(Circulation. 1998;98:2513-2519.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Cardiovascular Events and Their Reduction With Pravastatin in Diabetic and Glucose-Intolerant Myocardial Infarction Survivors With Average Cholesterol Levels
Subgroup Analyses in the Cholesterol And Recurrent Events (CARE) Trial
From the University of Miami School of Medicine, Miami, Fla (R.B.G.); the University of Texas School of Public Health, Houston, Tex (L.A.M., B.R.D.); Bristol Myers Squibb, Princeton, NJ (M.J.M.); Medlantic Research Institute, Washington, DC (B.V.H.); Washington Hospital Center, Washington, DC (W.J.H.); Washington University, St. Louis, Mo (T.G.C.); and Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (F.M.S., M.A.P., E.B.).
Correspondence to Frank M. Sacks, MD, Nutrition Department, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu
Background—Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether lipid-lowering treatment with pravastatin prevents recurrent cardiovascular events in diabetic patients with CHD and average cholesterol levels.
Methods and Results—The Cholesterol And Recurrent Events (CARE) trial, a 5-year trial that compared the effect of pravastatin and placebo, included 586 patients (14.1%) with clinical diagnoses of diabetes. The participants with diabetes were older, more obese, and more hypertensive. The mean baseline lipid concentrations in the group with diabetes—136 mg/dL LDL cholesterol, 38 mg/dL HDL cholesterol, and 164 mg/dL triglycerides—were similar to those in the nondiabetic group. LDL cholesterol reduction by pravastatin was similar (27% and 28%) in the diabetic and nondiabetic groups, respectively. In the placebo group, the diabetic patients suffered more recurrent coronary events (CHD death, nonfatal myocardial infarction [MI], CABG, and PTCA) than did the nondiabetic patients (37% versus 25%). Pravastatin treatment reduced the absolute risk of coronary events for the diabetic and nondiabetic patients by 8.1% and 5.2% and the relative risk by 25% (P=0.05) and 23% (P<0.001), respectively. Pravastatin reduced the relative risk for revascularization procedures by 32% (P=0.04) in the diabetic patients. In the 3553 patients who were not diagnosed as diabetic, 342 had impaired fasting glucose at entry defined by the American Diabetes Association as 110 to 125 mg/dL. These nondiabetic patients with impaired fasting glucose had a higher rate of recurrent coronary events than those with normal fasting glucose (eg, 13% versus 10% for nonfatal MI). Recurrence rates tended to be lower in the pravastatin compared with placebo group (eg, –50%, P=0.05 for nonfatal MI).
Conclusions—Diabetic patients and nondiabetic patients with impaired fasting glucose are at high risk of recurrent coronary events that can be substantially reduced by pravastatin treatment.
Key Words: diabetes mellitus • coronary disease • glucose • lipoproteins
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M. F. Saad, S. Greco, K. Osei, A. J. Lewin, C. Edwards, M. Nunez, and R. R. Reinhardt Ragaglitazar Improves Glycemic Control and Lipid Profile in Type 2 Diabetic Subjects: A 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm Diabetes Care, June 1, 2004; 27(6): 1324 - 1329. [Abstract] [Full Text] [PDF]
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R. M. Krauss Lipids and Lipoproteins in Patients With Type 2 Diabetes Diabetes Care, June 1, 2004; 27(6): 1496 - 1504. [Abstract] [Full Text] [PDF]
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M D Feher Diabetes: preventing coronary heart disease in a high risk group Heart, June 1, 2004; 90(suppl_4): iv18 - iv21. [Abstract] [Full Text] [PDF]
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R. W. Grant, P. A. Pirraglia, J. B. Meigs, and D. E. Singer Trends in Complexity of Diabetes Care in the United States From 1991 to 2000 Arch Intern Med, May 24, 2004; 164(10): 1134 - 1139. [Abstract] [Full Text] [PDF]
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G. F Watts Treating low HDL-cholesterol in normocholesterolaemic patients with coronary disease: statins, fibrates or horses for courses? Eur. Heart J., May 1, 2004; 25(9): 716 - 719. [Full Text] [PDF]
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M. F. Lopes-Virella, M. Mironova, E. Stephan, R. Durazo-Arvizu, and G. Virella Role of Simvastatin as an Immunomodulator in Type 2 Diabetes Diabetes Care, April 1, 2004; 27(4): 908 - 913. [Abstract] [Full Text] [PDF]
