Download from Slide 1 AGGRASTAT ® † (tirofiban, MSD) to ZOCOR ™ † (simvastatin, MSD) (A to Z) Trial Results from the AGGRASTAT Phase † Trademarks of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Download from Slide 2 Background Enoxaparin, a LMWH, has been shown to be superior to UFH in ACS populations in the absence of GP IIb/IIIa inhibitors –Most trials used conservative management and predated widespread use of GP IIb/IIIa inhibitors GP IIb/IIIa inhibitors are recommended for high-risk ACS patients in whom an invasive strategy is planned Small trials suggest additional benefit of enoxaparin over UFH when used in combination with GP IIb/IIIa inhibitors LMWH=low-molecular-weight heparin; UFH=unfractionated heparin; ACS=acute coronary syndrome; GP=glycoprotein

Download from Slide 3 Trial Objectives A-Phase To assess the safety profile and efficacy of enoxaparin compared with UFH in patients with NSTE ACS who received concomitant therapy with AGGRASTAT ® † (tirofiban, MSD) and ASA Z-Phase To evaluate the efficacy and tolerability of early use of aggressively-dosed treatment with ZOCOR ™ † (simvastatin, MSD) compared with an accepted care regimen NSTE=non–ST-elevation; ASA=acetylsalicylic acid Adapted from Blazing MA et al Am Heart J 2001;142(2):211–217; Blazing MA et al JAMA 2004;292(1):55–64. † Trademarks of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Download from Slide 4 Participating Countries 340 enrolling sites in 41 countries Adapted from Blazing MA et al JAMA 2004;292(1):55–64.

Download from Slide 5 Eligibility Criteria Inclusion criteria –Chest pain at rest for  10 minutes –Dynamic ST changes of at least 0.5 mm or positive cardiac marker (troponin, CK-MB, or CK  2  ULN) –21 to 80 years of age Major exclusion criteria –Prior use of statin or other lipid-lowering agent –Use of GP IIb/IIIa agent other than AGGRASTAT ™ † (tirofiban, MSD) –>24 hours of prior UFH or >2 doses enoxaparin –High risk of bleeding, prior thrombocytopenia –Abnormal creatinine and ALT/AST values CK-MB=creatine phosphokinase muscle band; ULN=upper limits of normal; ALT=alanine aminotransferase; AST=aspartate aminotransferase Adapted from Blazing MA et al Am Heart J 2001;142(2):211–217; Blazing MA et al JAMA 2004;292(1):55–64. † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Download from Slide 6 A-Phase Study Design 30 days Randomize –24 hr Chest pain AGGRASTAT ®† (tirofiban, MSD) + ASA Invasive or conservative care per local practice n=2026 n=1961 Enoxaparin 1 mg/kg q12h UFH Weight-adjusted Z Z Treat and evaluate for Z-Phase n=2018 n=1952 N=3987 Primary endpoint UA/NSTEMI=unstable angina/non–ST-elevation myocardial infarction Adapted from Blazing MA et al Am Heart J 2001;142(2):211–217; Blazing MA et al JAMA 2004;292(1):55–64. † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. NSTE ACS Final A-Phase visit 7 days Min 0 hrMax 120 hr

Download from Slide 7 A-Phase Trial Design and Safety Profile Selection of management strategy (invasive or conservative) left to investigator at randomization –Crossover from enoxaparin to UFH allowed for invasive procedures Bleeding events recorded via two methods –Investigator assessment on case record form and independent review of hemoglobin values –Units of packed red blood cells transfused –Bleeding events categorized by change in hemoglobin levels using TIMI criteria TIMI=Thrombolysis In Myocardial Infarction Adapted from Blazing MA et al Am Heart J 2001;142:211–217; Blazing MA JAMA 2004;292(1):55–64.

