* Based on post hoc analysis of individual outcome events (N=19,185). 1 Data on file, Sanofi Pharmaceuticals, Inc. 2 Gent M. Circulation. 1997; 96 (suppl): I-467. Abstract CAPRIE Study Risk Reduction in MI Outcome Events (Fatal and Nonfatal MI) Event Rate for MI (fatal or nonfatal) RelativeRiskReduction (P=0.008) 2* 19.2% Aspirin 1 3.6% PLAVIX 1 2.9%

CAPRIE Study Risk Reduction in MI Outcome Events (Fatal and Nonfatal MI) Months of Follow-Up Event Rate for MI (%) (fatal or nonfatal) Clopidogrel Aspirin Relative Risk Reduction 19.2% * Based on post hoc analysis of individual outcome events (N=19,185). 1 Data on file, Sanofi Pharmaceuticals, Inc. 2 Gent M. Circulation. 1997;96(suppl):I-467. Abstract Aspirin 1 3.6% 2.9% Clopidogrel 1 (P = 0.008) 2* 4

CAPRIE Steering Committee. Lancet. 1996;348: Data on file, Sanofi Pharmaceuticals, Inc. CAPRIE Study Additional Manifestations of Atherosclerosis Prior to Study Entry Prevalence (%) in the CAPRIE population * Does not include the qualifying event/condition. (n=5833) (n=3205) (n=1689) (n=1534) (n=851)

CAPRIE Steering Committee. Lancet. 1996;348: Data on file, Sanofi Pharmaceuticals, Inc. CAPRIE Study Additional Cardiovascular Risk Factors At Study Entry Prevalence (%) in the CAPRIE Prevalence (%) in the CAPRIEpopulation (n=9885) (n=7904) (n=5668) (n=3881)

Current Labeling for Oral Antiplatelet Agents Plavix Package Insert. Ticlid Package Insert. Aspirin Professional Labeling. Recent Ischemic Stroke Yes No PlavixTiclidAspirin Recent Myocardial Infarction Established PAD Yes No Yes No

IS IS MI MI PAD PAD Total Total Aspirin better Clopidogrel better Aspirin better Clopidogrel better IS (fatal or non-fatal) MI (fatal or non-fatal) (fatal or non-fatal) Vascular death Total Aspirin better Clopidogrel better CAPRIE Study MI Paradox: Subgroups vs. Outcomes Relative Risk Reduction* by Qualifying Subgroup 1 Relative Risk Reduction of Individual Outcomes in Total Population 7.3% 5.2% % 3‡ 7.6% % 23.8% 8.7% 1† *Cluster of IS, MI, or vascular death † p=0.043 ‡ p= CAPRIE Steering Committee. Lancet.1996; 348: Easton JD. Neurology July; P Abstract. 3 Gent M. Circulation. 1997; 96(8 supple): I-467 Abstract. 8.7% 1†

CAPRIE Study Risk Reduction in MI Outcome Events (Fatal and Nonfatal MI) Months of Follow-Up Event Rate for MI (%) (fatal or nonfatal) Clopidogrel Aspirin Relative Risk Reduction 19.2% * Based on post hoc analysis of individual outcome events (N=19,185). 1 Data on file, Sanofi Pharmaceuticals, Inc. 2 Gent M. Circulation. 1997;96(suppl):I-467. Abstract Aspirin 1 3.6% 2.9% Clopidogrel 1 (P = 0.008) 2* 4

CAPRIE Study Net Benefit of Clopidogrel: Prevention of Atherosclerotic Events and Major Bleeding Complications Primary Hemorrhagic Intracranial Cluster*DeathHemorrhage Total EventsRRR ‡‡ Clopidogrel Aspirin Easton JD. American Academy of Neurology April; 50(4): Abstract. SafetyEndpoints * First outcome event of ischemic stroke, myocardial infarction, and vascular death ‡‡ Relative Risk Reduction (p=0.025) 9.5% Net Benefit EfficacyEndpoint

ObjectiveTo estimate the event rates expected in actual practice vs. CAPRIE population. Patient Population9,072 patients with MI, ischemic stroke, or PAD in Saskatchewan, Canada. ResultsFirst Hospitalized Event Rate ASA Clopidogrel MI6.4%1.9% Stroke5.8%2.6% All cause death9.7%3.1% ConclusionIschemic events occurred between times more often in actual practice. Caro J. Euro Heart J. 1998;19: P1263 Abstract. CAPRA Analysis Caprie Actual Practice Rates Assessment Translates to 15 additional events prevented by clopidogrel over aspirin per 1,000 patients treated per year.

