Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of stroke.
OBJECTIVE
To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease.


METHODS
Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials.


RESULTS
Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome.


CONCLUSIONS
The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.
Warshafsky
S
S
Section of General Internal Medicine, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Packard
D
D
Marks
S J
SJ
Sachdeva
N
N
Terashita
D M
DM
Kaufman
G
G
Sang
K
K
Deluca
A J
AJ
Peterson
S J
SJ
Frishman
W H
WH
D000368:Aged; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D020521:Stroke / Q000401:mortality* / Q000517:prevention & control*; D016019:Survival Analysis; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors