In a study of over 108,000 migraine patients, erenumab showed no increased risk of hypertension, heart attack, or stroke compared to other migraine preventive medications.
108,019 patientsOne of the largest real-world studies of anti-CGRP drug cardiovascular safety, finding no increased risk of heart attack, stroke, or hypertension with erenumab
What the researchers found
Among 108,019 new users of migraine preventive medications, the 12-month unadjusted risk of new-onset hypertension was essentially identical across treatment groups: erenumab 9.34%, other anti-CGRP mAbs 9.42%, standard oral preventives 9.09%, and onabotulinumtoxinA 9.10%.
At 36 months, adjusted relative risks for acute myocardial infarction and stroke showed no significant differences: erenumab vs. other mAbs — MI: RR 1.02 (95% CI 0.45–1.59), stroke: RR 0.90 (0.56–1.25); erenumab vs. onabotulinumtoxinA — MI: RR 0.87 (0.19–1.55), stroke: RR 0.97 (0.42–1.52). No elevated cardiovascular risk was identified for erenumab.
Why it matters
CGRP is a potent vasodilator, raising theoretical concerns that blocking it with drugs like erenumab could cause blood vessel constriction and cardiovascular events. This large real-world study provides reassuring evidence that these concerns have not materialized in clinical practice, supporting continued confidence in anti-CGRP migraine therapies for the millions of patients who use them.
How the study worked
Retrospective observational cohort study using the MarketScan Commercial and Medicare Supplemental medical claims database. Researchers compared new-onset rates of hypertension, acute myocardial infarction, and stroke among new users of erenumab, other anti-CGRP mAbs, standard oral preventive medications, and onabotulinumtoxinA. Inverse probability weighting addressed measured confounders, and negative control outcome analyses evaluated unmeasured confounding.
What this study cannot tell us
This is an observational study using insurance claims data, which may have coding inaccuracies and cannot capture all clinical variables. While negative control outcomes suggested minimal unmeasured confounding for key comparisons, residual confounding cannot be entirely excluded. The comparison with standard oral preventives showed potential confounding concerns. The study population may not fully represent uninsured or underinsured patients.
How to read the evidence
This is a large retrospective observational cohort study using real-world claims data. While not a randomized controlled trial, the very large sample size, multiple comparator groups, inverse probability weighting, and negative control outcome analyses provide strong observational evidence.
When this study was published
Published in 2025, this study provides the most recent real-world cardiovascular safety data for erenumab, with follow-up extending to 36 months after treatment initiation.
The bigger picture
Anti-CGRP therapies have revolutionized migraine prevention, but cardiovascular safety questions have lingered since their approval. This study joins a growing body of evidence confirming that blocking the CGRP pathway does not increase cardiovascular risk in migraine patients, helping solidify these peptide-targeted drugs as first-line preventive options.
Questions still open
- Is the cardiovascular safety profile of anti-CGRP drugs maintained in patients with pre-existing cardiovascular disease, who were likely underrepresented in this cohort?
- Do longer treatment durations beyond 36 months reveal any emerging cardiovascular signals?
- Are there subpopulations (e.g., elderly, patients with vascular risk factors) where CGRP inhibition might pose greater cardiovascular risk?
Common questions
Is erenumab safe for the heart?
Why was there a concern about cardiovascular risk with anti-CGRP drugs?
Read the original research
Effect of erenumab versus other migraine preventive medications on cardiovascular and cerebrovascular outcomes: A United States claims database-based observational cohort study.
Headache, 65(6), 919-932
Citation
Dodick, David W; Tepper, Stewart J; Ailani, Jessica; Khodavirdi, Ani C; Pannacciulli, Nico; Fu, Alan; Kent, Shia T; Gill, Karminder; Urman, Robert; Oh, Sam S. (2025). Effect of erenumab versus other migraine preventive medications on cardiovascular and cerebrovascular outcomes: A United States claims database-based observational cohort study.. Headache, 65(6), 919-932. https://doi.org/10.1111/head.14912