Three popular CGRP-targeting migraine drugs reduce the force of heart contractions in isolated human atrial tissue at therapeutic concentrations, raising questions about cardiac effects of long-term CGRP blockade.
Therapeutic concentrationsAll three anti-migraine CGRP drugs reduced heart contraction force at the same drug levels found in patients' bloodstreams
What the researchers found
Three anti-migraine drugs that target the CGRP pathway — ubrogepant, erenumab, and eptinezumab — also reduce the force of heart contraction in isolated human atrial tissue at therapeutic concentrations. CGRP (calcitonin gene-related peptide), a key migraine peptide, also increases heart contraction force in human atrial tissue at nanomolar concentrations. All three anti-migraine drugs blocked this cardiac effect of CGRP, both when applied before and after CGRP.
The finding raises an important safety question: since CGRP plays a role in heart function, do anti-migraine drugs that block CGRP also affect the heart in living patients?
Why it matters
Millions of people take CGRP-targeting migraine drugs (like Aimovig/erenumab, Vyepti/eptinezumab, and Ubrelvy/ubrogepant). CGRP is present not just in the brain but in the heart, where it affects contraction force. This study is the first to show that therapeutic concentrations of these migraine drugs block CGRP's cardiac effects in human atrial tissue — raising questions about potential cardiovascular consequences of long-term CGRP inhibition.
The numbers in context
CGRP: 1-100 nM range · Ubrogepant: 1 nM · Erenumab: 2 nM · Eptinezumab: 6 nM · All reduced force of contraction · Human atrial preparations from open-heart surgery patients
How the study worked
Ex vivo study using isolated, electrically driven human atrial tissue preparations obtained from adult patients during open-heart surgery. CGRP was applied at increasing concentrations (1-100 nM) to measure its effect on force of contraction. Three anti-migraine drugs were then tested for their ability to block CGRP's cardiac effects, both as pre-treatment and as post-treatment. The PDE III inhibitor cilostamide was used to enhance CGRP's effects in some experiments.
Who was studied
Human atrial tissue preparations from adult patients undergoing open-heart surgery (ex vivo study)
What this study cannot tell us
Isolated atrial tissue in a dish does not replicate the full complexity of a beating heart in a living person — compensatory mechanisms, autonomic nervous system regulation, and drug metabolism are absent. The tissue came from cardiac surgery patients who may not represent the typical migraine patient population. Whether reduced atrial contraction force at these concentrations has any clinical significance in living patients remains unknown.
How to read the evidence
This is an ex vivo pharmacological study using isolated human heart tissue. It provides important mechanistic data but cannot determine clinical significance. The gap between tissue-level effects and patient-level outcomes is substantial.
When this study was published
Published in 2025. This is very current research addressing an increasingly important question as CGRP-targeting therapies become more widely and chronically used for migraine prevention.
The bigger picture
CGRP-targeting therapies revolutionized migraine treatment and are now used by millions globally. But CGRP has roles throughout the body — in blood vessels, the heart, the gut, and wound healing. This study adds to growing questions about the systemic consequences of chronically blocking a peptide that does much more than cause headaches. The cardiovascular safety profile of long-term CGRP inhibition is an active area of research and post-market surveillance.
Questions still open
- Do patients on long-term CGRP-targeting migraine drugs show any measurable changes in cardiac function or cardiovascular outcomes?
- Is the reduced atrial contraction force clinically significant, or do compensatory mechanisms in the living heart fully offset it?
- Should patients with pre-existing heart conditions be monitored more carefully when starting CGRP-blocking migraine therapies?
Common questions
Should I worry about my heart if I take a CGRP migraine drug?
Why is CGRP in the heart if it causes migraines?
Read the original research
Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.
Naunyn-Schmiedeberg's archives of pharmacology, 398(9), 11909-11918
Citation
Neumann, Joachim; Hofmann, Britt; Gergs, Ulrich. (2025). Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.. Naunyn-Schmiedeberg's archives of pharmacology, 398(9), 11909-11918. https://doi.org/10.1007/s00210-025-04029-7