A systematic review and meta-analysis 1 included 14 studies (11 case-control studies and 3 cohort studies). The risk of stroke was increased in people with migraine (relative risk 2.16, 95% confidence interval 1.89 to 2.48). This increase was consistent in people who had migraine with aura (RR 2.27, 95% CI 1.61 to 3.19) and migraine without aura (RR 1.83, 95% CI 1.06 to 3.15), as well as in those taking combined oral contraceptives (COC) (RR 8.72, 95% CI 5.05 to 15.05).
In another meta-analysis 2 (25 trials) migraine as a risk factor of stroke was assessed. The demonstrated risk ratios were for migraine as a whole 1.73 (95% CI 1.31 to 2.29), for migraine with aura RR 2.16 (95% CI 1.53 to 3.03), and not statistically significant for patients without aura RR 1.23 (95% CI 0.90 to 1.69). Females were found to be at the highest risk (RR 2.08; 95% CI 1.13 to 3.84), females on oral contraceptives (RR 7.02; 95% CI 1.51 to 32.68), and in particular, if associated to the smoking habit (RR 9.03; 95% CI 4.22 to 19.34).
A third meta-analysis 3 included 21 studies (13 case-control studies and 8 cohort studies) with a total of 622 381 patients. A total adjusted odds ratio of stroke in migraineurs was 2.04 (95% CI 1.72 to 2.76), for migraine with aura 2.25 (95% CI 1.53 to 3.33), migraine without aura 1.24 (95% CI 0.86 to 2.43) compared with non-migraineurs. OR for the female gender was 2.43 (CI 95% 1.80 to 3.27).
Another meta-analysis 4 included 8 studies (4 case-control and 4 cohort studies) involving a total of 1600 hemorrhagic strokes. The overall pooled adjusted effect estimate of hemorrhagic stroke in subjects with any migraine versus control subjects was 1.48 (95% CI, 1.16 to 1.88; P=0.002; I² 54.7%); OR for migraine with aura 1.62 (95% CI, 0.87 to 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 to 2.07; P=0.003) and in female migraineurs aged less than 45 years (1.57; 95% CI, 1.10 to 2.24; P=0.012).
A case-control study 5 based on nationwide database assessed the risk of stroke associated with migraine and combined hormonal contraceptives. Years 2006 to 2012, there were 25 887 ischemic strokes among females ages 15-49 years. Compared to those with neither migraine nor combined hormonal contraceptive use, OR for ischemic stroke among those with migraine with aura using COC was 6.1 (95% CI 3.1 to 12.1); migraine with aura without COC 2.7 (95% CI 1.9 to 3.7), migraine without aura and COC 1.8 (95% CI 1.1 to 2.9), and migraine without aura without COC 2.2 (95% CI 1.9 to 2.7). The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor.
A consensus statement 6 evaluated absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contraception and migraine status (table T1).
| No migraine | Migraine with aura | Migraine without aura | |
| Without hormonal contraception | 2.5/100 000 | 5.9/100 000 | 4.0/100 000 |
| With hormonal contraception | 6.3/100 000 | 36.9/100 000 | 25.4/100 000 |
Comment: The quality of evidence is upgraded by large magnitude of effect.
Primary/Secondary Keywords