Harvey D. White, D.Sc., R. John Simes, M.D., Neil E. Anderson, M.B., Graeme J. Hankey, M.D., John D.G. Watson, M.D., David Hunt, M.D., David M. Colquhoun, M.D., Paul Glasziou, M.D., Stephen MacMahon, Ph.D., M.P.H., Adrienne C. Kirby, M.Sc., Malcolm J. West, M.B., Ph.D., and Andrew M. Tonkin, M.D.
Background Several epidemiologic studies have concluded thatthere is no relation between total cholesterol levels and therisk of stroke. In some studies that classified strokes accordingto cause, there was an association between increasing cholesterollevels and the risk of ischemic stroke and a possible associationbetween low cholesterol levels and the risk of hemorrhagic stroke.Recent reviews of trials of 3-hydroxy-3-methylglutaryl–coenzymeA reductase inhibitors have suggested that these agents mayreduce the risk of stroke.
Methods In a double-blind trial (the Long-Term Interventionwith Pravastatin in Ischaemic Disease study), we compared theeffects of pravastatin on mortality due to coronary heart disease(the primary end point) with the effects of placebo among 9014patients with a history of myocardial infarction or unstableangina and a total cholesterol level of 155 to 271 mg per deciliter(4.0 to 7.0 mmol per liter). Our goal in the present study wasto assess effects on stroke from any cause and nonhemorrhagicstroke, which were secondary end points.
Results There were 419 strokes among 373 patients over a follow-upperiod of six years. A total of 309 strokes were classifiedas ischemic, 31 as hemorrhagic, and 79 as of unknown type. Amongthe patients given placebo, the risk of stroke was 4.5 percent,as compared with 3.7 percent among those given pravastatin (relativereduction in risk, 19 percent; 95 percent confidence interval,0 to 34 percent; P=0.05). Nonhemorrhagic stroke occurred in4.4 percent of the patients given placebo, as compared with3.4 percent of those given pravastatin (reduction in risk, 23percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence,0.2 percent in the placebo group vs. 0.4 percent in the pravastatingroup; P=0.28).
Conclusions Pravastatin has a moderate effect in reducing therisk of stroke from any cause and the risk of nonhemorrhagicstroke in patients with previous myocardial infarction or unstableangina.
Source Information
From the Cardiology Department, Green Lane Hospital (H.D.W.), and the Department of Medicine, University of Auckland (N.E.A.) — both in Auckland, New Zealand; and the National Health and Medical Research Council Clinical Trials Centre (R.J.S., A.C.K.), the Department of Medicine (J.D.G.W.), and the Institute for International Health Research and Development (S.M.), University of Sydney, Sydney; the Stroke Unit, Royal Perth Hospital, Perth (G.J.H.); the Cardiac Department, Royal Melbourne Hospital (D.H.), Melbourne; the Wesley Medical Centre (D.M.C.), the Department of Social and Preventive Medicine, Mayne Medical School (P.G.), and the Department of Medicine (M.J.W.), University of Queensland, Brisbane; and the National Heart Foundation of Australia, Melbourne (A.M.T.) — all in Australia.
Address reprint requests to Dr. White at the Cardiology Department, Green Lane Hospital, Private Bag 92 189, Auckland 1030, New Zealand, or at harveyw{at}ahsl.co.nz.
Pravastatin Therapy and the Risk of Stroke
Brett A. S., Meilof J. F., Uitdehaag B. M.I., Fruchter O., White H. D., Simes R. J., Tonkin A. M., The LIPID Study Group
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N Engl J Med 2000;
343:1894-1896, Dec 21, 2000.
Correspondence
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