Download from Slide 8 Primary –Composite of death, MI, and refractory ischemia (+ marker and/or ECG changes) within 7 days of start of AGGRASTAT ® † (tirofiban, MSD) therapy Secondary –Death, MI, refractory ischemia, urgent coronary revascularization, and DMCMIE evaluated at 7 days individually and as a composite Tertiary –All primary and secondary endpoints and readmission for ACS evaluated at 48 hours and 30 days Study Endpoints DMCMIE=documented multiple clinical myocardial ischemic events † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Download from Slide 9 Median age (years) Men 71.4% 71.2% White 85.6% 85.2% Diabetes 19.5% 18.2% Hypertension 50.0% 52.3% Current smoking 36.0% 39.4% Prior MI 17.8% 18.3% Index MI* 74.5% 72.8% ST change >1 mm 70.3% 71.9% UFH** 37.3% 38.5% LMWH** 34.3% 34.2% Baseline Characteristics *Investigator determined; **Use before randomization Adapted from Blazing MA et al JAMA 2004;292(1):55–64. EnoxaparinUFH Characteristics(n=2026)(n=1961)

Download from Slide 10 Hospital Course EnoxaparinUFH (n=2026)(n=1961) Median study drug administration (hours) Planned early aggressive strategy PCI or catheterization at  108 hrs Concomitant therapies at discharge ACEI ARB ASA Beta-blocker CCB Diuretic Nitrate PCI=percutaneous coronary intervention; ACEI=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CCB=calcium channel blocker Adapted from Blazing MA et al JAMA 2004;292(1):55–64.

Download from Slide 11 Primary Endpoint—Overall UFH (n=1952) Enoxaparin (n=2018) Days from enrollment Primary endpoint (%) % (169 events) 9.4% (184 events) HR 0.88 (95% CI, 0.71–1.08) HR=hazard ratio; CI=confidence interval Adapted from Blazing MA et al JAMA 2004;292(1):55–64. Composite of death, MI, and refractory ischemia 7

Download from Slide 12 Secondary Endpoints at 7 Days DMCMIE=documented multiple clinical myocardial ischemic events *Indicates chest pain requiring change in therapy but not meeting criteria for refractory ischemia Adapted from Blazing MA et al JAMA 2004;292(1):55–64. Secondary composite –1.05 Death –2.38 MI –1.13 Refractory ischemia –1.10 Urgent revascularization –1.29 DMCMIE* –0.98 % of Patients EnoxaparinUFHHR95% CI

Download from Slide 13 Subgroup Analyses Enoxaparin UFH Primary hypothesis <65 years  65 years Diabetes No diabetes Invasive Conservative Age % of Patients HR (95% CI) Adapted from Blazing MA et al JAMA 2004;292(1):55–64. Favors enoxaparinFavors UFH

Download from Slide 14 Subgroup Analyses (continued) Primary hypothesis No ST change ST change (  1 mm) Elevated troponin (>ULN) Normal troponin 5– –2 3–4 Enoxaparin UFH % of Patients TIMI risk score HR (95% CI) Adapted from Blazing MA et al JAMA 2004;292(1):55– Favors enoxaparinFavors UFH

Download from Slide Hour Bleeding Events TIMI major=hemoglobin drop >5 mg/dL, intracranial bleed, or pericardial bleed TIMI minor=hemoglobin drop >3 or  5 mg/dL with an identified site; hemoglobin drop >4 or  5 mg/dL without an identified site or hematuria, hematochezia, or hematemesis Adapted from Blazing MA et al JAMA 2004;292(1):55–64. % of Patients TIMI majorTIMI major or minor Transfusion p=0.05 UFH (n=1965) Enoxaparin (n=1940) UFH (n=1965) Enoxaparin (n=1940) UFH (n=1965) Enoxaparin (n=1941)

Download from Slide 16 Conclusions In patients with high-risk NSTE-ACS treated with AGGRASTAT™ † (tirofiban, MSD) and ASA, enoxaparin is an effective noninferior alternative to UFH Overall rates of bleeding, transfusion, and thrombocytopenia were low in both heparin groups given AGGRASTAT and ASA Adapted from Blazing MA et al JAMA 2004;292(1):55–64. † Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Download from Slide 17 References

Download from Slide 18 A-Phase of the AGGRASTAT ® † (tirofiban, MSD) to ZOCOR ™ † (simvastatin, MSD) (A to Z) Trial Before prescribing, please consult manufacturers’ prescribing information. Merck does not recommend the use of any product in any different manner than as described in the prescribing information. Copyright © 2004 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved ARS 2004-W-6323-SS Printed in USA VISIT US ON THE WORLD WIDE WEB AT † Trademarks of Merck & Co., Inc., Whitehouse Station, NJ, USA.