Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort Study

Circulation. 2015 Jun 9;131(23):2070-8. doi: 10.1161/CIRCULATIONAHA.114.013046. Epub 2015 Apr 9.

Abstract

Background: Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke.

Methods and results: Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]).

Conclusions: In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution.

Keywords: Taiwan; cohort studies; hydroxymethylglutaryl-CoA reductase inhibitors; intracranial hemorrhages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / epidemiology
  • Incidence
  • Intracranial Hemorrhages / epidemiology*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Taiwan / epidemiology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors