According to the authors of this systematic review and meta-analysis, there is no evidence that use of statins is associated with an increased risk of intracerebral haemorrhage (ICH); any risk if present is likely to be small and outweighed by the benefits of such therapy.

The authors note that a post hoc analysis of a large randomised controlled trial in patients with cerebrovascular disease suggested that the risk for haemorrhagic stroke was higher in patients receiving atorvastatin than in those randomised to placebo.  This finding has led to some uncertainty about the balance of benefits and risks of statins, particularly in those with cerebrovascular disease.  They therefore conducted a systematic review of published and unpublished data, both from randomised controlled trials and observational studies, to examine the association of statins with ICH.       

Researchers screened 17 databases from inception to June 2011 to identify eligible studies, used functions in the database to locate related articles, manually screened product monographs, review articles and treatment guidelines, and reviewed abstract proceedings of major cardiology, neurology and endocrinology meetings.  The authors of studies reporting rates of statin exposure and intracerebral haemorrhage in their publications but not reporting an exposure-outcome association were contacted and were able to supply the required information in the majority of cases.

Published and unpublished data from a total of 23 randomised trials and 19 observational studies were used in the study (a total of 248,391 patients and 14,784 ICHs).  Randomised trials, cohort studies, and case-control studies were analysed separately; only adjusted risk estimates were used for pooling observational data.  The main findings reported are as follows:
  

• The randomised studies provided a total of 526,518 patient-years of follow-up, with a median follow-up per trial of 3.9 years.  Statins were not associated with an increased risk of ICH in these studies (risk ratio 1.10; 95% CI 0.86–1.41); the equivalent absolute risk increase was 0.027% (95% CI -0.042 to 0.096).  There was no evidence of publication bias.

• The observational studies included 12 cohort studies, 6 case-control studies and one case-crossover study.  The cohort studies, which provided a total of 219,459 patient-years of follow-up (median of 3 years per study), did not find statins to be associated with an increased risk of ICH (0.94; 95% CI 0.81–1.10).

• There was also no evidence of an association between statin use and ICH in the case-control studies (0.60; 95% CI 0.41–0.88); however there was evidence of statistical heterogeneity for these studies (I2=66%, P=0.01),

• Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results.

The authors acknowledge the limitations of their study, for example the lack of access to individual patient data, poor adherence in observational studies may bias risk towards the null, and the lack of specific information on type of ICH so whether statin use could be associated with an increased risk of a particular subtype could not be investigated. 

They conclude that the lack of association between statin use and ICH was consistent across settings, statin regimens and study designs, and say that clinicians should continue to use treatment algorithms that base the initiation of statins on each individual’s global risk for cardiovascular events.