Risk of Ischaemic Stroke in People with Migraine

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).

Comment: The quality of evidence is upgraded by large magnitude of effect.

References

• Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 2005 Jan 8;330(7482):63. [PubMed]
• Schürks M, Rist PM, Bigal ME et al. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 2009;339():b3914. [PubMed]
• Spector JT, Kahn SR, Jones MR et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 2010;123(7):612-24. [PubMed]
• Sacco S, Ornello R, Ripa P et al. Migraine and hemorrhagic stroke: a meta-analysis. Stroke 2013;44(11):3032-8. [PubMed]
• Champaloux SW, Tepper NK, Monsour M et al. Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke. Am J Obstet Gynecol 2017;216(5):489.e1-489.e7. [PubMed]
• Sacco S, Merki-Feld GS, Ægidius KL et al. Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC). J Headache Pain 2017;18(1):108. [PubMed]