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Antiplatelet Interventions in Acute Coronary Syndromes

Antiplatelet Interventions in Acute Coronary Syndromes. Contents. Acute Coronary Syndromes: Tailoring Treatment to Level of Risk Thrombus Susceptibility and the Vulnerable Plaque: Relationship Between Inflammation and Thrombosis ACC/AHA UA/NSTEMI Guidelines: Role of GP IIb/IIIa Inhibitors

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Antiplatelet Interventions in Acute Coronary Syndromes

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  1. Antiplatelet Interventions in Acute Coronary Syndromes

  2. Contents • Acute Coronary Syndromes: Tailoring Treatment to Level of Risk • Thrombus Susceptibility and the Vulnerable Plaque: Relationship Between Inflammation and Thrombosis • ACC/AHA UA/NSTEMI Guidelines: Role of GP IIb/IIIa Inhibitors • Clinical Trials of GP IIb/IIIa Inhibition • Clinical Insights, Risk Stratification, and Enhancing Outcomes • GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence

  3. Acute Coronary Syndromes: Tailoring Treatment to Level of Risk

  4. US hospital discharges: Unstable angina/NSTEMI and STEMI Acute coronary syndromes 1.67 million hospital discharges UA/NSTEMI STEMI 1.17 million discharges per year 500,000 discharges per year STEMI = ST-elevation myocardial infarction (MI), or Q-wave MI NSTEMI = non–ST-elevation MI, or non–Q-wave MI AHA. Heart Disease and Stroke Statistics–2005 Update.

  5. ACC/AHA 2002 UA/NSTEMI guidelines: High-risk indicators for early invasive strategy Class I (Level of evidence: A) • Recurrent angina/ischemia on treatment • Elevated troponin levels • New ST-segment depression • Recurrent angina/ischemia with CHF symptoms, S3 gallop, pulmonary edema, worsening rales, new or worsening mitral regurgitation • High-risk noninvasive test results • Depressed LV function (EF <40%) • Sustained ventricular tachycardia • PCI within 6 months • Prior CABG Braunwald E et al. J Am Coll Cardiol. 2002;40:1366-74.

  6. Invasive Rx in ACS: Early and late mortality 7 trials, N = 9212 Inv (%) Cons (%) Favors routineinvasive Favors selectiveinvasive Mortality during hospitalization TIMI 3B 2.2 1.9 VANQWISH 4.5 1.3 MATE 0.9 3.3 FRISC II 1.1 0.9 1.4 0.7 TACTICS 1.6 4.5 VINO 0.7 RITA 3 1.6 OR 1.60, P = 0.007 1.8 1.1 Subtotal Mortality after discharge TIMI 3B 2.8 3.3 VANQWISH 13.4 11.7 10.0 6.9 MATE FRISC II 1.2 3.0 TACTICS 1.9 2.8 1.6 9.4 VINO RITA 3 5.2 7.3 OR 0.76, P = 0.01 Subtotal 3.8 4.9 0.1 0.2 0.5 1 2 5 10 Odds ratio (95% CI) Mehta SR et al. JAMA. 2005;293:2908-17.

  7. Invasive management of UA/NSTEMI meta-analysis: Subgroups 7 trials, N = 9212 Death or MI at follow-up Favorsroutineinvasive Favorsselective invasive Trial Selective (%) Odds ratio P Routine (%) Before 1999* 19.3 19.6 0.92 0.99 After 1999† 9.4 12.4 0.73 <0.001 0.69 14.0 Positive troponin‡ 10.0 0.001 Negative troponin 6.7 0.89 0.42 7.4 0.82 17.4 14.7 Marker positive 0.01 0.90 7.7 8.5 Marker negative 0.40 Overall 12.2 14.4 0.82 0.001 1.0 2.0 0.5 Odds ratio (95% Cl) *TIMI 3B, VANQWISH, MATE †FRISC II, TACTICS, VINO, RITA 3 ‡Data by troponin status available only in FRISC II, TACTICS, RITA 3 Mehta SR et al. JAMA. 2005;293:2908-17.

