Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Feb 1;82(2):132-141.
doi: 10.1001/jamaneurol.2024.4537.

Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine

Seonkyeong Yang  1 , Yulia Orlova  2 , Haesuk Park  1 , Steven M Smith  1   3 , Yi Guo  4 , Benjamin A Chapin  5   6 , Debbie L Wilson  1 , Wei-Hsuan Lo-Ciganic  6   7   8
Affiliations

Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine

Seonkyeong Yang et al. JAMA Neurol. .

Abstract

Importance: Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP mAbs) offer effective migraine-specific preventive treatment. However, concerns exist about their potential cardiovascular risks due to CGRP blockade.

Objective: To compare the incidence of cardiovascular disease (CVD) between Medicare beneficiaries with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US.

Design, setting, and participants: This retrospective, sequential cohort study was conducted among a nationally representative population-based sample of Medicare claims from May 2018 through December 2020. Data analysis was performed from August to December 2023. This study included fee-for-service Medicare beneficiaries aged 18 years or older with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Beneficiaries who had a history of myocardial infarction (MI), stroke, cluster headache, malignant cancer, or hospice service within a 1-year baseline period prior to treatment initiation were excluded. To minimize channeling bias from new drug introductions and time-related bias due to the COVID-19 pandemic, 5 cohorts were established, representing sequential 6-month calendar intervals based on the initial prescription or date of index anti-CGRP mAbs or onabotulinumtoxinA use.

Exposure: Anti-CGRP mAbs vs onabotulinumtoxinA.

Main outcomes and measures: The primary outcome was time to first MI or stroke. Secondary outcomes included hypertensive crisis, peripheral revascularization, and Raynaud phenomenon. The inverse probability of treatment-weighted Cox proportional hazards models were used to compare outcomes between the 2 treatment groups.

Results: Among 266 848 eligible patients with migraine, 5153 patients initiated anti-CGRP mAbs (mean [SD] age, 57.8 [14.0] years; 4308 female patients [83.6%]) and 4000 patients initiated onabotulinumtoxinA (mean [SD] age, 61.9 [13.7] years; 3353 female patients [83.8%]). Use of anti-CGRP mAbs was not associated with an increased risk of composite CVD events (adjusted hazard ratio [aHR], 0.88; 95% CI, 0.44-1.77), hypertensive crisis (aHR, 0.46; 95% CI, 0.14-1.55), peripheral revascularization (aHR, 1.50; 95% CI, 0.48-4.73), or Raynaud phenomenon (aHR, 0.75; 95% CI, 0.45-1.24) compared with onabotulinumtoxinA. Subgroup analyses by age group and presence of established non-MI or stroke CVD showed similar findings.

Conclusions and relevance: In this cohort study, despite initial concerns regarding the cardiovascular effects of CGRP blockade, anti-CGRP mAbs were not associated with an increased risk of CVD compared with onabotulinumtoxinA among adult Medicare beneficiaries with migraine, who were predominantly older adults or individuals with disability. Future studies with longer follow-up periods and in other populations are needed to confirm these findings.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Park reported grants from Arista Networks, the National Human Genome Research Institute, the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Drug Abuse (NIDA), the Sleep Foundation, and the University of Florida Clinical and Translational Science Institute (UF CTSI) outside the submitted work. Dr Smith reported grants from the NHLBI, the Patient-Centered Outcomes Research Institute (PCORI), and the US Department of Defense outside the submitted work. Dr Wilson reported grants from the Bristol Myers Squibb/Pfizer Alliance American Thrombosis Investigator Initiated Research Program, Merck Sharp & Dohme, the NIDA (R01DA050676 and 1R01DA057886), the National Institute on Aging (NIA) (R21AG060308), the Sleep Research Society Foundation, and the US Department of Veterans Affairs (AGR DTD 04-26-2023) outside the submitted work and serving on the editorial board of the Journal of Pharmacy Technology. Dr Lo-Ciganic reported grants from Bristol Myers Squibb, Merck Sharp & Dohme, the NIA, the NIDA, the National Institute of Mental Health, the PCORI, the Pharmaceutical Research and Manufacturers of America Foundation, the Richard King Mellon Foundation, the Sleep Foundation, the UF CTSI, and the US Department of Veterans Affairs outside the submitted work; a pending patent for U1195.70174US00; uncompensated board membership by the Pharmacy Quality Alliance; and compensated consulting service for Teva Pharmaceuticals. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Sample Size Flowchart
CGRP indicates calcitonin gene-related peptide; CVD, cardiovascular disease; mAb, monoclonal antibody.
Figure 2.
Figure 2.. Forest Plot of the Risk of Cardiovascular Disease (CVD) Outcomes Associated With Anti–Calcitonin Gene-Related Peptide Monoclonal Antibodies Compared to OnabotulinumtoxinA
aHR indicates adjusted hazard ratio.
See this image and copyright information in PMC

References

    1. GBD 2016 Headache Collaborators . Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi: 10.1016/S1474-4422(18)30322-3 - DOI - PMC - PubMed
    1. Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022;23(1):34. doi: 10.1186/s10194-022-01402-2 - DOI - PMC - PubMed
    1. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society . The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039. doi: 10.1111/head.14153 - DOI - PubMed
    1. American Headache Society . The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18. doi: 10.1111/head.13456 - DOI - PubMed
    1. Fremanezumab. Package insert. Teva Pharmaceuticals; 2018.

MeSH terms

Substances