2026 Southeastern Residency Conference

Background  -
Since 2018, calcitonin gene-related peptide (CGRP)–targeting therapies have expanded migraine prevention options. Inhibiting endogenous CGRP may pose risks, as recently noted by the US Food and Drug Administration (FDA) with new safety information and now requiring the risks of worsening hypertension and Raynaud’s phenomenon to be included in the labeling for all CGRP-targeting agents. This project aimed to assess the risk of clinically relevant blood pressure changes and other adverse outcomes associated with long-term CGRP-targeting therapy and to identify baseline risk factors that might guide safer use.

Methods -
This is a retrospective observational longitudinal cohort project for quality improvement. Eligible patients enrolled within the Ralph H. Johnson Veterans Affairs Healthcare System (RHJVAHS) who had an active diagnosis of migraine and a documented prescription for CGRP-targeting therapies for migraine prevention between May 17, 2018 and July 31, 2024 were included. Therapies examined were erenumab, fremanezumab, galcanezumab, atogepant, and rimegepant. A longitudinal logistic model was used to evaluate variables over time, from baseline within 1 year prior to starting to 1 year after initiation of CGRP-targeting treatment with quarterly follow-up.
The primary objective was to determine whether there is a clinically relevant change in median blood pressure, defined as an increase in stage of hypertension, increase in antihypertensive medication dose or additional antihypertensive medication added, or any episode of hypertensive crisis after use of a CGRP-targeting agent long-term for migraine prevention. The secondary objective was to determine whether there is an increased incidence of all cause hospitalizations, ER visits, or new Raynaud’s Syndrome diagnosis after use.

Results –
A total of 490 unique patients (5,188 encounters; mean follow-up 2.6 years) were included. The primary composite outcome was observed in 3,253 (64.7%) encounters. Adjusted mean probabilities for the composite outcome were similar across drug exposures. No agent was associated with significantly increased odds of composite outcome versus erenumab 70 mg. Atogepant showed a non-significant lower risk (OR 0.654, 95% CI 0.414–1.034; p=0.07) while a nonsignificant increased risk was observed for encounters with no CGRP-targeting agent refill, OR 1.33 (95% CI: 0.981-1.810]; p = 0.066.
After adjusting for baseline comorbidities, Black race was associated with significantly lower odds of the primary outcome as well as a history of coronary artery disease (CAD) and use of abortive CGRP-targeting therapy. There was no statistically significant association between the primary outcome and the presence of obstructive sleep apnea or chronic kidney disease, however an increasing number of baseline antihypertensive medications was significantly associated with higher odds of the composite outcome.
Secondary analyses revealed 2,728 (54.3%) encounters with hypertension stage progression, but no agent was associated with increased risk compared to erenumab 70 mg. Rimegepant 75 mg was associated with a higher odds ratio (OR 1.852, 95% CI 0.975–3.518; p = 0.06); however, this did not reach statistical significance. Among 564 (11.2%) encounters with escalation of antihypertensive therapy, dose decrease of CGRP therapy was linked to more than a two-fold higher risk of escalation (OR 2.277, 95% CI 1.027–5.046, p=0.043), likely reflecting blood pressure-related medication adjustments. Hypertensive crisis was very rare (n=1). Secondary outcomes occurred infrequently and are not reported here.

Conclusion:
Long-term use of CGRP-targeting therapies in this veteran population was associated with a significant incidence of clinically relevant worsening of hypertension, with nearly 65% of encounters experiencing the composite outcome, driven primarily by progression in hypertension staging. No statistically significant differences in risk were observed between individual CGRP agents and the erenumab 70 mg reference. Numerical higher risk with rimegepant and lower risk with atogepant warrant further study. Ongoing blood pressure monitoring in patients treated with CGRP-targeting drugs remains warranted.