Reduction in All-Cause Mortality with Fluticasone Furoate/Umeclidinium/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Rationale: The IMPACT trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with COPD at risk of future exacerbations. 574 patients were censored from the original analysis due to incomplete vital status information. Objective: Report ACM and impact of stepping down therapy, following collection of additional vital status data. Methods: Patients were randomized 2:2:1 to FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg or UMEC/VI 62.5/25µg following a run-in on their COPD therapies. Time to ACM was prespecified. Additional vital status data collection and subsequent analyses were performed post hoc. Measurements and Main Results: We report vital status data for 99.6% of the intention-to-treat population (n=10,355), documenting 98(2.36%) deaths on FF/UMEC/VI, 109(2.64%) on FF/VI, and 66(3.19%) on UMEC/VI. For FF/UMEC/VI, the hazard ratio for death was 0.72 (95%CI: 0.53,0.99;P=0.042) versus UMEC/VI and 0.89 (95%CI: 0.67,1.16;P=0.387) versus FF/VI. Independent adjudication confirmed lower rates of cardiovascular and respiratory death, and death associated with the patient’s COPD. Conclusions: In this secondary analysis of an efficacy outcome from the IMPACT trial, once-daily single-inhaler FF/UMEC/VI triple therapy reduced the risk of ACM versus UMEC/VI in patients with symptomatic COPD and a history of exacerbations. Funding: GSK(CTT116855/NCT02164513). This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).