Background and objectives: Migraine is linked to higher risks of myocardial infarction and ischemic stroke, but it is uncertain whether this risk is due to nonsteroidal anti-inflammatory drug (NSAID) use. This study aimed to examine the cardiovascular risks associated with migraine during time with and without NSAID use.
Methods: We conducted a Danish nationwide population-based cohort study of individuals with a first-time hospital diagnosis of migraine (hospital-diagnosed) or at least 2 prescription fillings for migraine medication (primary care-diagnosed) between 1995 and 2021. We included comparison cohorts matched by birth year and sex from the general population. Exclusion criteria included previous migraine diagnosis, at least 2 prescription fillings for migraine medication, myocardial infarction, or ischemic stroke. We used the Aalen-Johansen estimator to calculate absolute risks and Cox regression to estimate adjusted hazard ratios (aHRs) for the association between migraine and the outcomes.
Results: The study included 46,647 individuals with hospital-diagnosed migraine and 186,588 matched comparisons and 288,529 individuals with primary care-diagnosed migraine and 1,154,116 matched comparisons. Those with hospital-diagnosed migraine had higher 20-year risks of myocardial infarction (3.3% vs 2.2%; aHR 1.53; 95% CI 1.40-1.67) and ischemic stroke (4.5% vs 2.4%; aHR 1.94; 95% CI 1.80-2.10) than comparisons. These increased risks were comparable during time with and without NSAID use for myocardial infarction. For ischemic stroke, the point estimate remained increased during time with and without NSAID use, although it seemed higher during time without NSAID use (aHR 1.97; 95% CI 1.82-2.13) than with NSAID use (aHR 1.49; 95% CI 1.13-1.97). Individuals with primary care-diagnosed migraine overall did not have higher risks of the outcomes than comparisons, regardless of NSAID use.
Discussion: The increased risk of myocardial infarction and ischemic stroke associated with hospital-diagnosed migraine could not be explained by NSAID-associated cardiovascular risks.
Classification of evidence: This study provides Class III evidence that NSAID-associated cardiovascular risks cannot explain the association between migraine and myocardial infarction or ischemic stroke.