Risk of hypertension after CGRP antagonist treatment in migraine: A systematic review and meta-analysis

This study aimed to systematically summarize and pool the available evidence on the risk of incident hypertension associated with calcitonin gene-related peptide (CGRP)-targeted therapies. CGRP-targeted therapies have emerged as effective preventive treatments for migraine; however, concerns have been raised regarding their potential hypertensive effects. Prior studies have been limited by small sample sizes, inconsistent definitions of hypertension, and incomplete trial inclusion.

We systematically searched MEDLINE, Embase, and ClinicalTrials.gov up to September 25, 2024. We included randomized controlled trials comparing CGRP-targeted therapies with placebo or another intervention arm in adult patients with migraine. The primary outcome was incident hypertension as defined by each individual study. Two reviewers independently assessed risk of bias using the Cochrane Risk of Bias 2 tool and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Eight publications or trial reports, comprising 19 underlying randomized controlled trials, were included. The pooled relative risk (RR) for hypertension with CGRP-targeted therapies versus control was 0.91 (95% confidence interval [CI] 0.58-1.43; I² = 0.0%), indicating no statistically significant increased risk. The certainty of evidence for this outcome was rated as very low. Erenumab showed no significant increase in risk (RR 0.71, 95% CI 0.30-1.70), whereas galcanezumab also showed no statistically significant association (RR 1.14, 95% CI 0.54-2.39).

CGRP-targeted therapies were not associated with a statistically significant increase in hypertension risk in patients with migraine, particularly among relatively healthy populations enrolled in short-term randomized controlled trials. However, the certainty of evidence was very low, and possible variation across agents warrants further study. Longer term comparative studies and real-world observational studies with standardized blood pressure monitoring are needed to confirm these findings and better define hypertension risk in higher risk patient subgroups.