Effects of statins on stroke prevention in patients with and without coronary heart disease: A meta-analysis of randomized controlled trials

https://doi.org/10.1016/j.amjmed.2004.04.022Get rights and content

Purpose

To assess if lipid-lowering interventions (statins, fibrates, resins, n-3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and without coronary heart disease.

Methods

We systematically searched the literature up to August 2002 to retrieve all randomized controlled trials of lipid-lowering interventions that reported nonfatal and fatal stroke and mortality data. The search yielded 65 trials with 200,607 patients for a meta-analysis to determine whether treatment effects differed between types of lipid-lowering interventions and between patient samples with and without coronary heart disease.

Results

The risk ratio for nonfatal and fatal stroke for statins as compared with control interventions was 0.82 (95% confidence interval [CI]: 0.76 to 0.90). The corresponding risk ratios for statins as compared with control were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and 0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The confidence intervals of risk ratios for nonfatal and fatal stroke associated with fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence intervals for these interventions in patients with and without coronary heart disease. Weighted meta-regression analysis suggested a stronger association of stroke reduction with statin treatment than with the extent of cholesterol reduction.

Conclusion

This meta-analysis suggests that statins reduce the incidence of stroke in patients with and without coronary heart disease.

Section snippets

Methods

MEDLINE, EMBASE, Pascal, Index Medicus, and the Cochrane Library were searched without language restrictions to identify all randomized controlled trials published through August 2002 that compared dietary or pharmaceutical lipid-lowering interventions with placebo or usual diet. We also searched previously published meta-analyses and reference lists of identified publications for citations of additional relevant articles up to June 2003. The original study investigators were contacted for

Results

We identified 120 randomized controlled trials that tested lipid-lowering interventions and reported mortality data. Clinical outcomes of four completed trials are not yet published (86, 87, 88, 89). Of the remaining 116 trials, 69 provided data on the incidence of nonfatal and fatal stroke and had a minimum follow-up of 6 months. Four trials were excluded because they were restricted to patients who had previous strokes (13, 14), received hormone therapy (15), or undergone ileal bypass surgery

Discussion

This systematic review suggests that statins may reduce fatal and nonfatal strokes in hyperlipidemic patients with or without pre-existing coronary heart disease. The number needed to treat to prevent one stroke per year with statins is 617 in patients with established coronary heart disease (based on an annual stroke risk of 0.9%) and 2778 in those without established coronary heart disease (based on an annual stroke risk of 0.2%). These effects are moderate but statistically significant,

Acknowledgment

We would like to thank P. Wolf for performing the literature search, C. Schindler for statistical advice, and the authors who contributed unpublished data from their trials.

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