Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
John C. LaRosa, M.D., Scott M. Grundy, M.D., Ph.D., David D. Waters, M.D., Charles Shear, Ph.D., Philip Barter, M.D., Ph.D., Jean-Charles Fruchart, Pharm.D., Ph.D., Antonio M. Gotto, M.D., D.Phil., Heiner Greten, M.D., John J.P. Kastelein, M.D., James Shepherd, M.D., Nanette K. Wenger, M.D., for the Treating to New Targets (TNT) Investigators
Background Previous trials have demonstrated that lowering low-densitylipoprotein (LDL) cholesterol levels below currently recommendedlevels is beneficial in patients with acute coronary syndromes.We prospectively assessed the efficacy and safety of loweringLDL cholesterol levels below 100 mg per deciliter (2.6 mmolper liter) in patients with stable coronary heart disease (CHD).
Methods A total of 10,001 patients with clinically evident CHDand LDL cholesterol levels of less than 130 mg per deciliter(3.4 mmol per liter) were randomly assigned to double-blindtherapy and received either 10 mg or 80 mg of atorvastatin perday. Patients were followed for a median of 4.9 years. The primaryend point was the occurrence of a first major cardiovascularevent, defined as death from CHD, nonfatal nonprocedure-relatedmyocardial infarction, resuscitation after cardiac arrest, orfatal or nonfatal stroke.
Results The mean LDL cholesterol levels were 77 mg per deciliter(2.0 mmol per liter) during treatment with 80 mg of atorvastatinand 101 mg per deciliter (2.6 mmol per liter) during treatmentwith 10 mg of atorvastatin. The incidence of persistent elevationsin liver aminotransferase levels was 0.2 percent in the groupgiven 10 mg of atorvastatin and 1.2 percent in the group given80 mg of atorvastatin (P<0.001). A primary event occurredin 434 patients (8.7 percent) receiving 80 mg of atorvastatin,as compared with 548 patients (10.9 percent) receiving 10 mgof atorvastatin, representing an absolute reduction in the rateof major cardiovascular events of 2.2 percent and a 22 percentrelative reduction in risk (hazard ratio, 0.78; 95 percent confidenceinterval, 0.69 to 0.89; P<0.001). There was no differencebetween the two treatment groups in overall mortality.
Conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatinper day in patients with stable CHD provides significant clinicalbenefit beyond that afforded by treatment with 10 mg of atorvastatinper day. This occurred with a greater incidence of elevatedaminotransferase levels.
Source Information
From the State University of New York Health Science Center, Brooklyn (J.C.L.); the University of Texas Southwestern Medical Center, Dallas (S.M.G.); San Francisco General Hospital, San Francisco (D.D.W.); Pfizer, Groton, Conn. (C.S.); the Heart Research Institute, Sydney (P.B.); Institut Pasteur, Lille, France (J.-C.F.); Weill Medical College of Cornell University, New York (A.M.G.); Universitätsklinikum Eppendorf, Hamburg, Germany (H.G.); Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.); the University of Glasgow, Glasgow, United Kingdom (J.S.); and Emory University School of Medicine, Atlanta (N.K.W.). This article was published at www.nejm.org on March 8, 2005.
Address reprint requests to Dr. LaRosa at the State University of New York Health Science Center, 450 Clarkson Ave., Brooklyn, NY 11203, or at jclarosa{at}downstate.edu.
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