(Circulation. 1999;99:216-223.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Reduction of Stroke Incidence After Myocardial Infarction With Pravastatin
The Cholesterol and Recurrent Events (CARE) Study
From the Section of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH (J.F.P.); School of Public Health, University of Texas Health Science Center at Houston (B.R.D., L.A.M., L.B.P., L.M.S.); Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (F.M.S., M.A.P., E.B.); Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.); Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada (V.B.); Section of Cardiology, University of Manitoba Health Sciences Center, Winnipeg, Manitoba, Canada (T.E.C.); and Cardiology Division, University of Texas–Southwestern Medical Center at Dallas (J.R.).
Correspondence to Jonathan F. Plehn, MD, Section of Cardiology, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756. E-mail jonathan.f.plehn{at}hitchcock.org
Background—The role of lipid modification in stroke prevention is controversial, although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease.
Methods and Results—To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infarction, we followed 4159 subjects with average total and LDL serum cholesterol levels (mean, 209 and 139 mg/dL, respectively) who had sustained an infarction an average of 10 months before study entry and who were randomized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events (CARE) trial. Using prospectively defined criteria, we assessed the incidence of stroke, a prespecified secondary end point, and transient ischemic attack (TIA) over a median 5-year follow-up period. Patients were well matched for stroke risk factors and the use of antiplatelet agents (85% of subjects in each group). Compared with placebo, pravastatin lowered total serum cholesterol by 20%, LDL cholesterol by 32%, and triglycerides by 14% and raised HDL cholesterol by 5% over the course of the trial. A total of 128 strokes (52 on pravastatin, 76 on placebo) and 216 strokes or TIAs (92 on pravastatin, 124 on placebo) were observed, representing a 32% reduction (95% CI, 4% to 52%, P=0.03) in all-cause stroke and 27% reduction in stroke or TIA (95% CI, 4% to 44%, P=0.02). All categories of strokes were reduced, and treatment effect was similar when adjusted for age, sex, history of hypertension, cigarette smoking, diabetes, left ventricular ejection fraction, and baseline total, HDL, and LDL cholesterol and triglyceride levels. There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo (2 versus 6, respectively).
Conclusions—Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infarction in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy.
Key Words: stroke • cholesterol • myocardial infarction • arteriosclerosis • lipids
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P. A. Tunick and I. Kronzon Atheromas of the thoracic aorta: clinical and therapeutic update J. Am. Coll. Cardiol., March 1, 2000; 35(3): 545 - 554. [Abstract] [Full Text] [PDF]
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D. C. Hess, A. M. Demchuk, L. M. Brass, and F. M. Yatsu HMG-CoA reductase inhibitors (statins): A promising approach to stroke prevention Neurology, February 22, 2000; 54(4): 790 - 796. [Abstract] [Full Text] [PDF]
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 M. F Oliver Cholesterol and strokes BMJ, February 19, 2000; 320(7233): 459 - 460. [Full Text]
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 B. Hsiang, Y. Zhu, Z. Wang, Y. Wu, V. Sasseville, W.-P. Yang, and T. G. Kirchgessner A Novel Human Hepatic Organic Anion Transporting Polypeptide (OATP2). IDENTIFICATION OF A LIVER-SPECIFIC HUMAN ORGANIC ANION TRANSPORTING POLYPEPTIDE AND IDENTIFICATION OF RAT AND HUMAN HYDROXYMETHYLGLUTARYL-CoA REDUCTASE INHIBITOR TRANSPORTERS J. Biol. Chem., December 24, 1999; 274(52): 37161 - 37168. [Abstract] [Full Text] [PDF]
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 A. M. Demchuk, D. C. Hess, L. M. Brass, and F. M. Yatsu Is Cholesterol a Risk Factor for Stroke?: Yes Arch Neurol, December 1, 1999; 56(12): 1518 - 1520. [Full Text] [PDF]
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C. R. Kumana, B. M. Y. Cheung, and I. J. Lauder Gauging the Impact of Statins Using Number Needed to Treat JAMA, November 24, 1999; 282(20): 1899 - 1901. [Full Text] [PDF]
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E. R Mohler III, N. Delanty, D. J Rader, and E. C Raps Statins and cerebrovascular disease: plaque attack to prevent brain attack Vascular Medicine, November 1, 1999; 4(4): 269 - 272. [Abstract] [PDF]
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R. Mantyla, H. J. Aronen, O. Salonen, T. Pohjasvaara, M. Korpelainen, T. Peltonen, C.-G. Standertskjold-Nordenstam, M. Kaste, and T. Erkinjuntti Magnetic Resonance Imaging White Matter Hyperintensities and Mechanism of Ischemic Stroke Stroke, October 1, 1999; 30(10): 2053 - 2058. [Abstract] [Full Text] [PDF]
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T. K. Pfefferkorn, H.-P. Knuppel, B. R. Jaeger, J. Thiery, and G. F. Hamann Increased Cerebral CO2 Reactivity After Heparin-Mediated Extracorporal LDL Precipitation (HELP) in Patients With Coronary Heart Disease and Hyperlipidemia Stroke, September 1, 1999; 30 (9): e1802 - 1806. [Abstract] [Full Text] [PDF]
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P. A. Wolf, G. P. Clagett, J. D. Easton, L. B. Goldstein, P. B. Gorelick, M. Kelly-Hayes, R. L. Sacco, and J. P. Whisnant Preventing Ischemic Stroke in Patients With Prior Stroke and Transient Ischemic Attack : A Statement for Healthcare Professionals From the Stroke Council of the American Heart Association Stroke, September 1, 1999; 30(9): 1991 - 1994. [Full Text] [PDF]
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F. B. Hu, M. J. Stampfer, E. B. Rimm, J. E. Manson, A. Ascherio, G. A. Colditz, B. A. Rosner, D. Spiegelman, F. E. Speizer, F. M. Sacks, et al. A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women JAMA, April 21, 1999; 281(15): 1387 - 1394. [Abstract] [Full Text] [PDF]
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 Pravastatin Reduces Stroke Too Journal Watch Cardiology, March 12, 1999; 1999(312): 1 - 1. [Full Text]
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 Reduction of Stroke Incidence with Pravastatin Journal Watch (General), February 2, 1999; 1999(202): 3 - 3. [Full Text]
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