Pravastatin-Aspirin Introduction

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Pravastatin-AspirinIntroduction

• Todd Baumgartner, MD, MPH
• Vice President Regulatory Sciences
• Pharmaceutical Research InstituteBristol-Myers
  Squibb

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Pravastatin-Aspirin Chronology

• June 2001
• Original application filed
• January 18
• Initial Cardio-Renal Drugs Advisory Committee
  Meeting
• February - May
• Discussions with FDA on remaining issues
• May 8
• Revised application filed

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Contents of Original Pravastatin-Aspirin NDA

• Meta-analysis of 5 secondary prevention trials
  demonstrating efficacy, safety and independent
  contribution of individual components
• Pharmacokinetic study demonstrating no PK
  interactions

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Pravastatin-Aspirin Advisory Committee Jan 18,
2002

• General agreement
• a population could be identified for which the
  combination product would be indicated
• meta-analysis demonstrated individual
  contribution to the beneficial cardiovascular
  outcomes in the secondary prevention population
• choice of the two doses of aspirin (81mg and
  325mg)

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Issues To Be Discussed Today

• Choice of pravastatin doses to be offered
• Potential for excessive bleeding should
  pravastatin-aspirin not be discontinued prior to
  surgery
• Potential for inappropriate discontinuation of
  pravastatin
• Concern over inappropriate use in a non-indicated
  population

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Pravastatin-Aspirin Proposed Secondary
Prevention 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

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Experts Available to Committee

• Jerome L. Avorn, MD
• Associate Professor of Pharmacoepidemiology,
  Harvard Medical School
• Donald A. Berry, PhD
• Professor and Chair of Biostatistics, University
  of Texas, M.D. Anderson Cancer Center
• Bernard R. Chaitman, MD
• Professor of Medicine, St. Louis University
• Lawrence J. Dacey, MD
• Associate Professor of Surgery, Dartmouth
  Hitchcock Medical Center, NH

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Experts Available to Committee

• Charles H. Hennekens, MD, DrPH
• Professor of Medicine, Epidemiology and Public
  Health, University of Miami School of Medicine,
  FL
• Thomas A. Pearson, MD, PhD, MPH
• Professor and Chair of Community Medicine,
  University of Rochester, NY
• Marc A. Pfeffer, MD, PhD
• Professor of Medicine, Brigham Womens, Boston
• Eric J. Topol, MD
• Chair of Cardiovascular Medicine, Cleveland
  Clinic

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Agenda

• Todd Baumgartner, MD, MPH
• Introductory remarks
• Rene Belder, MD
• Pravastatin doses and rationale
• Aspirin safety considerations
• Temporary discontinuation of statin therapy
• Fred Fiedorek, MD
• Pravastatin-aspirin Context and rationale