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

Christophe Depre, Lubomir Antalik, Amaal Starling, Michael Koren, Osaro Eisele, Robert A. Lenz, Daniel D. Mikol

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)715-723
Number of pages9
JournalHeadache
Volume58
Issue number5
DOIs
StatePublished - May 1 2018

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Stable Angina
Exercise Test
Placebos
Exercise
Calcitonin Gene-Related Peptide Receptors
Myocardial Ischemia
Coronary Artery Disease
Monoclonal Antibodies
Safety

Keywords

  • calcitonin gene-related peptide
  • cardiovascular
  • clinical trial
  • safety

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

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. / Depre, Christophe; Antalik, Lubomir; Starling, Amaal; Koren, Michael; Eisele, Osaro; Lenz, Robert A.; Mikol, Daniel D.

In: Headache, Vol. 58, No. 5, 01.05.2018, p. 715-723.

Research output: Contribution to journalArticle

Depre, Christophe ; Antalik, Lubomir ; Starling, Amaal ; Koren, Michael ; Eisele, Osaro ; Lenz, Robert A. ; Mikol, Daniel D. / 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. In: Headache. 2018 ; Vol. 58, No. 5. pp. 715-723.
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abstract = "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.",
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AU - Depre, Christophe

AU - Antalik, Lubomir

AU - Starling, Amaal

AU - Koren, Michael

AU - Eisele, Osaro

AU - Lenz, Robert A.

AU - Mikol, Daniel D.

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N2 - 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.

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