Statins and intracerebral hemorrhage: Collaborative systematic review and meta-analysis

Daniel G. Hackam, Mark Woodward, L. Kristin Newby, Deepak L. Bhatt, Mingyuan Shao, Eric E. Smith, Allan Donner, Muhammad Mamdani, James D. Douketis, Hisatomi Arima, John Chalmers, Stephen MacMahon, David L. Tirschwell, Bruce M. Psaty, Cheryl D. Bushnell, Maria I. Aguilar, Dan J. Capampangan, David J. Werring, Paola De Rango, Anand ViswanathanNicolas Danchin, Ching Lan Cheng, Yea Huei Kao Yang, B. Marianne Verdel, Mei Shu Lai, James Kennedy, Shinichiro Uchiyama, Takenori Yamaguchi, Yasuo Ikeda, Marko Mrkobrada

Research output: Contribution to journalReview articlepeer-review

141 Citations (Scopus)


Background-: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. Methods and Results-: We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I 2=66%, P=0.01), but not for the cohort studies (I 2=0%, P=0.48) or randomized trials (I 2=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. Conclusions-: We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.

Original languageEnglish
Pages (from-to)2233-2242
Number of pages10
Issue number20
Publication statusPublished - 15 Nov 2011
Externally publishedYes


  • cerebrovascular disorders
  • hemorrhage
  • meta-analysis
  • statins


Dive into the research topics of 'Statins and intracerebral hemorrhage: Collaborative systematic review and meta-analysis'. Together they form a unique fingerprint.

Cite this