Calcitonin Gene-Related Peptide Inhibitors and Cardiovascular Events in Patients With Migraine: A Retrospective, Observational Cohort Study.

BACKGROUND AND OBJECTIVES: Calcitonin gene-related peptide (CGRP) inhibitors have entered widespread use in the United States for treatment of migraine, but data on their cardiovascular risk profile are lacking. The objective of this study was to determine whether exposure to a CGRP inhibitor is associated with cardiovascular events in patients with migraine. METHODS: A retrospective, observational, cohort study was conducted using computerized claims data from a proprietary, insurance-based registry, MarketScan (by Merative). Beneficiaries with at least one claim related to a migraine diagnosis and continuous coverage for at least 12 months before migraine diagnosis were included. Using a sequential trial framework, the rate of cardiovascular events was computed in those who did and did not initiate a CGRP inhibitor, using both crude estimates and those derived in propensity score overlap-weighted cohorts. Adjusted hazard ratios (HR) and corresponding 95% CI were computed. The principal exposure was initiation of any CGRP inhibitor. The primary end point was a composite of myocardial infarction (MI), cerebral ischemic stroke, revascularization, peripheral arterial disease, or central retinal artery occlusion (CRAO). Secondary end points included each component individually. A falsification end point (humeral fracture) was included. RESULTS: In total, 900,370 beneficiaries (median age 41 [Q1, Q3: 31, 51] years; 77.8% female) were included, of whom 58,679 initiated a CGRP inhibitor and 841,691 did not initiate a CGRP inhibitor during the study period. Beneficiaries initiating a CGRP inhibitor exhibited a greater degree of cardiovascular morbidity at baseline than noninitiators. In the overlap-weighted analysis, there was a higher rate of the primary end point among beneficiaries who initiated a CGRP inhibitor (8.77 events/1,000 person-years vs 6.76 events/1,000 person-years; aHR 1.26 [95% CI 1.10-1.45]). Initiation of a CGRP inhibitor was associated with a significantly higher rate of one secondary end point (ischemic stroke [aHR 1.26 (95% CI 1.07-1.49)]) but not 4 other secondary end points: MI, revascularization, CRAO, and intracranial hemorrhage. DISCUSSION: In a nationwide cohort study, initiation of a CGRP inhibitor was associated with an increased risk of a composite of cardiovascular events; however, the magnitude of the increased risk was low. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with migraine, initiation of a CGRP inhibitor was associated with a modestly increased risk of a composite of cardiovascular events.