Safety of Triptans in Patients Who Have or Are at High Risk for Cardiovascular Disease: A Target Trial Emulation

Objective: To evaluate the safety of triptans in migraine patients with cardiovascular disease or elevated cardiovascular risk.

Patients and methods: We retrieved data from a multistate US-based health system (January 2000 to August 2022) on adults with migraine and confirmed cardiovascular/cerebrovascular disease, or at least two cardiovascular risk factors. We compared the effect of triptans to nontriptan treatments on major adverse cardiovascular events (MACE) and its components at 60 days of starting treatments. We emulated a target trial and used propensity score matching for analysis.

Results: The 3518 patients in the triptan group were matched to the 3518 patients in the nontriptan group (median age, 55 years; 80.60% female). At 60 days, 52 patients (1.48%) in the triptan group had MACE, compared with 13 patients (0.37%) in the nontriptan group (relative risk [RR], 4.00; 95% CI, 2.24 to 7.14). Patients treated with triptans also had significantly higher risk of nonfatal myocardial infarction (15 patients (0.43%) vs 0 patients (0.00%)); heart failure (RR, 4.50; 95% CI, 1.91 to 10.61); and nonfatal stroke (RR, 8.00; 95% CI, 1.00 to 63.96). Five patients (0.14%) in each group died. The findings were consistent when analyses were restricted to sumatriptan, oral administration of triptan, patients with chronic migraine, history of cardiovascular disease, or history of cerebrovascular disease.

Conclusion: Triptans likely increase the risk of MACE; however, the incidence of MACE remains low in migraine patients with cardiovascular disease or elevated cardiovascular risk.

Trial registration: Treatments of Migraine With Triptans in Individuals With Elevated Cardiovascular Risk and in Pregnant Women.

Clinicaltrials: gov Identifier: NCT05854992 (https://classic.

Clinicaltrials: gov/ct2/show/NCT05854992).