At 6 months, this benefit was not evident Lancet 1997;349:1429-1435

  10. Unstable AnginaAnti-platelet Therapy • Tirofiban • PRISM(Platelet Receptor Inhibition for Ischemic Syndrome Management) • 3,200 patients with unstable angina were treated with either heparin or tirofiban • At 48 hours, there was significant risk reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. The benefit was lost at 30 days. N Engl J Med 1998;338:1498-505

  11. Unstable AnginaAnti-platelet Therapy • Tirofiban • PRISM -PLUS(Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms) • randomized 1,915 patients with UA and non-Q-MI to tirofiban alone, heparin alone, or a combination of the two (all received aspirin) N Engl J Med 1998;338:1488-97

  12. Unstable AnginaAnti-platelet Therapy • Eptifibatide • PURSUIT (Platelet IIb/IIIa Underpinning the Receptor for Suppression of Unstable Ischemia Trial) • ~11,000 patients admitted with unstable angina or non-Q-wave myocardial infarction • a broad-based trial encompassing a variety of clinical practices and practice styles NEJM 1998;339:436-443

  13. Unstable AnginaAnti-platelet Therapy • Eptifibatide PURSUIT • randomized to eptifibatide or placebo; all patients received aspirin and heparin • significantly reduced the risk of death and MI at 30 days from 15.7% to 14.2%, a 9% risk reduction NEJM 1998;339:436-443

  14. Platelet Inhibition and Bleeding Time IMPACT II PURSUIT 135 / 0.5 180 / 2.0 Inhibition of platelet aggregation 15 minutes after bolus 69% 84% at steady state 40-50% >90% 4h after infusion discontinuation <30% <50% Bleeding-time prolongation at steady state <5x <5x 6h after infusion discontinuation 1x 1.4x

  15. Fibanincidence of intracranial bleeding Treatment (%) Study Compound Placebo Active Heparin RESTORE Tirofiban 0.3 0.1 EPIC Abciximab 0.3 0.1 0.4 EPILOG Abciximab 0.0 0.1 IMPACT II Integrelin 0.07 0.07 0.15 Bolus Bolus + Infusion Low dose High dose The EXCITE Trial Investigators

  16. Unstable AnginaAnti-platelet Therapy • Summary • the four “P trials” (PRISM, PRISM-PLUS, PARAGON, PURSUIT) • all show reduction of death rate between1.3% and 3.4% - in addition to the benefit of aspirin • useful in the management of patients with unstable angina and MI without ST elevation

  17. Unstable AnginaAnti-coagulant Therapy • Heparin • recommendation is based on documented efficacy in many trials of moderate size • meta-analyses (1,2) of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding • titrate PTT to 2x the upper limits of normal 1. Circulation 1994;89:81-88 2. JAMA 1996;276:811-815

  18. Unstable AnginaAnti-coagulant Therapy • Low-molecular-weight heparinadvantages over heparin: • better bio-availability • higher ratio (3:1) of anti-Xa to anti-IIa activity • longer anti-Xa activity, avoid rebound • induces less platelet activation • ease of use (subcutaneous - qd or bid) • no need for monitoring

  19. ESSENCE Trialincidence of death, MI, or recurrent angina Day 14 Day 30 23.3% 19.8% 19.8% P=0.016 16.6% P=0.019 n=1564 n=1607 n=1564 n=1607 heparin Lovenox heparin Lovenox N Eng J Med 1997;337:447-452

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