Mortality Risk and Serious Cardiopulmonary Events in Moderate-to-Severe COPD: Post Hoc Analysis of the IMPACT Trial

J Michael Wells; Gerard J Criner; David M G Halpin; MeiLan K Han; Renu Jain; Peter Lange; David A Lipson; Fernando J Martinez; Dawn Midwinter; Dave Singh; Robert A Wise

doi:10.15326/jcopdf.2022.0332

Mortality Risk and Serious Cardiopulmonary Events in Moderate-to-Severe COPD: Post Hoc Analysis of the IMPACT Trial

Chronic Obstr Pulm Dis. 2023 Jan 25;10(1):33-45. doi: 10.15326/jcopdf.2022.0332.

Authors

J Michael Wells¹, Gerard J Criner², David M G Halpin³, MeiLan K Han⁴, Renu Jain⁵, Peter Lange^{6

7}, David A Lipson^{8

9}, Fernando J Martinez¹⁰, Dawn Midwinter¹¹, Dave Singh¹², Robert A Wise¹³

Affiliations

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama, United States.
² Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States.
³ University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
⁴ Pulmonary and Critical Care, University of Michigan, Ann Arbor, Michigan, United States.
⁵ GSK, Research Triangle Park, North Carolina, United States.
⁶ Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
⁷ Pulmonary Section, Medical Department, Herlev-Gentofte Hospital, Herlev, Denmark.
⁸ GSK, Collegeville, Pennsylvania, United States.
⁹ Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
¹⁰ New York-Presbyterian Weill Cornell Medical Center, New York, New York, United States.
¹¹ GSK, Brentford, United Kingdom.
¹² Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester University NHS Foundation Hospital Trust, Manchester, United Kingdom.
¹³ Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

Abstract

Background: In the InforMing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler fluticasone furoate (FF) /umeclidinium (UMEC) /vilanterol (VI) significantly reduced severe exacerbation rates and all-cause mortality (ACM) risk versus UMEC/VI among patients with chronic obstructive pulmonary disease (COPD). This post hoc analysis aimed to define the risk of ACM during and following a moderate/severe exacerbation, and further determine the benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI using a cardiopulmonary composite adverse event (AE) endpoint.

Methods: The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25mcg, FF/VI 100/25mcg, or UMEC/VI 62.5/25mcg. Post hoc endpoints included the risk of ACM during, 1-90 and 91-365 days post moderate or severe exacerbation and time-to-first cardiopulmonary composite event.

Results: Of the 10,355 patients included, 5034 (49%) experienced moderate/severe exacerbations. Risk of ACM was significantly increased during a severe exacerbation event compared with baseline (hazard ratio [HR]: 41.22 [95% confidence interval (CI) 26.49-64.15]; p<0.001) but not significantly different at 1-90 days post-severe exacerbation (HR: 2.13 [95% CI: 0.86-5.29]; p=0.102). Moderate exacerbations did not significantly increase the risk of ACM during or after an exacerbation. Cardiopulmonary composite events occurred in 647 (16%), 636 (15%), and 356 (17%) patients receiving FF/UMEC/VI, FF/VI, and UMEC/VI, respectively; FF/UMEC/VI significantly reduced cardiopulmonary composite event risk versus UMEC/VI by 16.5% (95% CI: 5.0-26.7; p=0.006).

Conclusion: Results confirm a substantial mortality risk during severe exacerbations, and an underlying CV risk. FF/UMEC/VI significantly reduced the risk of a composite cardiopulmonary AE versus UMEC/VI.

Keywords: cardiovascular diseases; chronic obstructive; pneumonia; pulmonary disease; respiratory therapy.

Abstract

Grants and funding