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QUARTERLY FOCUS ISSUE: PREVENTION/OUTCOMES: CLINICAL RESEARCH: LIPID-LOWERING AND TOTAL CARDIOVASCULAR BURDEN

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

TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Manuscript received May 7, 2009; revised manuscript received September 30, 2009, accepted October 12, 2009.

^_* Reprint requests and correspondence: Dr. Christopher P. Cannon, TIMI Study Group, 350 Longwood Avenue, First Floor, Boston Massachusetts 02115 (Email: cpcannon{at}partners.org).

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.

Key Words: statin • acute coronary syndrome • lipid lowering • clinical trial

Abbreviations and Acronyms   ACS = acute coronary syndrome   CRP = C-reactive protein   LDL-C = low-density lipoprotein cholesterol   MI = myocardial infarction   UA = unstable angina

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