High-dose statin therapy and risk of intracerebral hemorrhage: a meta-analysis

Abstract

Statin plays a major role in the primary and secondary prevention of cardiovascular disease (CVD). Inconsistent findings in the studies have been observed toward the risk of intracerebral hemorrhage (ICH) using higher dose of statin. To examine this issue, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the association between higher dose of various statins and risk of ICH among patients with CVD. Literature was searched for studies published before June 10, 2015, using electronic database 'PubMed', 'EMBASE', and 'Google Scholar' as well as from many trial databases. The following search terms were used: 'Statin therapy' AND 'Cardiovascular Disease', AND 'Dose' AND 'Intracerebral hemorrhage', AND 'Randomized Controlled Trials' AND 'High Dose Statin'. High dose of statins was defined as atorvastatin 80 mg, simvastatin 80 mg, pravastatin 40 mg, rosuvastatin 20 mg per day. Fixed-effect model was used to estimate the risk ratio (RR) and 95% confidence interval (CI) if heterogeneity was <50%; otherwise, random-effect model was used. Begg's funnel plot was used to assess the publication bias. Seven RCTs involving 31,099 subjects receiving high-dose statin and 31,105 subjects receiving placebo were analyzed in our meta-analysis. A significant risk of ICH was observed in subjects with higher dose of statin (RR = 1.53; 95% CI: 1.16-2.01; P = 0.002). There was no difference in all-cause mortality between the two groups (RR = 0.95; 95% CI: 0.86-1.06; P = 0.36). No publication bias was observed through Begg's funnel plot. Higher dose of statins was found to be associated with the risk of ICH. Future studies are needed to confirm these findings.

Effects of atorvastatin on chronic subdural hematoma

“…[14,18,19] A previous meta-analysis with 7 RCTs included have found that atorvastatin 80 mg/d can increase the risk of intracerebral hemorrhage. [35] In this review, all the included studies have taken atorvastatin 20 mg/d as the intervention, and no studies have reported related adverse events. In the future, more high-quality RCTs, with dosage and duration analysis, taking atorvastatin as an adjunct to surgery or as a monotherapy, are needed when assessing the efficacy of atorvastatin.…”

Genetically Elevated LDL Associates with Lower Risk of Intracerebral Hemorrhage

“…3 In addition, clinical trials investigating statins as the primary cardiovascular disease prevention strategy have yielded inconsistent results for ICH risk. [4][5][6] Results from several observational studies evaluating data from a large number of ICH cases also reported inverse associations between lipid levels and ICH risk. The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study reported a one third lower ICH risk among study participants with a medical history of hypercholesterolemia.…”

Premorbid Use of Statin and Outcome of Acute Ischemic Stroke After Intravenous Thrombolysis: A Meta-Analysis

“…A previous study showed that statin users had a higher risk of gastrointestinal hemorrhage than other chronic medication users (42). Moreover, in patients with CVD, a meta-analysis of seven RCTs showed that a higher dose of statins was associated with a risk of intracranial hemorrhage (ICH) (43). Previous studies also showed that a lower serum LDL-C may be associated with a higher risk of ICH (44,45).…”