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.

OBJECTIVE

To 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.

BACKGROUND

The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established.

METHODS

An 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.

RESULTS

LS 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.

CONCLUSIONS

Erenumab 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.