Pravastatin-Aspirin Introduction

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					  Pravastatin-Aspirin
     Introduction

Todd Baumgartner, MD, MPH
       Vice President
     Regulatory Sciences
Pharmaceutical Research Institute
     Bristol-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 & Women’s, 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

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