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(Stroke. 1997;28:946-950.)
© 1997 American Heart Association, Inc.


Articles

Stroke, Statins, and Cholesterol

A Meta-Analysis of Randomized, Placebo-Controlled, Double-Blind Trials With HMG-CoA Reductase Inhibitors

Gerard J. Blauw, MD, PhD; A. Margot Lagaay, MD, PhD; Augustinus H. M. Smelt, MD, PhD; Rudi G. J. Westendorp, MD, PhD

From the Departments of General Internal Medicine and Clinical Epidemiology (R.G.J.W.), Leiden (Netherlands) University Medical Centre.

Correspondence to Dr G.J. Blauw, MD, PhD, Department of General Internal Medicine, Section of Gerontology and Geriatrics, C1-R41, Leiden University Medical Centre, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, Netherlands.

Background and Purpose To estimate the effect of 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors ("statins") on stroke risk, we combined the data of the randomized, placebo-controlled, double-blind trials with HMG-CoA reductase inhibitors published so far.

Methods The studies were identified using the Medline CD+ and Current Contents databases from January 1980 through May 1996, inclusive. All studies were evaluated on the use of a placebo control, monotherapy, and double blindness. When the type of stroke or the occurrence of clinical events or adverse effects were incompletely or not reported, the investigators were contacted personally. For each trial, the number of strokes in the treatment arm was compared with the number of strokes expected on all observations under the assumption that drug treatment had no effect.

Results A total of 462 strokes among 20 438 participants in 13 trials could be analyzed. A total of 181 strokes were observed in patients randomized to treatment with an HMG-CoA reductase inhibitor and 261 strokes in patients randomized to placebo. A lower than expected number of strokes was observed in the treatment groups of all but one trial (P=.001). Treatment with an HMG-CoA reductase inhibitor led to an overall risk reduction of 31% (odds ratio, 0.69; 95% confidence interval, 0.57 to 0.83).

Conclusions The combined data suggest that treatment with HMG-CoA reductase inhibitors prevents stroke in middle-aged persons. Because stroke is especially common in older age, these data reinforce the need for clinical trials to evaluate the effect of HMG-CoA reductase inhibitors in preventing stroke in the elderly.


Key Words: cholesterol • HMG-CoA reductase inhibitors • meta-analysis • stroke prevention




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