Stroke, MI Risk and Contraceptives: Latest Findings

The use of contemporary hormonal contraception is associated with a significantly increased relative risk for ischemic stroke and, in some cases, myocardial infarction (MI), a new real-world study showed.

The research included analysis of risk and use of combined oral contraceptive pills, vaginal ring, patch, progestin-only pills, and subcutaneous implant but not levonorgestrel-releasing intrauterine device.

The researchers stressed that while the absolute excess risks are low, given the widespread use of these products, “clinicians should include the potential risk of arterial thrombosis in their assessment of the benefits and risks when prescribing a hormonal contraceptive method,” they advised.

The study was published online on February 12 in The BMJ.

Mixed Literature

Worldwide, almost 250 million women are estimated to use hormonal contraception. Previous studies have yielded conflicting results, with some pointing to a possible link between their use and increased risk for ischemic stroke and MI, others showing no association, and still others suggesting a protective effect of hormonal contraception use.

To investigate further, Harman Yonis, MD, with Aalborg University Hospital in Aalborg, Denmark, and colleagues tracked national prescription records for more than 2 million Danish women aged 15-49 years from 1996 to 2021.

None of the women had a history of blood clots, cancer, liver disease, kidney disease, polycystic ovary syndrome, endometriosis, infertility treatment, antipsychotic use hormone therapy, oophorectomy, or hysterectomy.

During the study period, records showed 4730 ischemic strokes and 2072 MIs.

Compared with no hormonal contraceptive use, current use of combined estrogen-progestin oral contraception was associated with a twofold increase risk for ischemic stroke and MI (adjusted rate ratio (aRR), 2.0).

This equates to roughly one extra ischemic stroke for every 4760 women using the combined oral contraceptives per year and one extra MI for every 10,000 women per year of use compared with no use.

Current use of progestin-only oral contraceptives (vs no use) carried a slightly elevated risk though lower than the combined pills (ischemic stroke: aRR, 1.6; MI risk: aRR, 1.5) equating to 15 extra ischemic strokes and four extra MIs per 100,000 person years.

A separate analysis from the same research team published this week in JAMA Network Open and reported by Medscape Medical News showed some progesterone-only hormonal contraceptives may carry similar clot risk to certain combined pills.

In the current analysis, nonoral combined contraceptives, such as the vaginal ring and patch, had higher associated risks, with the vaginal ring increasing ischemic stroke risk 2.4-fold and MI risk 3.8-fold, whereas the patch increased ischemic stroke risk 3.4-fold.

No increased risk for stroke or MI was observed with the progestin-only intrauterine device. Duration of use did not seem to influence the risk.

Outside Experts Weigh In 

Writing in an accompanying editorial, Therese Johansson, PhD, with Royal Institute of Technology, Stockholm, Sweden, said the new data support “contraceptive counseling,” including careful assessment of individual risk factors, such as pre-existing cardiovascular risk factors including hypertension, obesity, and smoking.

A number of outside experts also weighed in on the findings in a statement from the UK Science Media Centre.

Sonya Babu-Narayan, BSc, MBBS, clinical director at the British Heart Foundation and consultant cardiologist, said this latest study “supports the current practice of recommending the option of a progestin intrauterine device” for women at high cardiovascular risk.

Angela Clerk, PhD, BSc, with University of Reading, Reading, England, said “This is clearly an important study but while the focus is on the potential negative effects of contraception on cardiovascular risk, it is also clear that any increase in risk is actually very small. This emphasizes the overall safety of the drugs, particularly when balanced against the negative effects of unwanted pregnancies resulting from a lack of contraception,” Clerk said.

Women should not stop using contraception based on the findings, Becky Mawson, MD, BSc, MBChB, with The University of Sheffield, Sheffield, England, said in the statement.

“The risk of stroke and heart attack in pregnancy and postnatal period is significantly higher than the risks reported in this study for contraceptives,” Mawson said. “For those using contraceptives for treatment of health conditions, the slightly increased risk needs to be balanced with the benefit in quality of life for those suffering debilitating gynecological and hormonal conditions.” 

This study was supported by the Danish health insurance association, Sygeforsikringen “Danmark.” Yonis has no relevant disclosures. Johansson, Mawson, Clerk and Babu-Narayan had no relevant conflicts of interest.