CGRP-Targeted Migraine Therapies in Patients With Vascular Risk Factors or Stroke

Calcitonin gene-related peptide (CGRP)-targeted therapies, including monoclonal antibodies (mAbs) and gepants, represent a major advancement in migraine prevention, offering greater efficacy and improved tolerability compared with traditional treatments. These agents selectively inhibit the CGRP pathway, a key mediator in migraine pathophysiology, and are increasingly used even as first-line options in selected patients. While clinical trials and real-world data suggest a favorable cardiovascular (CV) safety profile, particularly in patients without major risk factors, evidence remains limited for those with established vascular disease or recent vascular events. Concerns persist regarding long-term effects and the safety of CGRP blockade in high-risk populations. This narrative review focuses on the CV and cerebrovascular safety of CGRP-targeted migraine treatments-an area of growing clinical relevance. We compare these newer agents with traditional migraine preventives and highlight the paucity of data in patients with previous stroke, subarachnoid hemorrhage, myocardial infarction, or significant CV comorbidities. In addition, we discuss the emerging topic of dual CGRP pathway blockade (mAbs plus gepants), which has not previously been reviewed in the context of vascular risk. Based on currently available scientific evidence, we offer structured clinical considerations to guide the use of CGRP-targeted therapies in patients with vascular risk or cerebrovascular disease. Our aim is to support informed decision making in a population that has often been excluded from clinical trials but is becoming increasingly important in clinical practice.