Effect of statins on venous thromboembolic events: A meta-analysis of published and unpublished evidence from randomised controlled trials

Background: It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins. Methods: We searched MEDLINE, EMBASE and the Cochrane's CENTRAL up to October 2010 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events. Findings: Twenty one trials of statin versus control (105 627 participants) and seven trials of an intensive versus a standard dose statin regimen (40 594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (464 statin vs 520 control, odds ratio [OR]=0.89, 95% confidence interval [CI] 0.78 to 1.01, p=0.07) with no evidence of heterogeneity between effects on deep vein thrombosis (266 vs 310, OR 0.86, 99% CI 0.69-1.07) and effects on pulmonary embolism (204 vs 222, OR 0.92, 99% CI 0.71-1.19). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (430 vs 460, OR=0.93 [95% CI 0.82-1.07], p=0.32 among the other 20 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 vs 202, OR=0.98, 95% CI 0.80 to 1.20, p=0.87). Conclusions: The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more modest reduction in venous thromboembolic events cannot be ruled out