Stroke, MI risk varies based on contraception type

Estrogen-progestin contraceptives are associated with an increased risk of ischemic stroke and myocardial infarction (MI), while levonorgestrel-releasing intrauterine devices (IUDs) are not associated with either outcome, according to a prospective cohort study.

Researchers assessed six Danish national registries and collected data on women ages 15 to 49 years who lived in the country between 1996 and 2021. All women had no history of arterial or venous thrombosis, antipsychotic use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, or hysterectomy. A total of 2,025,691 women were followed for 22,209,697 person years. Findings were published by The BMJ on February 12.

Throughout the study period, 4,730 ischemic strokes and 2,072 MIs occurred. Ninety-three women (2%) who developed ischemic stroke and 185 (8.9%) who had an MI died within 30 days of diagnosis. Standardized ischemic stroke rates per 100,000 person-years were 18 (95% CI, 18 to 19) for no contraception, 39 (95% CI, 36 to 42) for combined oral contraception, 33 (95% CI, 25 to 44) for progestin-only pills, and 23 (95% CI, 17 to 29) for IUDs. Rates of MI per 100,000 person-years were 8 (95% CI, 8 to 9) for no contraception, 18 (95% CI, 16 to 20) for combined oral contraception, 13 (95% CI, 8 to 19) for progestin-only pills, and 11 (95% CI, 7 to 16) for IUDs.

Use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (95% CI, 1.9 to 2.2) for ischemic stroke and 2.0 (95% CI, 1.7 to 2.2) for MI compared with no use, corresponding to standardized rate differences of 21 (95% CI, 18 to 24) extra ischemic strokes and 10 (95% CI, 7 to 12) extra MIs per 100,000 person-years. Using progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI, 1.3 to 2.0) for ischemic stroke and 1.5 (95% CI, 1.1 to 2.1) for MI, equating to 15 (95% CI, 6 to 24) extra ischemic strokes and four (95% CI, −1 to 9) extra MIs per 100,000 person-years compared with no use. The researchers also found an increased arterial thrombotic risk with use of the combined vaginal ring, patch, and progestin-only implant; no increased risk was seen with the progestin-only IUD.

“Findings may suggest a dose-related association between progestin-only products and arterial thrombotic risk with the highest risk associated with implant use, then pills,” the authors wrote.

Limitations to the study include its observational nature and potential for residual confounding. Contraception exposure time was also defined by purchase records, which may have led to misclassification, especially for long-acting contraception.

“Although absolute risks were low, clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method,” the authors concluded.

An accompanying editorial commended the size of the study along with its length of follow-up. The editorialists reiterated that the absolute risk of MI and ischemic stroke with contraception remains low. “Nonetheless, these side effects are serious and given that approximately 248 million women use hormonal contraceptives daily, the results carry important implications. Contraceptive counselling requires a careful assessment of individual risk factors, such as pre-existing cardiovascular risk factors, including hypertension, obesity, or smoking,” they wrote.