OBJECTIVE: To evaluate the association between contemporary hormonal contraceptive use and the risk of incident ischaemic stroke and myocardial infarction.
DESIGN: Real-world, nationwide, prospective cohort study.
SETTING: Denmark, by use of national registries.
PARTICIPANTS: All women aged 15-49 years residing in Denmark between 1996 and 2021, with no history of arterial or venous thrombosis, antipsychotics use, cancer, thrombophilia, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, hormone therapy use, oophorectomy, and hysterectomy.
MAIN OUTCOME MEASURES: First time diagnosis of ischaemic stroke or myocardial infarction at discharge.
RESULTS: Among 2 025 691 women followed up for 22 209 697 person years, 4730 ischaemic strokes and 2072 myocardial infarctions occurred. Standardised ischaemic stroke rate per 100 000 person years were 18 (95% confidence interval 18 to 19) for no use, 39 (36 to 42) for combined oral contraception, 33 (25 to 44) for progestin-only pills, and 23 (17 to 29) for intrauterine device. Standardised myocardial infarction rate per 100 000 person years were 8 (8 to 9) for no use, 18 (16 to 20) for combined oral contraception, 13 (8 to 19) for progestin-only pills, and 11 (7 to 16) for intrauterine device. Compared with no use, current use of combined oral contraception was associated with an adjusted rate ratio of 2.0 (1.9 to 2.2) for ischaemic stroke and 2.0 (1.7 to 2.2) for myocardial infarction. These corresponded to standardised rate differences of 21 (18 to 24) extra ischaemic strokes and 10 (7 to 12) extra myocardial infarctions per 100 000 person years. Compared with no use, current use of progestin-only pills was associated with an adjusted rate ratio of 1.6 (95% CI 1.3 to 2.0) for ischaemic stroke and 1.5 (1.1 to 2.1) for myocardial infarction, equating to 15 (6 to 24) extra ischaemic strokes and four (-1 to 9) extra myocardial infarctions per 100 000 person years. Increased arterial thrombotic risk was also observed with use of the combined vaginal ring (adjusted incidence rate ratio of 2.4 (1.5 to 3.7) for ischaemic stroke and 3.8 (2.0 to 7.3) for myocardial infarction), patch (3.4 (1.3 to 9.1) and no myocardial infarctions), and progestin-only implant (2.1 (1.2 to 3.8) and =3 myocardial infarctions), whereas no increased risk was observed with progestin-only intrauterine device (1.1 (1.0 to 1.3) for ischaemic stroke and 1.1 (0.9 to 1.3) for myocardial infarction).
CONCLUSIONS: Use of contemporary oestrogen-progestin and progestin-only contraceptives was associated with an increased risk of ischaemic stroke and, in some cases, myocardial infarction except for the levonorgestrel-releasing intrauterine device, which was not associated with either. 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.
| Discipline Area | Score |
|---|---|
| Public Health |  |
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Gynecology | Coming Soon... |
I was interested to read that ORs for stroke and MI are similar with combined OCP AND most progestogen-only methods.
This was interesting because I take care of young women who need contraception. It will not change my current practice. Culturally, women accept OCPs easily. Compared with pregnancy, the risks of contraception are lower. I will pay more attention to cardiovascular risks in young women.
These results nudge primary care providers to weigh closely the benefits vs risks of hormone contraception, particularly combined forms. The results also raise concern that the duration of home contraception use is not relevant.
Helpful article but no matter how large the population numbers are, it still has the same limitations as any other observational study and may lead to erroneous conclusions. Importantly, overwhelmingly the literature shows that progestin-only products do not increase thrombotic risks (with two exceptions: 1. norethindrone acetate used at high doses for bleeding treatment as opposed to contraception; and 2. Depo-Provera, given its high dose formulation). It is likely that in this observational study the progestin-only methods showed up as increased thrombotic risks because they are often used in patients who are at higher thrombotic risks at baseline, hence the reason clinicians don't feel comfortable offering estrogen. This is a huge potential confounder.
This is an update of a 2012 cohort. A really important update for very commonly used medicines.
Very important national Danish cohort study showing that oestrogen-progestin and progestin-only contraceptives, except for the levonorgestrel-releasing intrauterine device, were associated with an increased risk of arterial thrombotic events. The highest risk estimates were observed with oestrogen-containing products. The duration of use did not seem to influence the risk of an arterial thrombotic event.
