Author + information
- Received May 7, 2009
- Revision received September 30, 2009
- Accepted October 12, 2009
- Published online December 15, 2009.
- Sabina A. Murphy, MPH,
- Christopher P. Cannon, MD* (, )
- Stephen D. Wiviott, MD,
- Carolyn H. McCabe, BS and
- Eugene Braunwald, MD
- ↵*Reprint requests and correspondence:
Dr. Christopher P. Cannon, TIMI Study Group, 350 Longwood Avenue, First Floor, Boston Massachusetts 02115
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.
The TIMI Study Group received research grants from Bristol-Myers Squibb to conduct the PROVE IT–TIMI 22 trial. Dr. Cannon receives research grants/support from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin Therapeutics, Merck, Merck/Schering-Plough Partnership, Novartis, and Takeda; and is a clinical advisor with equity in Automedics Medical Systems. Dr. Wiviott has received speaking honoraria from Pfizer, Merck, AstraZeneca, and Bristol-Myers Squibb; and consulting fees from Bristol-Myers Squibb. Dr. McCabe has received grant support from Bristol-Myers Squibb (for the PROVE IT trial) and Schering-Plough. Dr. Braunwald has received grant support from Bristol-Myers Squibb (for the PROVE IT–TIMI 22 trial), Schering-Plough, and Merck; and has received honoraria and is an advisory board member of Schering-Plough and Merck.
- Received May 7, 2009.
- Revision received September 30, 2009.
- Accepted October 12, 2009.
- American College of Cardiology Foundation