Migraine and hemorrhagic stroke: a meta-analysis

Background and Purpose—Several studies have assessed the possible increased risk of hemorrhagic stroke in migraineurs, drawing differing conclusions. No meta-analysis on the topic has been published to date. Methods—Multiple electronic databases (MEDLINE, EMBASE, Science Citation Index, and the Cochrane Library) were systematically searched up to March 2013 for studies dealing with migraine and hemorrhagic stroke. We selected case– control and cohort studies with a clear definition of the diagnostic criteria for migraine and hemorrhagic stroke, using an adjusted model or a matching procedure that could control for potential confounders, and reporting effect estimates with 95% confidence intervals (CIs) or enough data to allow calculation of those numbers. Adjusted odds ratios and hazard ratios were used to estimate effect size. Results—Of 11 264 records, we identified 8 studies (4 case–control and 4 cohort studies) involving a total of 1600 hemorrhagic strokes, which were included in the meta-analysis. The overall pooled adjusted effect estimate of hemorrhagic stroke in subjects with any migraine versus control subjects was 1.48 (95% CI, 1.16–1.88; P=0.002), with moderate statistical heterogeneity (I2=54.7%; P value for Q test=0.031). The risk of hemorrhagic stroke in subjects with migraine with aura (1.62; 95% CI, 0.87–3.03; P=0.129) was not significant. Compared with control subjects, the risk of hemorrhagic stroke was greater in females with any migraine (1.55; 95% CI, 1.16–2.07; P=0.003) and in female migraineurs aged less than 45 years (1.57; 95% CI, 1.10–2.24; P=0.012). Conclusions—Available studies suggest that subjects with migraine have an increased risk of hemorrhagic stroke. Further studies are needed to address the hemorrhagic stroke risk according to migraine type, age, sex, and hemorrhagic stroke type.