Combined oral contraceptives: the risk of myocardial infarction and ischemic stroke

Roach, Rachel E J; Helmerhorst, Frans M.; Lijfering, Willem M.; Algra, Ale; Dekkers, Olaf M.

doi:10.1002/14651858.cd011054

Cited by 50 publications

(45 citation statements)

References 25 publications

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“…The authors of the recent Cochrane review suggested that pills containing 30 mg of EE or less are the safest form of hormonal contraception, and available evidence suggests that 20 mg EE CHCs confer even lower risk. 41 Although all of the studies in this review found an increased risk of stroke in women with migraine who used CHCs, it should be noted that the absolute risk of stroke in reproductive-aged women is low. The crude, unadjusted incidence of stroke was 3.56 per 100,000 women of reproductive age per year in the UK population-based study by Nightingale and Farmer, and this is consistent with other studies specifically evaluating incidence in premenopausal women.…”

Section: Discussionmentioning

confidence: 78%

“…A more recent Cochrane review looked at 24 studies evaluating the effect of oral contraceptives on risk of myocardial infarction and ischemic stroke. 41 They also concluded that there is a risk of ischemic stroke with use of oral contraceptives, but a dose response was seen. The OR for risk of ischemic stroke or MI with 20 mg EE was 1.6 (95% CI 1.4-1.8), for 30-49 mg EE 2.0 (1.4, 3.0), and for >49 mg 2.4 (1.8, 3.3).…”

Section: Discussionmentioning

confidence: 99%

“…The OR for risk of ischemic stroke or MI with 20 mg EE was 1.6 (95% CI 1.4-1.8), for 30-49 mg EE 2.0 (1.4, 3.0), and for >49 mg 2.4 (1.8, 3.3). 41 Although there is good evidence that high doses of estrogen can increase the risk of arterial stroke, an increase in stroke risk is not clear at the lower (20-35 mg EE) estrogen doses used in modern contraceptives. One question is whether risk might vary by country, due to differences in CHC prescribing guidelines.…”

Section: Discussionmentioning

confidence: 99%

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Risk of Stroke Associated With Use of Estrogen Containing Contraceptives in Women With Migraine: A Systematic Review

et al. 2017

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Objective.-Migraine with aura has been associated with increased risk of ischemic and hemorrhagic stroke. Prior studies have shown a further increase in risk in women using combined hormonal contraceptives (CHCs). This has led to guidelines recommending against use of CHCs in this population. We sought to assess whether the risk of stroke is associated with the dose of estrogen and whether there is evidence of synergism between migraine and CHCs. We also sought to assess whether an interaction effect exists between migraine and CHCs.Methods.-We searched PubMed, the Cochrane Library, and EMBASE from inception through January 2016 for relevant English-language studies of adults, of any design. We included studies that examined exposure to CHCs and reported outcomes of ischemic or hemorrhagic stroke. Data extraction and assessment of study quality were conducted independently by reviewer pairs and quality was assessed with the GRADE and Newcastle Ottawa scales.Results.-Of 2480 records, 15 studies met inclusion criteria and six provided odds ratios for the relevant population. The point estimates for the odds ratios for ischemic stroke in women with migraine who used CHCs with any dose of estrogen ranged from 2.08 to 16.9. Studies were generally small and confidence intervals were wide. No studies reported odds ratios for stroke risk as a function of estrogen dose in women with migraine, largely due to insufficient sample sizes. No interaction effect between migraine and CHCs was seen in the seven studies that assessed this. One study differentiated risk by presence or absence of migraine aura and found an increased risk in the migraine with aura population (OR 6.1; CI 3.1 to 12.1 in migraine with aura vs 1.8; CI 1.1 to 2.9 in the migraine without aura group). Studies generally had high Newcastle Ottawa scores and low GRADE levels of evidence. No studies met all three supplementary quality criteria (assessed migraine subtype, used International Classification of Headache Disorders criteria for diagnosis of migraine, and stratified risk by estrogen dose).Conclusions.-This systematic review shows a lack of good quality studies assessing risk of stroke associated with low dose estrogen use in women with migraine. Further study in this area is needed. The available evidence is consistent with an additive increase in stroke risk with CHC use in women with migraine with aura. Since the absolute risk of stroke is low even in the presence of these risk factors, use of CHCs in women who have migraine with aura should be based on an individualized assessment of harms and benefits.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Risk of Stroke Associated With Use of Estrogen Containing Contraceptives in Women With Migraine: A Systematic Review

et al. 2017

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“…Though there has been debate 8,9 about whether different progestins impact the risk of venous thromboembolism differently the chosen progestin does not appear to affect arterial risks such as CVA or MI. 10 For an in-depth review of this issue, we will examine 3 sources: (1) a recent systematic review 6 of hormonal contraceptives in women with migraine (this was selected as an example of the typical systematic review of this topic; concerns and flaws will be pointed out as we go along), (2) a recent study 11 that specifically compares the safety of three discrete, new CHC formulations with an accepted low-risk option (this article was selected because it exemplifies the way CHCs should be compared as we go forward-specifically and individually rather than lumped together as "CHCs"), and (3) the most recent Cochrane review of stroke risk and CHCs. 10 Let's first examine the most recent 6 of the typical systematic reviews, taking a closer look at each selected article to identify confounding issues.…”

Section: Stroke Risk Related To Chcs: the Estrogen Dose Mattersmentioning

confidence: 99%

“…And, finally, we have the 2015 Cochrane Review, 10 which identified 1,298 publications assessing arterial risks in CHC users compared with nonusers. In their network meta-analysis, they included 28 publications reporting on 24 studies.…”

Section: Cochrane Reviewmentioning

confidence: 99%

Hormonal Contraceptives and Migraine With Aura—Is There Still a Risk?

Calhoun

2016

Headache

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Unnecessary confusion still surrounds the use of combined hormonal contraceptives (CHCs) in the setting of migraine with aura (MwA). Clearing this confusion is a key issue for headache specialists, since most women with migraine have menstrual-related migraine (MRM), and some CHCs can prevent this particularly severe migraine. Their use, however, is still restricted by current guidelines due to concerns of increased stroke risk - concerns that originated over half a century ago in the era of high dose contraceptives. Yet studies consistently show that stroke risk is not increased with today's very low dose CHCs containing 20-25 µg ethinyl estradiol (EE), and continuous ultra low-dose formulations (10-15 µg EE) may even reduce aura frequency, thereby potentially decreasing stroke risk. This article clarifies the stroke risk of CHCs and examines their impact on migraine. It also examines how stroke risk is altered by the estrogen content of the CHC, by contributing factors such as smoking, age and hypertension, and by aura frequency. And finally, it puts these risks into a meaningful context with a risk/benefit assessment.

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