Cardiovascular Side Effects of Anti-CGRP Migraine Drugs: European Safety Database Analysis

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.

Sorbara, Emanuela Elisa et al.·BioDrugs : clinical immunotherapeutics·2024·Preliminary Evidencecohort
RPEP-09308CohortPreliminary Evidence2024RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
cohort
Evidence
Preliminary Evidence
Sample
N=Large (EudraVigilance database, 2018-2022)
Participants
Patients reporting adverse events with anti-CGRP monoclonal antibodies in Europe

What This Study 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.

Key Numbers

Data covered July 2018 to December 2022 from the EudraVigilance database, focusing specifically on cardiovascular adverse reactions.

How They Did This

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.

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

  • ?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?

Trust & Context

Key Stat:
12.8% cardiovascular ADRs Nearly 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
Evidence Grade:
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.
Study Age:
Published in 2024, covering data from the first 4.5 years of anti-CGRP antibody market availability in Europe.
Original Title:
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.
Published In:
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 38(2), 275-285 (2024)
Database ID:
RPEP-09308

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Should I be worried about heart problems from my CGRP migraine drug?

Cardiovascular adverse events are uncommon — 9,441 reports out of millions of patients treated. However, if you have pre-existing heart conditions or risk factors, discuss this with your doctor. The specific risk pattern varies by drug: erenumab has a slightly higher hypertension signal, while galcanezumab has been associated with rare cardiac events.

Why would blocking CGRP affect the heart?

CGRP is one of the most potent vasodilators in the body — it relaxes blood vessels and increases blood flow. It also plays protective roles during cardiac stress. Blocking CGRP to prevent migraines may inadvertently reduce these cardiovascular protective effects in some patients, though the absolute risk appears to be small.

Read More on RethinkPeptides

Cite This Study

RPEP-09308·https://rethinkpeptides.com/research/RPEP-09308

APA

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

MLA

Sorbara, Emanuela Elisa, et al. "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, 2024. https://doi.org/10.1007/s40259-024-00651-8

RethinkPeptides

RethinkPeptides Research Database. "Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gen..." RPEP-09308. Retrieved from https://rethinkpeptides.com/research/sorbara-2024-cardiovascular-adverse-drug-reactions

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.