Impact of Statins on Risk of Stroke: A Meta-Analysis

Nickole N Henyan, PharmD; Daniel M Riche, PharmD BCPS; Honey E East, MD; Pamela N Gann, PharmD

Disclosures

The Annals of Pharmacotherapy. 2007;41(12):1937-1945. 

In This Article

Results

Study Characteristics

A total of 56 full-text reports of trials and 3 abstracts were identified and retrieved. Upon review and evaluation, 27 trials (and 1 contributory abstract) met all of the inclusion criteria ( Table 1 ).[5,6,7,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45] The majority of patients were white males with a history of hyperlipidemia. Most studies were a mixture of primary and secondary cardiovascular disease prevention trials with a placebo run-in period. Approximately 21% of the overall population were current smokers.

All Cerebrovascular Events

A total of 26 trials (N = 100,560) reported data on all CVEs.[5,6,7,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44] Upon meta-analysis, statin therapy significantly reduced the risk of all CVEs (RR 0.83; 95% CI 0.76 to 0.91; Figure 2). Statistical heterogeneity was not observed among the trials (Q statistic; p = 0.19). Publication bias was not evident via Egger weighted regression (p = 0.35).

Figure 2.

All cerebrovascular events incidence. Relative risk meta-analysis plot (random effects).

Ischemic Stroke

Six trials (n = 37,292) were included in the analysis of the effect of statin therapy on ischemic stroke.[6,23,24,25,44,45] Upon meta-analysis, statin therapy was shown to significantly reduce the risk of ischemic stroke (RR 0.79; 95% CI 0.63 to 0.99; Figure 3). Significant statistical heterogeneity was observed among trials (Q statistic; p = 0.0229). Publication bias was not evident via Egger weighted regression (p = 0.9848).

Figure 3.

Ischemic stroke incidence. Relative risk meta-analysis plot (random effects).

Hemorrhagic Stroke

Nine trials (n = 57,895) reported data on hemorrhagic stroke.[5,6,7,23,24,25,26,27,44] Upon meta-analysis, statin therapy was shown to nonsignificantly increase the risk of hemorrhagic stroke (RR 1.11; 95% CI 0.77 to 1.60; Figure 4). Statistical heterogeneity was not observed among the trials (Q statistic; p = 0.15). Publication bias was not evident via Egger weighted regression (p = 0.24).

Figure 4.

Hemorrhagic stroke incidence. Relative risk meta-analysis plot (random effects).

Sensitivity Analysis

The results of our meta-analysis were not altered via methodological changes. Use of a fixed-effects model (Mantel-Haenszel, Rothman-Boice) did not alter the statistical significance of reduced risk for all CVEs (RR 0.82; 95% CI 0.77 to 0.88) or ischemic stroke (RR 0.76; 95% CI 0.69 to 0.84) or the nonsignificance of increased risk of hemorrhagic stroke (RR 1.15; 95% CI 0.90 to 1.45).

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