Risk of Ischaemic Stroke in People with Migraine with Aura

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). The type of migraine was not classified.

In another meta-analysis 2 (25 trials) migraine as a risk factor of stroke was assessed. Risk ratio was increased for migraine with aura, RR 2.16, 95% CI 1.53 to 3.03, but was not increased for patients without aura. Females were found to be at higher risk (RR 2.08; 95% CI 1.13 to 3.84), risk was increased with 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. Compared with non-migraineurs, the odds ratio of stroke for migraine with aura was 2.25 (95% CI 1.53 to 3.33), in migraine without aura there was a nonsignificant trend only (OR 1.24, 95% CI 0.86 to 2.43). OR for the female gender was 2.43 (CI 95% 1.80 to 3.27).

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), However, in migraine without aura the use of COC did not increase the risk (migraine without aura with COC RR 1.8, 95% CI 1.1 to 2.9, and migraine without aura without COC RR 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. For women with migraine with aura, consensus statement writers (European Headache Federation and the European Society of Contraception and Reproductive Health) suggest against of combined hormonal contraceptives. Instead, non-hormonal contraception or progestogen-only contraceptives are suggested.

Comment: The quality of evidence is upgraded by large magnitude of effect and by dose-response 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]
• 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]