Annual Patient Admissions for Acute Coronary Syndromes 1.4 MM Non-ST elevation ACS 0.6 MM ST-elevation MI ~ 2.0 MM patients admitted to CCU or telemetry annually

Current Management Goals in Treating Acute Coronary Syndromes Presumed prognosis: very high risk of in-hospital death Treatment goal: prevent death by restoring coronary blood flow Fibrinolytic therapy Direct PCI Presumed prognosis: low risk of in-hospital death, unless MI develops Treatment goal: stabilize with aspirin heparin & monitor for MI development + Cardiac enzymes – Cardiac Enzymes Scheduled PCI Manage medically Low - risk features High- risk features

1.0%  ( P  0.001) 1.9%  ( P  0.01) 11.5% 9.6% 7.3% 6.3% Heparin % death at 30 days (n=60,000) 1 (n=30,647) 2 Pooled thrombolytics Accelerated alteplase Streptokinase 1. Fibrinolytic therapy trialists’ collaborative group et al. Lancet.1994; 343: The GUSTO investigators. N Engl Med. 1993; 329: Reduction in Mortality Associated with Fibrinolytic Therapy for ST Elevation MI

6-month Mortality for Acute Coronary Syndromes T-wave inversion ACS ST  ACS Granger CB et al. J Am Coll Cardiol. 1998; 31:79A. % Cumulative mortality at 6 months ST  MI with fibrinolytics

Incidence of Adverse Outcomes in Non-ST Elevation ACS Patients Treated with Aspirin Plus Heparin Incidence of death or (re)MI 9.8% 3.2% 1.9% 1.7% 1.9% 2.9% 0-7 days  7-30 days > days Greenbaum AB et al. Circulation. 1998; Suppl I: I-630 Cumulative mortality rate: 1.7% Cumulative mortality rate: 3.6% Cumulative mortality rate: 6.5%

18.3% 5.5% 12.8%  (P=0.0001) Patients with MI within 72 hours (n=593) Patients without MI within 72 hours (n=8,868) Days following randomization % cumulative mortality Cumulative Mortality in Patients Experiencing MI During Hospitalization for Non-ST Elevation ACS Fintel DJ et al. J Am Coll Cardiol. 2000; 35A: A

3.9% 8.0% 9.0% 10.9% 14.9% 20.9% Normal  1-2 *  2-3 *  3-5 *  5-10 *  10* % Congestive Heart Failure/ Cardiogenic Shock at 30 days * x upper limit of normal 4.9% 5.7% 9.2% 12.6% 14.5% 19.9% % Death at 6 months Relationship Between Extent of Myocardial Necrosis and Long-Term Morbidity and Mortality (n=5,681)(n=1,098)(n=294)(n=302)(n=249)(n=211) Alexander JH et al. Circulation. 1999; Suppl 1: CK-MB levels during hospitalization Normal  1-2 *  2-3 *  3-5 *  5-10 *  10 * CK-MB levels during hospitalization

Incidence of MI Prior to PCI in Patients with Non-ST Elevation ACS 8.9% 2.2% PCI within 2-3 days PCI within 24 hours % MI prior to PCI Roe MT, et al. J Am Coll Cardiol. 2000; 35: 40A. Post-randomization analysis

Cumulative Mortality at 6 Months in Patients Experiencing MI Prior to PCI 15.2% 3.5% 11.7%  (P=0.001) No MI prior to early PCI (n=1,204) MI prior to early PCI (n=46) Months following randomization % cumulative mortality Post-randomization analysis Fintel DJ et al. J Am Coll Cardiol. 2000; 35A: A375.

ST  49% Mixed ST  & ST  20% T-wave inversion 31% % Patients with non-ST  ACS ST Depression is The Most Common ECG Abnormality Noted in Patients Presenting with Non-ST Elevation ACS Savonitto S, et al. J Am Med Assoc. 1999; 281:

% 8% 6% 4% 2% T-wave inversion 3.4% ST  6.8% ST  8.9% Days from randomization % Cumulative Mortality 2 ST Depression: Indicates Increased Risk for Long-term Mortality Savonitto S, et al. J Am Med Assoc. 1999; 281:

Patients with ST  : Likely to Have Higher-risk Medical Histories than Patients with ST  Savonitto S, et al. J Am Med Asoc. 1999; 281:

ST Depression Signifies Likelihood to Require High-risk Revascularization Savonitto S, et al. J Am Med Asoc. 1999; 281:

Percent of Patients Presenting with Non-ST Elevation ACS who Present with Elevated CK or CK-MB Lab Values The PURSUIT trial investigators. N Engl J Med. 1998; 339: The PRISM-PLUS investigators. N Engl J Med. 1998; 338: The TIMI IIIb investigators. Circulation. 1996; 335:

Relationship Between Elevated Cardiac Enzymes at Presentation and Long-term Risk for Death or (re)MI 19.0% 13.0% 13.1% 8.9%  CK-MB (n=4,308)  CK-MB (n=921) Normal CK-MB (n=5,129) Normal CK-MB (n=7,438) PURSUIT 1 GUSTO IIb 2 % death or (re)MI at 30 days 1,2 1. The PURSUIT trial investigators. N Engl J Med. 1998; 339: Savonitto S, et al. J Am Med Asoc. 1999; 281:

Correlation Between Elevated Cardiac Enzymes at Presentation and Long-term Mortality + Cardiac Troponin T at Baseline (n=559) 14.1% 4.5% – Cardiac Troponin T at Baseline (n=474) % mortality at 1 year Newby LK et al. Circulation. 1998; 98: P<0.0001

Relationship Between Degree of Troponin Elevation and Likelihood for Long-term Mortality Antman EM, it al. N Engl J Med. 1996; 335: % mortality at 42 days <0.4<1.0<2.0<5.0<9.0  Troponin levels

Risk of Death/Re-MI in Patients Presenting with ST  and Elevated Cardiac Enzymes at Presentation 14.8% 8.0% 21.7% 14.6% ST  with CK-MB  ST  with normal CK % death % death + re-MI Events at 6 months Savonitto S, et al. J Am Med Asoc. 1999; 281: ST  with CK-MB  ST  with normal CK

Predictors of Increased Risk of Death or MI at 30 Days from the PURSUIT Study The PURSUIT trial investigators. N Engl J Med. 1998; 339: