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 Phas...
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doaj-bc54e68176db4ca5a7f7fcc01003961a2020-11-25T03:21:40ZengBMCRespiratory Research1465-993X2020-06-0121111210.1186/s12931-020-01398-wSingle-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 trialNicola C. Day0Subramanya Kumar1Gerard Criner2Mark Dransfield3David M. G. Halpin4MeiLan K. Han5C. Elaine Jones6Morrys C. Kaisermann7Sally Kilbride8Peter Lange9David A. Lomas10Neil Martin11Fernando J. Martinez12Dave Singh13Robert Wise14David A. Lipson15GlaxoSmithKlineGlaxoSmithKlineLewis Katz School of Medicine at Temple UniversityDivision of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at BirminghamUniversity of Exeter Medical School, College of Medicine and HealthUniversity of Michigan, Pulmonary & Critical CareGlaxoSmithKlineGlaxoSmithKlineGlaxoSmithKlineDepartment of Public Health, Section of Epidemiology, University of CopenhagenUCL Respiratory, University College LondonGlaxoSmithKlineNew York-Presbyterian Weill Cornell Medical CenterUniversity of Manchester, Manchester University NHS Foundation TrustDivision of Pulmonary and Critical Care Medicine, Johns Hopkins MedicineGlaxoSmithKlineAbstract 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).http://link.springer.com/article/10.1186/s12931-020-01398-wCOPDTriple therapyLAMA/LABAICS/LABACardiovascular safety |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 Respiratory Research COPD Triple therapy LAMA/LABA ICS/LABA Cardiovascular safety |
author_facet |
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 |
author_sort |
Nicola C. Day |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2020-06-01 |
description |
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). |
topic |
COPD Triple therapy LAMA/LABA ICS/LABA Cardiovascular safety |
url |
http://link.springer.com/article/10.1186/s12931-020-01398-w |
work_keys_str_mv |
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