Analysis of 9,441 European adverse event reports found that anti-CGRP migraine antibodies carry cardiovascular risks including hypertension (erenumab), atrial fibrillation and heart attack (galcanezumab), and blood clots (fremanezumab) — some not listed on drug labels.
12.8% cardiovascular ADRsNearly 1 in 8 adverse event reports for anti-CGRP migraine antibodies involved cardiovascular effects, with 67.5% classified as serious — and several specific risks not listed on official drug labels
What the researchers found
Among 9,441 ICSRs, 12.8% involved cardiovascular adverse events (1,205 reports, 1,599 CV ADRs). 67.5% of CV ADRs were serious. Disproportionate reporting: erenumab — hypertension (ROR 1.45); galcanezumab — atrial fibrillation (ROR 2.36), myocardial infarction (ROR 2.21); fremanezumab — deep vein thrombosis (ROR 3.86), pallor (ROR 5.00), palpitations (ROR 1.48). Several findings not in official drug labels.
Why it matters
CGRP has known cardiovascular functions including blood vessel dilation, so blocking it could theoretically affect heart and blood vessel function. These pharmacovigilance data provide the first large-scale real-world evidence of drug-specific cardiovascular risk patterns that differ across the anti-CGRP antibodies — information critical for prescribing decisions, especially in migraine patients with pre-existing cardiovascular conditions.
The numbers in context
Data covered July 2018 to December 2022 from the EudraVigilance database, focusing specifically on cardiovascular adverse reactions.
How the study worked
Pharmacovigilance disproportionality analysis of the EudraVigilance database (July 2018–December 2022). Reporting odds ratios (ROR) with 95% CI compared CV adverse event rates for each anti-CGRP mAb against all other monoclonal antibodies. Case-by-case analysis of serious CV reports examined seriousness, age, sex, and concomitant medications.
Who was studied
Patients reporting adverse events with anti-CGRP monoclonal antibodies in Europe
What this study cannot tell us
Pharmacovigilance data has inherent biases: underreporting, reporting biases (newer drugs get more attention), inability to establish causation, and no denominator (total prescriptions) to calculate incidence. Erenumab's dominance (58.9% of reports) reflects its earlier market entry. The comparator group (all other mAbs) may not be ideal since different mAbs treat different diseases.
How to read the evidence
Moderate evidence from a large pharmacovigilance database analysis. While spontaneous reporting data cannot establish causation, the large sample size and consistent signal patterns across specific drugs provide meaningful safety information.
When this study was published
Published in 2024, covering data from the first 4.5 years of anti-CGRP antibody market availability in Europe.
The bigger picture
CGRP is a vasodilator peptide, and blocking it was always expected to carry some cardiovascular theoretical risk. Now with millions of patients using these drugs, real-world safety signals are emerging that differ between the four available antibodies. This has implications for personalized prescribing — the choice of anti-CGRP drug may need to consider a patient's specific cardiovascular risk factors.
Questions still open
- Should patients with pre-existing cardiovascular conditions be steered toward specific anti-CGRP antibodies based on these differential safety signals?
- Do the cardiovascular adverse events reflect true CGRP-blocking effects, or are they confounded by migraine itself being a cardiovascular risk factor?
Common questions
Should I be worried about heart problems from my CGRP migraine drug?
Why would blocking CGRP affect the heart?
Read the original research
Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies for Migraine Prevention: An Analysis from the European Spontaneous Adverse Event Reporting System.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 38(2), 275-285
Citation
Sorbara, Emanuela Elisa; Barbieri, Maria Antonietta; Russo, Giulia; Cicala, Giuseppe; Spina, Edoardo. (2024). Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies for Migraine Prevention: An Analysis from the European Spontaneous Adverse Event Reporting System.. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 38(2), 275-285. https://doi.org/10.1007/s40259-024-00651-8