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Effect of Lowering LDL Cholesterol Substantially Below Currently Recommended Levels in Patients With Coronary Heart Disease and Diabetes

The Treating to New Targets (TNT) study

¹ Department of Vascular Biochemistry, University of Glasgow, Glasgow, U.K.
² The Heart Research Institute, Department of Medicine, University of Sydney, Sydney, Australia
³ Endocrinology Department, Clinic University Hospital, University of Valencia, Valencia, Spain
⁴ Cardiology Division, Veterans Affairs Central California Health Care, University of California San Francisco School of Medicine, San Francisco, California
⁵ Lipoprotein and Atherosclerosis Research Unit, Institut National de la Santé et de la Recherche Médicale, Pasteur Institute, Lille, France
⁶ Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
⁷ Division of Cardiology, George Washington University Medical Center, Washington, DC
⁸ Biometrics Department, Pfizer, New York, New York
⁹ State University of New York Downstate Medical Center, State University of New York Health Science Center, Brooklyn, New York
¹⁰ Center for Human Nutrition, Departments of Clinical Nutrition and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
¹¹ Division of Cardiology, School of Medicine, San Francisco General Hospital, University of California San Francisco School of Medicine, San Francisco, California

Address correspondence and reprint requests to James Shepherd, Biochemistry, Royal Infirmary, Glasgow, G4 OSF, U.K. E-mail: jshepherd{at}gri-biochem.org.uk

OBJECTIVE—The Treating to New Targets study showed that intensive lipid-lowering therapy with atorvastatin 80 mg/day provides significant clinical benefit beyond that afforded by atorvastatin 10 mg/day in patients with stable coronary heart disease (CHD). The objective of our study was to investigate whether similar benefits of high-dose intensive atorvastatin therapy can be achieved in patients with CHD and diabetes.

RESEARCH DESIGN AND METHODS—A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke.

RESULTS—End-of-treatment mean LDL cholesterol levels were 98.6 mg/dl with atorvastatin 10 mg and 77.0 mg/dl with atorvastatin 80 mg. A primary event occurred in 135 patients (17.9%) receiving atorvastatin 10 mg, compared with 103 patients (13.8%) receiving atorvastatin 80 mg (hazard ratio 0.75 [95% CI 0.58–0.97], P = 0.026). Significant differences between the groups in favor of atorvastatin 80 mg were also observed for time to cerebrovascular event (0.69 [0.48–0.98], P = 0.037) and any cardiovascular event (0.85 [0.73–1.00], P = 0.044). There were no significant differences between the treatment groups in the rates of treatment-related adverse events and persistent elevations in liver enzymes.

CONCLUSIONS—Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.

Abbreviations: ADA, American Diabetes Association • CHD, coronary heart disease • TNT, Treating to New Targets

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