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Evidence summaries

Risk of Ischaemic Stroke in People with Migraine

Migraine with aura appears to be a risk factor for ischaemic stroke. Smoking or use of combined hormonal contraception appears to increase the risk multifold. Level of evidence: "B"

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).

Absolute risk of stroke

No migraineMigraine with auraMigraine without aura
Without hormonal contraception2.5/100 0005.9/100 0004.0/100 000
With hormonal contraception6.3/100 00036.9/100 00025.4/100 000

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]

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