A-1 Introduction Pravastatin-Aspirin 7asdf Fred T. Fiedorek, M.D. Vice President, Clinical Design & Evaluation, Metabolics Pharmaceutical Research Institute Bristol-Myers Squibb

A-2 US 1998 Source: CDC / NCHS and the American Heart Association Total CVD Cancer Accidents Chronic Obstructive Pulmonary Disease Pneumonia/ Influenza Diabetes Mellitus Cardiovascular Disease: Far and Away the Leading Cause of Death

A-3 Deaths and Death Rates for CHD United States: 1979 – 98 Source: NHLBI Chartbook ,000 1, Years Deaths/ 100,000 Population (Lines) Deaths in Thousands (Bars) Age-Adjusted Death Rate

A-4 A Pravastatin-Aspirin Combination Will Facilitate… Accuracy and adherence: –Enhanced implementation of guidelines recommending both therapies –Enhanced assurance for health care providers  correct product  correct doses Enhanced convenience for patients –Decreased pill burden

A-5 Aspirin Label Aspirin is indicated in patients: –with a previous MI or unstable angina to reduce death and non-fatal MI –with chronic stable angina to reduce MI and sudden death –who have undergone revascularization procedures for a pre-existing condition –with a suspected acute MI to reduce vascular mortality –who have had ischemic stroke or transient ischemia of the brain due to fibrin platelet emboli to reduce death and non-fatal stroke

A-6 Pravastatin Label Secondary Prevention In patients with clinically evident coronary heart disease, pravastatin is indicated to: –reduce the risk of total mortality by reducing coronary death –reduce the risk of MI –reduce the risk of undergoing myocardial revascularization procedures –reduce the risk of stroke and stroke/TIA –slow the progression of coronary atherosclerosis

A-7 Pravastatin-Aspirin Proposed Indication Long-term management to reduce the risk of the following cardiovascular events in patients with clinically evident coronary heart disease: Death Non-fatal myocardial infarction Myocardial revascularization procedures Ischemic stroke

A-8 Pravastatin Contraindicated Hepatic Disease Hepatic Disease Aspirin 12.4 Million CHD Patients Pravastatin-Aspirin Patient Population Sources: ACC/AHA Guidelines 2001, 2001 Pharmametrics Database, Boston MA Eligible for Prava+Aspirin 10.4 Million PatientsContraindicated GI Hemorrhage GI Hemorrhage Peptic Ulcer Disease Peptic Ulcer Disease ASA sensitivity ASA sensitivity

A-9 Properties Required of Combination Product Different mechanisms of action of components No PK or PD interaction between components Acceptable safety and tolerability profile Appropriate dose combinations available Both components contribute independently to efficacy Addresses a medical need

A-10 BMS Consultant Panel Donald A. Berry, Ph.D. – Frank T. McGraw Memorial Chair of Cancer Research, University of Texas, M.D. Anderson Cancer Center Thomas A. Pearson, M.D., M.P.H., Ph.D. – Albert D. Kaiser Professor and Chair of Community and Preventive Medicine, University of Rochester School of Medicine Charles H. Hennekens, M.D. – Professor of Medicine and Epidemiology / Public Health, University of Miami School of Medicine Andrew Tonkin, M.D. – National Heart Foundation of Australia; Professor of Medicine, University of Melbourne; Principal Investigator of LIPID Trial Frank Sacks, M.D. – Harvard School of Public Health; Professor of Cardiovascular Disease Prevention Attending Physician, Hyperlipidemia Clinic, Brigham & Women’s Hospital

A-11 Speakers for This Morning Dr. René Belder Mechanism of action of components PK analysis Safety and tolerability of combination Dose combinations available Efficacy– based on individual trials Dr. Donald Berry Efficacy– based on meta-analyses Efficacy– presence of consistent benefit Dr. Thomas Pearson Medical Need