Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Abstract

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.