Published online before print September 3, 2002, doi: 10.1161/01.CIR.0000031568.40630.1C
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(Circulation. 2002;106:1690.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of Atorvastatin on Stroke in Patients With Unstable Angina or Non-Q-Wave Myocardial Infarction
A Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Substudy
From the Division of Cardiology, San Francisco General Hospital, and the University of California, San Francisco School of Medicine, San Francisco, Calif (D.D.W.); the Cardiology Division, Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, Co (G.G.S.); the Faculty of Health Sciences, University of Linköping, Linköping, Sweden (A.G.O.); the Cardiology Department, Wolfgang Johannes Goethe University, Frankfurt, Germany (A.Z.); the Department of Cardiac Medicine, National Heart and Lung Institute, Imperial College, London, UK (M.F.O.); the Cardiovascular Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (P.G.); Medical College of Pennsylvania, Hahnemann University, Philadelphia, Pa (M.E.); the Division of Cardiology, St Louis University School of Medicine, St Louis, Mo (B.R.C.); Pfizer Pharmaceuticals Group, New York, NY (S.J.L.); and Pfizer Global Research and Development, Ann Arbor, Mich (T.S.).
Correspondence to David D. Waters, MD, Division of Cardiology, Room 5G1, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110. E-mail dwaters{at}medsfgh.ucsf.edu
Background— This report describes the effect of intensive cholesterol lowering with atorvastatin on the incidence of nonfatal stroke, a secondary end point, in a randomized, placebo-controlled trial of patients with unstable angina or non-Q-wave myocardial infarction. The primary end point, a composite of death, nonfatal myocardial infarction, resuscitated cardiac arrest, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization, was reduced from 17.4% in the placebo group to 14.8% in the atorvastatin group over the 16 weeks of the trial (P=0.048).
Methods and Results— Strokes were adjudicated by a blinded end-point committee using standard clinical and imaging criteria. The outcomes of nonfatal stroke and fatal plus nonfatal stroke were analyzed by time to first occurrence during the 16-week trial. Of 38 events (in 36 patients) adjudicated as fatal or nonfatal strokes, 3 were classified as hemorrhagic, one as embolic, and 29 as thrombotic or embolic; 5 could not be categorized. Nonfatal stroke occurred in 9 patients in the atorvastatin group and 22 in the placebo group (relative risk, 0.40; 95% confidence intervals, 0.19 to 0.88; P=0.02). Fatal or nonfatal stroke occurred in 12 atorvastatin patients and 24 placebo patients (relative risk, 0.49; 95% confidence intervals, 0.24 to 0.98; P=0.04). All 3 hemorrhagic strokes occurred in the placebo group.
Conclusion— Intensive cholesterol lowering with atorvastatin over 16 weeks in patients with acute coronary syndromes reduced the overall stroke rate by half and did not cause hemorrhagic stroke. These findings need to be confirmed in future trials.
Key Words: cholesterol • stroke • angina • myocardial infarction • statins
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Circulation 2002 106: 1595-1598.
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