Objective:

To characterize patient demographics and vascular risk in individuals with migraine prescribed calcitonin gene-related peptide (CGRP) inhibitors, including monoclonal antibodies (mAbs) and antagonists (gepants).

Background:

In March 2025, FDA labeling for gepants was updated to include potential risks of hypertension (HTN) and Raynaud’s phenomenon (RP). The CGRP mAb erenumab label also warns of new-onset or worsening HTN. Real-world evidence comparing vascular risk between mAbs and gepants remains limited.

Design/Methods:

We conducted a cross-sectional study using the TriNetX® database to identify adults with migraine (ICD-10 G43) prescribed CGRP mAbs (erenumab, galcanezumab, fremanezumab, eptinezumab) or gepants (atogepant, rimegepant). Demographics, comorbidities, and medication profiles were balanced via 1:1 nearest-neighbor propensity score matching. Relative risk ratios (RR, 95% confidence interval) for incident HTN, RP, and stroke following the index event were calculated, excluding patients with prior vascular diagnoses.

Results:

Matched cohorts included 146,934 patients. Compared to gepants, mAbs were associated with a higher RR of HTN (1.43, 1.39–1.47), RP (1.47, 1.36–1.59), and stroke (1.31, 1.22–1.40). Never-CGRP users compared to mAb users had increased RR of HTN (1.80, 1.68–1.93) and stroke (1.92, 1.69–2.18), with similar RP (1.07, 0.89–1.29). Never-CGRP users compared to gepant users had a higher RR of HTN (RR 2.15, 2.04–2.27), RP (1.25, 1.08–1.44), and stroke (1.29, 1.20–1.40).

Conclusions:

CGRP mAbs were linked to greater vascular risk than gepants. Elevated risk among never-users may reflect underlying clinical characteristics, prescribing patterns, and possibly a protective effect of CGRP inhibitors. These findings stress the need for prospective studies to clarify causality and guide vascular safety monitoring.