Anti-CGRP monoclonal antibodies may not increase CVD risks among migraine patients compared to onabotulinumtoxinA: JAMA

Despite previous concerns surrounding the potential cardiovascular risks associated with CGRP (calcitonin gene-related peptide) blockade, the study found no significant increase in the risk of cardiovascular disease (CVD) when anti-CGRP mAbs were compared to onabotulinumtoxinA (Botox) in Medicare beneficiaries with migraine.

Monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide or its receptor (anti-CGRP mAbs) provide an effective migraine-specific preventive treatment. However, concerns about their potential cardiovascular risks due to CGRP blockade have persisted. Seonkyeong Yang, Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, and colleagues aimed to compare the incidence of cardiovascular disease among Medicare beneficiaries with migraine who initiated treatment with anti-CGRP mAbs versus onabotulinumtoxinA in the US.

For this purpose, the researchers conducted a retrospective cohort study using Medicare claims from May 2018 to December 2020, analyzing data between August and December 2023. The study included Medicare beneficiaries aged 18 or older with migraine who initiated either anti-CGRP mAbs or onabotulinumtoxinA. Those with a history of myocardial infarction, stroke, cluster headache, cancer, or hospice care were excluded. The researchers compared time to the first myocardial infarction or stroke, with secondary outcomes including hypertensive crisis, peripheral revascularization, and Raynaud phenomenon using Cox proportional hazards models.

The following were the key findings of the study:

• Among 266,848 eligible patients with migraine, 5,153 initiated anti-CGRP mAbs (mean age 57.8 years; 83.6% female) and 4,000 initiated onabotulinumtoxinA (mean age 61.9 years; 83.8% female).
• Anti-CGRP mAbs use was not associated with an increased risk of composite cardiovascular disease events (adjusted hazard ratio [aHR], 0.88) compared to onabotulinumtoxinA.
• There was no increased risk for hypertensive crisis (aHR, 0.46), peripheral revascularization (aHR, 1.50), or Raynaud phenomenon (aHR, 0.75) with anti-CGRP mAbs.
• Subgroup analyses by age group and the presence of established non-MI or stroke CVD yielded similar findings.

This sequential cohort study indicates that Medicare beneficiaries with migraine who used anti-CGRP mAbs did not experience increased cardiovascular risks compared to those using onabotulinumtoxinA. These findings were consistent across different subgroups, including individuals older than 65 and those with existing cardiovascular conditions.

"The study highlights the need for postapproval observational studies using real-world data, as clinical trials often involve populations with fewer cardiovascular concerns. Long-term follow-up in broader populations is essential to fully understand the safety profile of anti-CGRP mAbs. Future research should focus on assessing their long-term safety in larger samples with updated data," the researchers concluded.

Reference:

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