4.7 Article

Reduction in Recurrent Cardiovascular Events With Intensive Lipid-Lowering Statin Therapy Compared With Moderate Lipid-Lowering Statin Therapy After Acute Coronary Syndromes From the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Trial

Journal

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Volume 54, Issue 25, Pages 2358-2362

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2009.10.005

Keywords

statin; acute coronary syndrome; lipid lowering; clinical trial

Funding

  1. Bristol-Myers Squibb
  2. Accumetrics
  3. AstraZeneca
  4. Bristol-Myers Squibb/Sanofi Partnership
  5. GlaxoSmithKline
  6. Intekrin Therapeutics
  7. Merck
  8. Merck/Schering-Plough Partnership
  9. Novartis
  10. Takeda

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Objectives In addition to reducing first events in patients after an acute coronary syndrome (ACS), we hypothesized that high-dose atorvastatin 80 mg would also reduce recurrent cardiovascular events, and therefore total events, compared with pravastatin 40 mg during the 2-year follow-up. Background In the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial, more intensive lipid lowering with high-dose atorvastatin reduced the first occurrence of the primary end point (death, myocardial infarction, unstable angina requiring rehospitalization, stroke, or revascularization >= 30 days) compared with moderate lipid lowering with pravastatin. Methods Poisson regression analysis was performed to compare the number of occurrences of the primary end point between high-dose atorvastatin and pravastatin in the PROVE IT-TIMI 22 trial. Results As previously reported, first primary end point events were reduced by 16% with atorvastatin 80 mg versus pravastatin 40 mg (n = 464 vs. n = 537, respectively; p = 0.005). Additional events were also reduced by 19% with atorvastatin 80 mg (n = 275 vs. n = 340, respectively; p = 0.009). Overall, there were 138 fewer primary efficacy events with atorvastatin 80 mg versus pravastatin 40 mg (n = 739 vs. n = 877, respectively; rate ratio: 0.85, 95% confidence interval: 0.77 to 0.94, p = 0.001). Conclusions Although analytic techniques commonly used in clinical outcomes trials censor patients who experience a component of the primary composite end point, total cardiovascular events are important to patients, clinicians, and health care payers. Maintaining low levels of low-density lipoprotein cholesterol is central to preventing additional atherosclerotic development and subsequent cardiovascular events. Atorvastatin 80 mg, a more intensive low-density lipoprotein cholesterol lowering agent, reduced both first and subsequent primary end point events compared with pravastatin 40 mg after ACS. (J Am Coll Cardiol 2009; 54: 2358-62) (C) 2009 by the American College of Cardiology Foundation

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