Effects of anti-calcitonin gene-related peptide medications on blood pressure in people with migraine: Review of FDA submission packages
Pratheeshan Sabeshan, Anthony Rodgers, Faraidoon HaghdoostBackground
Several monoclonal antibodies (mAbs) and small molecule antagonists (gepants) targeting calcitonin gene-related peptide (CGRP) effectively prevent migraine. However, some concerns have been raised about a possible increase in blood pressure (BP). As BP outcomes were not routinely included in published trial reports, we evaluated regulatory submission packages to better understand the cardiovascular safety of these drugs.
Methods
We reviewed publicly available U.S. Food and Drug Administration (FDA) clinical trial data for approved anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) and gepants (rimegepant, ubrogepant, zavegepant). The primary outcome was the risk of elevated BP, defined as systolic BP (SBP) ≥ 140 mmHg or diastolic BP (DBP) ≥ 90 mmHg, with SBP and DBP analysed as separate rather than composite outcomes, compared to placebo. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a random-effects model to pool the data for each drug class. This review was conducted and reported in accordance with the PRISMA guidelines.
Results
Twenty randomised controlled trials were included, comprising 18,886 participants with an average follow-up of 12 weeks. Monoclonal antibodies showed no significant effect on SBP ≥140 mmHg (OR 1.0; 95% CI: 0.9–1.1) or DBP ≥90 mmHg (OR 0.9; 95% CI: 0.8–1.2) compared to placebo. Similarly, gepants showed no significant changes in SBP ≥140 mmHg (OR 1.0; 95% CI: 0.8–1.3) or DBP ≥90 mmHg (OR 1.1; 95% CI: 0.9–1.3). In addition, overall reviewer comments in the FDA documents indicate that no consistent or clinically significant changes in systolic or diastolic blood pressure were observed with CGRP-targeting therapies compared to placebo. Rare hypertensive events were reported across drug classes, typically in patients with prior hypertension or concomitant medications. A small dose-dependent increase in the number of patients with a ≥ 10 mmHg rise in DBP was noted for erenumab (AIMOVIG), the only drug for which the FDA explicitly suggested caution regarding high BP.
Conclusion
CGRP-targeting therapies were not associated with overall BP increases, but agent-specific signals warrant caution in patients with cardiovascular risk. BP monitoring may be prudent, and longer-term studies are needed to fully characterise safety.