Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial.

Abstract

BACKGROUND:

This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy.

METHODS:

IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death.

RESULTS:

Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments.

CONCLUSIONS:

In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10-11% and 1-3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI.

TRIAL REGISTRATION:

NCT02164513 (GSK study number CTT116855).

• Authors: Nicola C Day, Subramanya Kumar, Gerard Criner, Mark Dransfield, David M G Halpin, MeiLan K Han, C Elaine Jones, Morrys C Kaisermann, Sally Kilbride, Peter Lange, David A Lomas, Neil Martin, Fernando J Martinez, Dave Singh, Robert Wise, David A Lipson
• Journal: Respiratory research (Respir Res) Vol. 21 Issue 1 Pg. 139 (Jun 05 2020) ISSN: 1465-993X [Electronic] England
• PMID: 32503599 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Androstadienes
• Benzyl Alcohols
• Chlorobenzenes
• Drug Combinations
• GSK573719
• Quinuclidines
• vilanterol
• fluticasone furoate

Topics

• Aged
• Androstadienes (administration & dosage, adverse effects)
• Benzyl Alcohols (administration & dosage, adverse effects)
• Cardiovascular Diseases (chemically induced, diagnosis)
• Chlorobenzenes (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Combinations
• Female
• Humans
• Male
• Middle Aged
• Nebulizers and Vaporizers (trends)
• Pulmonary Disease, Chronic Obstructive (diagnosis, drug therapy)
• Quinuclidines (administration & dosage, adverse effects)