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. James Shepherd, MD1,
  2. Philip Barter, MD, PHD2,
  3. Rafael Carmena, MD3,
  4. Prakash Deedwania, MD4,
  5. Jean-Charles Fruchart, PHARMD, PHD5,
  6. Steven Haffner, MD6,
  7. Judith Hsia, MD7,
  8. Andrei Breazna, PHD8,
  9. John LaRosa, MD9,
  10. Scott Grundy, MD, PHD10,
  11. David Waters, MD11 and
  12. for the Treating to New Targets Investigators
  1. 1Department of Vascular Biochemistry, University of Glasgow, Glasgow, U.K.
  2. 2The Heart Research Institute, Department of Medicine, University of Sydney, Sydney, Australia
  3. 3Endocrinology Department, Clinic University Hospital, University of Valencia, Valencia, Spain
  4. 4Cardiology Division, Veterans Affairs Central California Health Care, University of California San Francisco School of Medicine, San Francisco, California
  5. 5Lipoprotein and Atherosclerosis Research Unit, Institut National de la Santé et de la Recherche Médicale, Pasteur Institute, Lille, France
  6. 6Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
  7. 7Division of Cardiology, George Washington University Medical Center, Washington, DC
  8. 8Biometrics Department, Pfizer, New York, New York
  9. 9State University of New York Downstate Medical Center, State University of New York Health Science Center, Brooklyn, New York
  10. 10Center for Human Nutrition, Departments of Clinical Nutrition and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
  11. 11Division of Cardiology, School of Medicine, San Francisco General Hospital, University of California San Francisco School of Medicine, San Francisco, California
  1. Address correspondence and reprint requests to James Shepherd, Biochemistry, Royal Infirmary, Glasgow, G4 OSF, U.K. E-mail: jshepherd{at}gri-biochem.org.uk

Abstract

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.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 15, 2006.
    • Received December 15, 2005.
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  1. doi: 10.2337/dc05-2465 Diabetes Care June 2006 vol. 29 no. 6 1220-1226
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