Evaluating the Risk of Ischemic Stroke With Low‐Dose Combined Oral Contraceptives in Women With Migraine: A Nationwide Claims Database Study
Sho Koyanagi, Takanori Yanai, Yoshihide Inayama, Sachiko Tanaka‐Mizuno, Koji KawakamiABSTRACT
Aim
Combined oral contraceptives (COCs) are often avoided in women with migraine because of concerns about ischemic stroke. However, the risk associated with low‐dose and ultra‐low‐dose COCs remains unclear. We aimed to evaluate the risk of ischemic stroke using contemporary low‐dose COC use among women with migraine.
Methods
We conducted a retrospective cohort study using the JMDC claims database in Japan. Women aged 20–49 years diagnosed with migraine between April 2012 and March 2024 were included. Exposure was defined as administration of COCs containing estrogen doses of 20 and 35 μg, whereas the comparison group was defined as discontinued use after the initial prescription. The hazard ratios (HRs) for ischemic stroke were estimated using Cox regression, and odds ratios (ORs) were calculated using case‐time‐control analysis to evaluate short‐term associations.
Results
Among the 215 536 women with migraine, 453 experienced ischemic strokes during follow‐up. Among COC continuing users, the 5‐year cumulative incidence rates of ischemic stroke were 0.11% (95% CI: 0.01% to 0.81%), and the HR was 0.10 (95% CI: 0.01 to 1.36). The OR in the case‐time‐control analysis was 0.38 (95% CI: 0.03 to 5.13).
Conclusions
This large claims database study found no significant increase in the risk of ischemic stroke or other outcomes associated with low‐dose COC use in women with migraine.