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D. W. Sommeijer, M. R. MacGillavry, J. C.M. Meijers, A. P. Van Zanten, P. H. Reitsma, and H. T. Cate Anti-Inflammatory and Anticoagulant Effects of Pravastatin in Patients With Type 2 Diabetes Diabetes Care, February 1, 2004; 27(2): 468 - 473. [Abstract] [Full Text] [PDF]
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M. Hanefeld, M. Cagatay, T. Petrowitsch, D. Neuser, D. Petzinna, and M. Rupp Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies Eur. Heart J., January 1, 2004; 25(1): 10 - 16. [Abstract] [Full Text] [PDF]
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B. K. Skrumsager, K. K. Nielsen, M. Muller, G. Pabst, P. G. Drake, and B. Edsberg Ragaglitazar: The Pharmacokinetics, Pharmacodynamics, and Tolerability of a Novel Dual PPAR{alpha} and {gamma} Agonist in Healthy Subjects and Patients with Type 2 Diabetes J. Clin. Pharmacol., November 1, 2003; 43(11): 1244 - 1256. [Abstract] [Full Text] [PDF]
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R. B. Goldberg Statin Treatment in Diabetic Subjects: What the Heart Protection Study Shows Clin. Diabetes, October 1, 2003; 21(4): 151 - 152. [Full Text] [PDF]
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A. Keech, D. Colquhoun, J. Best, A. Kirby, R. J. Simes, D. Hunt, W. Hague, E. Beller, M. Arulchelvam, J. Baker, et al. Secondary Prevention of Cardiovascular Events With Long-Term Pravastatin in Patients With Diabetes or Impaired Fasting Glucose: Results from the LIPID trial Diabetes Care, October 1, 2003; 26(10): 2713 - 2721. [Abstract] [Full Text] [PDF]
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T. F. Luscher, M. A. Creager, J. A. Beckman, and F. Cosentino Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part II Circulation, September 30, 2003; 108(13): 1655 - 1661. [Full Text] [PDF]
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Y. Young-Xu, K. A. Chan, J. K. Liao, S. Ravid, and C. M. Blatt Long-term statin use and psychological well-being J. Am. Coll. Cardiol., August 20, 2003; 42(4): 690 - 697. [Abstract] [Full Text] [PDF]
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C. Glumer, T. Jorgensen, and K. Borch-Johnsen Prevalences of Diabetes and Impaired Glucose Regulation in a Danish Population: The Inter99 study Diabetes Care, August 1, 2003; 26(8): 2335 - 2340. [Abstract] [Full Text] [PDF]
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C. Torp-Pedersen, C. Rask-Madsen, I. Gustafsson, F. Gustafsson, and L. Kober Diabetes mellitus and cardiovascular risk: just another risk factor? Eur. Heart J. Suppl., August 1, 2003; 5(suppl_F): F26 - F32. [Abstract] [PDF]
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A. M. Wagner, O. Jorba, R. Bonet, J. Ordonez-Llanos, and A. Perez Efficacy of Atorvastatin and Gemfibrozil, Alone and in Low Dose Combination, in the Treatment of Diabetic Dyslipidemia J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3212 - 3217. [Abstract] [Full Text] [PDF]
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 K. E. Friday Aggressive Lipid Management for Cardiovascular Prevention: Evidence from Clinical Trials Experimental Biology and Medicine, July 1, 2003; 228(7): 769 - 778. [Abstract] [Full Text] [PDF]
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F. B. Hu and J. E. Manson Walking: The Best Medicine for Diabetes? Arch Intern Med, June 23, 2003; 163(12): 1397 - 1398. [Full Text] [PDF]
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G. Reaven Type 2 Diabetes and Coronary Heart Disease: We Keep Learning How Little We Know Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 917 - 918. [Full Text] [PDF]
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M. Brandle, M. B. Davidson, D. L. Schriger, B. Lorber, and W. H. Herman Cost Effectiveness of Statin Therapy for the Primary Prevention of Major Coronary Events in Individuals With Type 2 Diabetes Diabetes Care, June 1, 2003; 26(6): 1796 - 1801. [Abstract] [Full Text] [PDF]
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K. J. Craig, K. Donovan, M. Munnery, D. R. Owens, J. D. Williams, and A. O. Phillips Identification and Management of Diabetic Nephropathy in the Diabetes Clinic Diabetes Care, June 1, 2003; 26(6): 1806 - 1811. [Abstract] [Full Text] [PDF]
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G. Steiner DAIS: how it relates to other lipid intervention studies in diabetes The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 212 - 215. [Abstract] [PDF]
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P. Durrington Clinical trials of lipid-lowering medication in diabetes The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 217 - 220. [Abstract] [PDF]
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