title: 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.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiology, San Francisco General Hospital, and the University of California, San Francisco School of Medicine, San Francisco, Calif 94110, USA. dwaters@medsfgh.ucsf.edu
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Schwartz
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Zeiher
authors.forename: Michael F
authors.initials: MF
authors.lastname: Oliver
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.forename: Michael
authors.initials: M
authors.lastname: Ezekowitz
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Chaitman
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Leslie
authors.forename: Theresa
authors.initials: T
authors.lastname: Stern
mesh_terms: D000208:Acute Disease; D000368:Aged; D000789:Angina, Unstable / Q000150:complications / Q000188:drug therapy*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D008055:Lipids / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy*; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use*; D012306:Risk; D018570:Risk Assessment; D055502:Secondary Prevention; D020521:Stroke / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin