Volume 335Number 14?1001The New EnglandJournal ofMedicine Copyright, 1996, by the Massachusetts Medical SocietyVOLUME 335OCTOBER3, 1996NUMBER 14THE EFFECT OF PRAVASTATIN ON CORONARY EVENTS AFTER MYOCARDIAL INFARCTION IN PATIENTS WITH AVERAGE CHOLESTEROL LEVELSFRANKM. SACKS, M.D., MARCA. PFEFFER, M.D., PH.D., LEMUELA. MOYE, M.D., PH.D., JEANL. ROULEAU, M.D., JOHND. RUTHERFORD, M.D., THOMASG. COLE, PH.D., LISABROWN, M.P.H., J. WAYNEWARNICA, M.D., J. MALCOLMO. ARNOLD, M.D., CHUAN-CHUANWUN, PH.D., BARRYR. DAVIS, M.D., PH.D.,ANDEUGENEBRAUNWALD, M.D., FORTHECHOLESTEROLANDRECURRENTEVENTSTRIALINVESTIGATORS*ABSTRACTBackgroundIn patients with high cholesterol lev- els, lowering the cholesterol level reduces the risk of coronary events, but the effect of lowering cholester- ol levels in the majority of patients with coronary disease, who have average levels, is less clear.MethodsIn a double-blind trial lasting five years, we administered either 40 mg of pravastatin per day or placebo to 4159 patients (3583 men and 576 wom- en) with myocardial infarction who had plasma total cholesterol levels below 240 mg per deciliter (mean, 209) and low-density lipoprotein (LDL) cholesterol levels of 115 to 174 mg per deciliter (mean, 139). The primary end point was a fatal coronary event or a nonfatal myocardial infarction.ResultsThe frequency of the primary end point was 10.2 percent in the pravastatin group and 13.2 percent in the placebo group, an absolute difference of 3 percentage points and a 24 percent reduction in risk (95 percent confidence interval, 9 to 36 percent; P?0.003). Coronary bypass surgery was needed in 7.5 percent of the patients in the pravastatin group and 10 percent of those in the placebo group, a 26 percent reduction (P?0.005), and coronary angio- plasty was needed in 8.3 percent of the pravastatin group and 10.5 percent of the placebo group, a 23 percent reduction (P?0.01). The frequency of stroke was reduced by 31 percent (P?0.03). There were no significant differences in overall mortality or mortal- ity from noncardiovascular causes. Pravastatin low- ered the rate of coronary events more among wom- en than among men. The reduction in coronary events was also greater in patients with higher pretreat- ment levels of LDL cholesterol.ConclusionsThese results demonstrate that the benefit of cholesterol-lowering therapy extends to the majority of patients with coronary disease who have average cholesterol levels. (N Engl J Med 1996; 335:1001-9.)1996, Massachusetts Medical Society.From the Departments of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston (F.M.S., M.A.P ., L.B., E.B.); the Univer- sity of Texas School of Public Health, Houston (L.A.M., C.-C.W., B.R.D.); the University of Sherbrooke, Sherbrooke, Que., Canada (J.L.R.); the Uni- versity of Texas Southwestern Medical Center, Dallas (J.D.R.); Washington University, St. Louis (T.G.C.); Foothills Hospital, Calgary, Alta., Canada (J.W.W.); and Victoria Hospital, London, Ont., Canada (J.M.O.A.). Address reprint requests to Dr. Sacks at Brigham and Womens Hospital, 75 Francis St., Boston, MA 02115. Other contributing authors were Pierre Theroux, M.D., Montreal Heart Institute, Montreal; David T. Nash, M.D., State University of New York Health Sciences Center, Syracuse; and C. Morton Hawkins, D.Sc., Univer- sity of Texas School of Public Health, Houston.*Participants in the Cholesterol and Recurrent Events trial are listed in the Appendix.HE plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol are important risk factors for coronary heart disease.1-4However, the relation between plasma cholesterol and coronary events appears to be stronger if levels are at elevated, rather than average, values.1-4Angiography in clinical trials has demon- strated that lowering cholesterol levels slows the pro- gression and promotes the regression of coronary ath- erosclerosis.5These beneficial changes are also directly related to the pretreatment level of LDL cholester- ol,5,6with little benefit occurring in patients with av- erage base-line levels.7Clinical trials have shown that lowering elevated LDL cholesterol levels prevents both first and recurrent coronary events.8-11However, it has not been clear whether coronary events can be prevented by cholesterol-lowering therapy in patients who do not have hypercholesterolemia. This issue is of importance because the large majority of patients with coronary disease have cholesterol levels that are, like those of the general population,12in the average, not the elevated, range.13-16The Cholesterol and Recurrent Events (CARE)TDownloaded from www.nejm.org on November 27, 2008 . Copyright 1996 Massachusetts Medical Society. All rights reserved. 1002?October 3, 1996The New England Journal of Medicinetrial and its entry criteria (a plasma total cholesterol level of less than 240 mg per deciliter 6.2 mmol per liter and an LDL cholesterol level of 115 to 174 mg per decilit