Cardiovascular Safety of Revefenacin as COPD Treatment Examined

A total of 26 major cardiovascular adverse events occurred in 1 of the studies, but only 1 was related to revefenacin.
A total of 26 major cardiovascular adverse events occurred in 1 of the studies, but only 1 was related to revefenacin.
This article is part of MPR's coverage of CHEST 2018 meeting, taking place in San Antonio, TX. Our on-site staff will be reporting on the latest breaking research and clinical advances in infectious diseases. Check back regularly for highlights from CHEST 2018 meeting.

SAN ANTONIO — Once-daily revefenacin does not prolong QT interval and offers an acceptable 1-year cardiovascular safety profile for treatment of chronic obstructive pulmonary disease (COPD), according to a study presented at the CHEST Annual Meeting, held October 6-10, 2018, in San Antonio, Texas.

Because cardiovascular disease is common in people with COPD, researchers analyzed cardiovascular safety data from 3 randomized trials of revefenacin as well as data from a thorough QT study in healthy individuals.

Healthy individuals received once-daily therapeutic (175μg) and supratherapeutic (700μg) revefenacin doses in a phase 1, placebo-controlled study (n=48). The researchers assessed the association between daily revefenacin treatment at 88μg and 175 μg with cardiovascular safety in patients with moderate to very severe COPD in 2 phase 3 trials of 12 weeks' duration (n=619 and n=611). An active-controlled phase 3 safety trial of 52 weeks' duration was also included in the analysis (n=699). Prespecified major cardiovascular adverse events (MACE) were evaluated in all patients with COPD receiving treatment.

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There was no clinically meaningful effect of single-dose revefenacin on cardiac repolarization in healthy individuals. Additionally, in the 52-week trial, the investigators observed no changes in 12-lead electrocardiographic recordings associated with daily doses of revefenacin 88μg and 175μg in patients with COPD. Additionally, the incidences of prolonged cardiac repolarization in the 52-week trial were similar between the revefenacin 175μg (7.7%) and tiotropium (7.3%) groups.

Treatment with revefenacin 175μg and 700μg in single doses did not result in any cardiovascular-related treatment-emergent adverse events in healthy individuals. Following adjudication by a clinical end point committee, the researchers identified 4 MACE in the 12-week study, with 2, 1, and 1 MACE in the 88-μg revefenacin, 175-μg revefenacin, and placebo groups, respectively. In addition, a total of 26 MACE were recorded in the 52-week trial, all of which were reported in the treatment groups. Of these, only 1 (atrial fibrillation) was thought to be related to revefenacin.

Disclosures: Several researchers report financial relationships with pharmaceutical companies.

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Reference

Donohue J, Feldman G, Sethi S, et al. Cardiovascular safety of revefenacin for nebulization: a review of randomized controlled trial data. Presented at: CHEST Annual Meeting 2018; October 6-10, 2018; San Antonio, TX.