CGRP Therapies for Migraine: Cerebrovascular and Cardiovascular Safety Reviewed in New Report
In a narrative review article published in Neurology, researchers examined the cardiovascular and cerebrovascular safety of calcitonin gene-related peptide (CGRP)–targeted therapies for people with migraine and vascular risk factors or a history of stroke. The authors note that CGRP-targeted therapies such as monoclonal antibodies (mAbs) and gepants—now widely used for migraine prevention—generally show favorable safety profiles in healthy populations. However, data remain limited in individuals with established cardiovascular disease, prior cerebrovascular events, or high vascular risk. Given CGRP’s potential protective role in ischemic conditions, the review emphasizes caution when using therapies that inhibit the CGRP pathway in certain high-risk groups.
The researchers synthesized findings from randomized clinical trials, observational studies, case reports, and preclinical research. The narrative review compared CGRP-targeted agents with traditional migraine preventives, highlights gaps in evidence—particularly for patients with stroke or subarachnoid hemorrhage—and provides structured clinical guidance. The review also addresses the emerging use of dual CGRP blockade with mAbs and gepants, discussing possible implications for cerebrovascular health.
Key points from the review include:
- General safety: Large randomized trials involving more than 10,000 patients show no overall increase in cardiovascular or cerebrovascular risk with CGRP mAbs or gepants in lower-risk populations.
- Stroke considerations:
- In acute or recent stroke (including subarachnoid hemorrhage), CGRP-targeted treatments should be paused; reinitiation may be considered after at least 3 months, depending on stroke etiology and patient factors.
- Patients with small vessel disease, distal arterial stenosis, or Raynaud phenomenon should avoid these therapies.
- Older patients and comorbidities: Those aged ≥65 years or with cardiovascular disease should generally avoid reinitiating CGRP-targeted therapy unless benefits outweigh risks; gepants with shorter half-lives may be preferred.
- High-risk acute migraine treatment: In patients with significant stroke risk or poststroke, gepants or ditans may be safer acute options compared with nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans, which have vasoconstrictive effects.
Source: Eller MT, Schwarzova K, Gufler L, et al. CGRP-targeted migraine therapies in patients with vascular risk factors or stroke: a review. Neurology. 2025;105(2):e213852(1)-e213852(9). https://doi.org/10.1212/WNL.0000000000213852