CAPRIE Study Consistency of Clopidogrel Benefit Across Atherosclerotic-Related Events RRR(95% CI) Single endpoints: IS 5.2( ) MI 19.2( ) Vascular death7.6( ) Combined endpoints of vascular events: IS, MI10.9( ) TIA, hospitalization due to angina7.5( ) IS, MI, TIA, hospitalization due to angina 7.9( ) Combined endpoints of major vascular events: Any stroke*, MI, vascular/hemorrhagic9.5( ) death (net benefit cluster) Any stroke, MI, death from any cause7.0( ) Rupprecht HJ. Euro Heart J. 1998;19: P484 Abstract. * Ischemic or hemorrhagic

Guillot F. American Heart Association; 1998 Nov. Abstract Epidemiology Estimated Prevalence of Ischemic Stroke and Myocardial Infarction in North America and Europe

Cirrhosis Does Not Affect the Pharmacokinetics or Pharmacodynamics of Clopidogrel Cmax Tmax AUC Study Group (ng/mL) (hr) (range) gxhr/mL Cirrhosis Day ± (0.5, 2.5) ± Controls Day ± (0.5, 2.0) ± Cirrhosis Day ± (0.5, 1.5) ± Controls Day ± (0.5, 1.5) ± Smith Ul et al. Euro Heart J. 1998;19: P490 Abstract. No significant difference in mean % inhibition of aggregation at day 10 (49.2% ± 38.6 vs. 66.7% ± 7.5) Prolongation of bleeding time was comparable at day 10 (1.64 ± 0.49 vs 1.54 ± 0.87) No dosage adjustment of clopidogrel is necessary in mild to moderate liver impairment.

Cocchereri S. Euro Heart J. 1998;19: P1268 Abstract. CAPRIE Study Influence of Atherosclerotic History on Ischemic Event Rates Event Rate (%) (IS, MI, Vascular Death) Qualifying PAD + any history* Coronary disease only Cerebro- vascular disease only PAD Only Qualifying MI + any history* Qualifying IS + any history* Disease in  2 beds * Any history of atherosclerotic disease in any of the three vascular beds

Cocchereri S. Euro Heart J. 1998;19: P1268 Abstract. CAPRIE Study Influence of Peripheral Arterial Disease History on Ischemic Event Rates Qualifying PAD group + any history* PAD Only * Any history of atherosclerotic disease disease in any of the three vascular beds Disease in  2 beds Event Rate, % (IS, MI, Vascular Death)

Cocchereri S. Euro Heart J. 1998;19: P1268 Abstract. CAPRIE Study Influence of Stroke History on Ischemic Event Rates Event Rate, % (IS, MI, Vascular Death) Cerebrovascular disease only Qualifying IS group + any history Disease in  2 beds * Any history of atherosclerotic disease in any of the three vascular beds

CAPRIE Study Proven Safety Profile of Clopidogrel CAPRIE Steering Committee. Lancet. 1996;348: Data on file, Sanofi Pharmaceuticals, Inc. GI hemorrhage 1, 2 Hospitalization due to GI 2 hemorrhage GI ulcers 2 Intracranial hemorrhage 2 (n=191) (n=255) (n=71) (n=104) (n=65) (n=110) (n=34) (n=47)

Revascularization Efficacy of Clopidogrel in PTCA Objective Evaluate efficacy and tolerance of a loading dose of clopidogrel. Patients n=20 (age - 56 ± 11years) with stable angina scheduled for PTCA Treatment ASA 325 mg/day or clopidogrel 375 mg in in the morning of procedure followed by 75 mg/day maintenance. Heparin  24 hours after PTCA given to all patients. Savcic M et al. Eur Heart J. 1995;16:suppl:417 Abstract. 2h6h8h24h Clopidogrel17 ± 18%26 ± 21%*30 ± 26%*20 ± 10%* ASA5 ± 9%-2 ± 8%-3 ± 12%-8 ± 19% Results Mean %platelet Inhibition (5  M ADP) Events 1 dissection † 3 dissections † 1 subacute occlusion * p = 0.01 † requiring stenting Conclusion: Loading doses of 375 mg clopidogrel in combination with heparin was well-tolerated and induced a rapid antiaggregatory effect that was safe and superior to aspirin.