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.
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.
Waters
David D
DD
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
Schwartz
Gregory G
GG
Olsson
Anders G
AG
Zeiher
Andreas
A
Oliver
Michael F
MF
Ganz
Peter
P
Ezekowitz
Michael
M
Chaitman
Bernard R
BR
Leslie
Sally J
SJ
Stern
Theresa
T
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
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin