A Randomized, Double‐Blind, Placebo‐Controlled Study to Evaluate the Effect of Erenumab on Exercise Time During a Treadmill Test in Patients With Stable Angina

Abstract

ObjectiveTo determine the potential impact of erenumab, a human anti‐calcitonin gene‐related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise‐induced angina, and ST depression in a double‐blind, placebo‐controlled study in patients with stable angina due to documented coronary artery disease.BackgroundThe relative importance of the CGRP receptor pathway during myocardial ischemia has not been established.MethodsAn exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo. The primary endpoint was the change from baseline in exercise duration as measured by TET with a noninferiority margin of −90 seconds. Safety follow‐up visits occurred through week 12. Eighty‐eight participants were included in the analysis.ResultsLS mean (SE) change in TET was −2.9 [14.8] seconds in the erenumab group and 8.1 [14.4] seconds in placebo; adjusted mean (90% CI) treatment difference was −11.0 (–44.9, 22.9) seconds. The CI lower bound (–44.9 sec) did not reach pre‐defined non‐inferiority margin of −90 seconds, demonstrating that TET change from baseline in the erenumab group was non‐inferior to placebo. There was no difference in time to exercise‐induced angina in erenumab and placebo groups (median [90% CI] time of 500 [420, 540] vs 508 [405, 572] seconds; hazard ratio [90% CI]: 1.11 [0.73, 1.69], P = .69) or time to onset of ≥1 mm ST‐segment depression (median [90% CI] time of 407 [380, 443] vs 420 [409,480] seconds; hazard ratio [95% CI]: 1.14 [0.76, 1.69], P = .59). Adverse events were reported by 27% and 32% of patients in erenumab and placebo groups.ConclusionsErenumab did not adversely affect exercise time in a high cardiovascular risk population of patients, supporting that inhibition of the canonical CGRP receptor does not worsen myocardial ischemia.

History and Review of anti‐Calcitonin Gene‐Related Peptide (CGRP) Therapies: From Translational Research to Treatment

“…The primary endpoint was the change from baseline in exercise duration as measured by the total exercise time. The authors stated that “the total exercise time change from baseline in the erenumab group was non‐inferior to that observed in the placebo group, as the lower bound of the confidence interval (−44.9) did not reach the pre‐defined non‐inferiority margin of −90 seconds, supporting the hypothesis that erenumab does not substantially decrease exercise duration.”…”

Novel Medications for the Treatment of Migraine

“…69,70 Patients receiving 70 mg every 4 weeks had significant reduction in MDD at week 64, with 65% of patients achieving ≥50% reduction and 26% achieving 100% reduction. Interim analysis of a 5-year open label extension study of erenumab provides further efficacy and safety information.…”

“…69,70 Patients receiving 70 mg every 4 weeks had significant reduction in MDD at week 64, with 65% of patients achieving ≥50% reduction and 26% achieving 100% reduction. 70 Fremanezumab.-Fremanezumab is a humanized mAb that binds the CGRP ligand, preventing its binding with the receptor. No dose-dependent AEs were observed, and there was no increase in cardiovascular events or changes in blood pressure or heart rate.…”

Triptans for Migraine Patients With Vascular Risks: New Insights, New Options

“…79 Neuromodulation approaches and gepants could be used without concern regarding the risk of inducing medication overuse headache, as both potentially may exert a preventive effect if used frequently. 83 In summary, clinicians treating migraine still face significant challenges that involve the vascular risks associated with migraine, abortive therapies for migraine and the triptans in particular. 47 As CGRP does play a role in vasoregulation, especially in sub-ischemic settings, one plausibly could theorize that a patient with vascular risk factors using a triptan may be more at risk for cardiac or cerebral ischemia with an anti-CGRP MAB than without.…”