Anti-CGRP mAbs Are Not Linked to Increased CVD Risk in Adults with Migraine

A study showed that anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are not linked to an increased CVD risk in patients with migraine, addressing earlier concerns about their potential cardiovascular effects.1

“Our comprehensive analyses with consistent findings provide important insights and evidence regarding the cardiovascular safety of anti-CGRP in real-world settings, particularly among populations often excluded from RCTs, such as older adults and individuals with disability,” wrote investigators, led by Seonkyeong Yang, PhD, from the department of pharmaceutical outcomes and policy at the University of Florida.

Monoclonal antibodies targeting CGRP or its receptor are an effective preventive migraine treatment, but concerns have surfaced about these antibodies’ harmful cardiovascular effects due to CGRP blockage.2 People worried that anti-CGRP mAbs may worsen preexisting hypertension, induce new-onset hypertension, or progress transient mild ischemia to myocardial infarction or stroke.1

Investigators conducted a retrospective, sequential cohort to compare the incidence of cardiovascular disease among individuals with migraine who initiated anti-CGRP-mAbs vs onabotulinumtoxinA in the US. Investigators grouped 266,848 participants into 5 cohorts based on sequential 6-month calendar intervals to reduce bias of new drug introductions and the COVID-19 pandemic.

The study included fee-for-service Medicare beneficiaries (between May 2018 and December 2020) aged ≥ 18 years with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Beneficiaries were excluded if they had a history of myocardial infarction, stroke, cluster headache, cancer, or hospital service within 1 year before treatment initiation.

The primary outcome was the time to first myocardial infarction or stroke. Secondary outcomes included hypertensive crisis, peripheral revascularization, and Raynaud phenomenon.

Among patients who initiated anti-CGRP mAbs (n = 5153), the mean age was 57.8 years and 83.6% were female. The most common anti-CGRP mAb inhibitor was erenumab (60.4%), followed by galcanezumab (29.5%), fremanezumab (9.8%), and eptinezumab (0.4%). In the onabotulinumtoxinA group (n = 4000), participants had a mean age of 61.9 years and 83.8% were females.

Participants on anti-CGRP mAb inhibitors were more likely to have a disability (67.6% vs 56%), full Part D LIS eligibility (54.9% vs 39.7%), and obesity (37.0% vs 30.4% compared with participants on onabotulinumtoxinA initiators. Moreover, participants on anti-CGRP mAb had a lower prevalence of pain conditions, such as fibromyalgia (17.0% vs 23.4%), and chronic migraine (46.3% vs 59.5%).

The crude incidence rates of the composite CVD outcome per 1000 person-years were 5.83 (95% CI, 3.62-9.38) among anti-CGRP mAb initiators vs 6.81 (95% CI, 4.24-10.96) among onabotulinumtoxinA initiators.

Compared with onabotulinumtoxinA, anti-CGRP mAbs were not linked to an increased risk of composite CVD events (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [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). Investigators also observed no risk differences for participants on anti-CGRP mAbs vs onabotulinumtoxinA initiators when assessing myocardial infarction (aHR, 0.86; 95% CI, 0.30 – 2.48) or stroke (aHR, 0.90; 95% CI, 0.35 – 2.27) separately.

Subgroup analyses showed consistent findings for individuals aged ≥ 65 years and those with established CVD.

Investigators emphasized the importance of post-approval observational studies using real-world data, recognizing that clinical trials typically include populations with fewer cardiovascular concerns.

“These studies are crucial for obtaining a comprehensive understanding of relatively rare CVD events that require long-term follow-up to establish the safety profile of anti-CGRP mAbs,” investigators concluded. “Future studies should leverage more recent data to assess the long-term safety of anti-CGRP mAbs in larger samples.”

References

1. Yang S, Orlova Y, Park H, et al. Cardiovascular Safety of Anti-CGRP Monoclonal Antibodies in Older Adults or Adults With Disability With Migraine. JAMA Neurol. Published online January 06, 2025. doi:10.1001/jamaneurol.2024.4537
2. Smillie SJ, King R, Kodji X, Outzen E, Pozsgai G, Fernandes E, Marshall N, de Winter P, Heads RJ, Dessapt-Baradez C, Gnudi L, Sams A, Shah AM, Siow RC, Brain SD. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress. Hypertension. 2014 May;63(5):1056-62. doi: 10.1161/HYPERTENSIONAHA.113.02517. Epub 2014 Feb 10. PMID: 24516108.