Cardiovascular Risk of CGRP Therapies for Migraine
CGRP-targeted monoclonal antibodies do NOT carry a "moderate risk" for cardiovascular disease in most patients, but they should be used with caution in those with established cardiovascular disease, particularly small vessel disease, and erenumab specifically has been associated with hypertension risk. 1, 2
Current Evidence on Cardiovascular Safety
Overall Safety Profile
- Clinical trials have not demonstrated significant cardiovascular safety concerns with CGRP monoclonal antibodies, with adverse event profiles generally mild and discontinuation rates low 1, 3
- At present, there is insufficient evidence to contraindicate gepants and CGRP mAbs in patients with cardiovascular disease including stroke or myocardial infarction 4
- No direct cardiovascular contraindications exist for most CGRP-mAbs, though caution is advised in patients with coronary heart disease 1
Agent-Specific Considerations
- Erenumab carries unique hypertension risk: The FDA reports that erenumab has been associated with development or worsening of hypertension in post-marketing studies, requiring monitoring during treatment 1, 2, 4
- Fremanezumab may be safer for cardiovascular concerns: It has not been associated with hypertension in post-marketing studies, unlike erenumab, making it a potentially safer option for patients with cardiovascular concerns 1
Theoretical vs. Clinical Risk
The Theoretical Concern
- CGRP acts as a vasodilatory safeguard during cerebral and cardiac ischemia, raising theoretical concerns that CGRP blockade could transform transient mild ischemic events into full-blown infarcts 5
- Vasodilation may be an important CGRP-mediated mechanism during ischemia, especially in patients with small vessel disease 4
Clinical Reality
- Despite theoretical concerns from 2016, subsequent clinical trials through 2023 have not confirmed these cardiovascular risks in practice 5, 3, 4
- Neither cardiovascular nor immunological safety concerns have emerged from phase III clinical trials 3
Clinical Recommendations
When to Use with Caution
- Use caution in patients with small vessel disease, where CGRP-mediated vasodilation may be particularly important during ischemic events 4
- Monitor blood pressure with erenumab due to its association with hypertension development or worsening 1, 2
- Ensure patients with any cardiovascular history are aware of the limitations of current long-term safety data 4
Preferred Agents for Cardiovascular Concerns
- Consider fremanezumab, galcanezumab, or eptinezumab (which bind CGRP peptide directly) over erenumab (which blocks the receptor) in patients with cardiovascular concerns 1, 6
- Fremanezumab specifically has not shown hypertension associations in post-marketing surveillance 1
Common Pitfalls to Avoid
- Do not automatically exclude patients with cardiovascular disease from CGRP therapy—the evidence does not support absolute contraindication, only cautious use 4
- Do not fail to monitor blood pressure when prescribing erenumab, as this is the one agent with documented hypertension risk 1, 2
- Do not ignore the superior tolerability profile compared to conventional preventives like topiramate, which has much higher discontinuation rates due to adverse events 1, 7