  8. RITA 3: Benefit of routine invasive strategy mainly in high-risk patients Randomized Intervention Trial of unstable Angina *Based on age, diabetes, prior MI, smoking, ST, pulse, grade 3/4 angina, sex, left bundle branch block, transient ST Fox KAA et al. Lancet. 2005;366:914-20.

  9. RITA 3: Greater benefit of early invasive strategy in men vs women with ACS n = 682 women, 1128 men with UA/NSTEMI Men Women 20 20 HR 1.09(95% CI 0.70–1.71) HR 0.61(95% CI 0.44–0.85) 16 16 Invasive Conservative Deathor MI(%) 12 12 8 8 Invasive Conservative 4 4 0 0 0 1 2 3 0 1 2 3 Time (years) Time (years) No. patients Invasive 545 491 354 189 350 316 228 125 Conservative 583 507 356 194 332 305 230 119 Clayton TC et al. Eur Heart J. 2004;25:1641-50.

  10. FRISC II: Men with ACS show greater benefit from early invasive strategy than women Fragmin and fast Revascularization during InStability in Coronary artery disease n = 749 women, 1708 men with UA/NSTEMI Men Women 20 20 Noninvasive (n = 834) 16 15.8% 16 Invasive (n = 348) 12.4% P < 0.001 12 Death or MI(%) 12 ns 10.5% 9.6% 8 8 Invasive (n = 874) Noninvasive (n = 401) 4 4 0 0 0 60 120 180 240 300 360 0 60 120 180 240 300 360 Time (days) Time (days) Lagerqvist B et al. J Am Coll Cardiol. 2001;38:41-8.

  11. Release of cardiac troponins and CK-MB in acute MI 50 Cardiac troponin after“classic” acute MI 20 CK-MB after acute MI 10 Multiples of the upper reference limit Cardiac troponin after“microinfarction” 5 2 Upperreference limit 1 0 0 1 2 3 4 5 6 7 8 Days after onset of acute MI Antman EM. N Engl J Med.2002;346:2079-82.

  12. In-hospital mortality higher with any degree of troponin elevation in NSTEMI patients CRUSADE: N = 23,298 7 6 5 In-hospital mortality (%) 4 3 2 1 0 0 1 2 3 4 5 6 7 8 9 10 Maximum troponin ratio Reference limit: maximum troponin ratio 0–1x upper limit of normal Roe MT et al. Arch Intern Med. 2005;165:1870-6.

  13. TIMI risk score for UA/NSTEMI • Age ≥65 years • ≥3 CAD risk factors* • Significant coronary stenosis • ST-segment deviation • Severe angina (≥2 anginal events in last 24 hours) • Daily use of aspirin in prior 7 days • Elevated serum cardiac markers† *Family history of CAD, hypertension, elevated cholesterol, diabetes, current smoker †Creatine-kinase MB and/or cardiac troponins Antman EM et al. JAMA. 2000;284:835-42.

  14. TIMI risk score in UA/NSTEMI 45 40.9 35 Death/MI/severe ischemia at 14 days (%) 26.2 25 19.9 13.2 15 8.3 4.7 5 0 0/1 2 3 4 5 6/7 Risk factors (n) n = 1957 ACS patients Antman EM et al. JAMA. 2000;284:835-42.

  15. Multimarker strategy: Identifying high-risk patients by troponin I, CRP, and BNP OPUS-TIMI 16 TACTICS-TIMI 18 6 6 14 13 P = 0.014 P < 0.001 30-day mortality relative risk 10 4 3.5 5.7 6 1.8 2 1 2.1 2 1 0 0 0 1 2 3 0 1 2 3 Elevated cardiac biomarkers (n) Elevated cardiac biomarkers (n) n = 67 150 155 78 504 717 324 90 BNP = B-type natriuretic peptide CRP = C-reactive protein Sabatine MS et al. Circulation. 2002;105:1760-3.

  16. Multimarker approach in ACS Acceleratedatherosclerosis Myocyte necrosis Troponin Hemodynamic stress Inflammation hs-CRP, CD40L BNP, NT-proBNP Vasculardamage A1C CrClMicroalbuminuria Blood glucose Independentpredictor of risk Useful in multimarker strategy Therapeuticimplication Biomarker Giugliano RP et al. J Am Coll Cardiol. 2005;46:906-19.

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