Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Christopher P. Cannon, M.D., Eugene Braunwald, M.D., Carolyn H. McCabe, B.S., Daniel J. Rader, M.D., Jean L. Rouleau, M.D., Rene Belder, M.D., Steven V. Joyal, M.D., Karen A. Hill, B.A., Marc A. Pfeffer, M.D., Ph.D., Allan M. Skene, Ph.D., for the Pravastatin or Atorvastatin Evaluation and Infection TherapyThrombolysis in Myocardial Infarction 22 Investigators
Background Lipid-lowering therapy with statins reduces the riskof cardiovascular events, but the optimal level of low-densitylipoprotein (LDL) cholesterol is unclear.
Methods We enrolled 4162 patients who had been hospitalizedfor an acute coronary syndrome within the preceding 10 daysand compared 40 mg of pravastatin daily (standard therapy) with80 mg of atorvastatin daily (intensive therapy). The primaryend point was a composite of death from any cause, myocardialinfarction, documented unstable angina requiring rehospitalization,revascularization (performed at least 30 days after randomization),and stroke. The study was designed to establish the noninferiorityof pravastatin as compared with atorvastatin with respect tothe time to an end-point event. Follow-up lasted 18 to 36 months(mean, 24).
Results The median LDL cholesterol level achieved during treatmentwas 95 mg per deciliter (2.46 mmol per liter) in the standard-dosepravastatin group and 62 mg per deciliter (1.60 mmol per liter)in the high-dose atorvastatin group (P<0.001). KaplanMeierestimates of the rates of the primary end point at two yearswere 26.3 percent in the pravastatin group and 22.4 percentin the atorvastatin group, reflecting a 16 percent reductionin the hazard ratio in favor of atorvastatin (P=0.005; 95 percentconfidence interval, 5 to 26 percent). The study did not meetthe prespecified criterion for equivalence but did identifythe superiority of the more intensive regimen.
Conclusions Among patients who have recently had an acute coronarysyndrome, an intensive lipid-lowering statin regimen providesgreater protection against death or major cardiovascular eventsthan does a standard regimen. These findings indicate that suchpatients benefit from early and continued lowering of LDL cholesterolto levels substantially below current target levels.
Source Information
From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (C.P.C., E.B., C.H.M., M.A.P.); the University of Pennsylvania, Philadelphia (D.J.R.); the University of Montreal, Montreal (J.L.R.); Bristol-Myers Squibb, Princeton, N.J. (R.B., S.V.J.); and the Nottingham Clinical Research Group, Nottingham, United Kingdom (K.A.H., A.M.S.). This article was published at www.nejm.org on March 8, 2004.
Address reprint requests to Dr. Cannon at the TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, or at cpcannon{at}partners.org.
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