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

Abstract

Rationale: The IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial demonstrated a significant reduction in all-cause mortality (ACM) risk with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) at risk of future exacerbations. Five hundred seventy-four patients were censored in the original analysis owing to incomplete vital status information.Objectives: 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 100/62.5/25 mg, FF/VI 100/25 mg, or UMEC/VI 62.5/25 mg 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% confidence interval, 0.53-0.99; P = 0.042) versus UMEC/VI and 0.89 (95% confidence interval, 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.

Implications of Managing Chronic Obstructive Pulmonary Disease in Cardiovascular Diseases

“…Fluticasone/vilanterol/umeclidinium has also been shown to reduce allcause mortality with lower rates of cardiovascular and respiratory deaths. 78…”

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

“…The greater reduction in the rate and risk of exacerbations observed with FF/UMEC/VI compared with either dual therapy in the IMPACT trial [22] may therefore be expected to reduce the risk of CV mortality. The IMPACT trial demonstrated a significant 28% reduction in on−/off-treatment all-cause mortality with FF/UMEC/VI versus UMEC/VI and a non-statistically significant reduction of 11% versus FF/VI, although CV mortality has not been specifically assessed [35,36]. As the current analysis is focused on all CVAESI and only includes on-treatment events, it would be of interest to further explore the relationship between CV events, COPD exacerbations, and mortality in IMPACT in future analyses.…”

Fixed Triple Therapy in Chronic Obstructive Pulmonary Disease and Survival. Living Better, Longer, or Both?

“…Let's Rise to the Challenge Acute exacerbations of chronic obstructive pulmonary disease (COPD) worsen the symptoms, airflow obstruction, functional disability, and quality of life, and increase mortality risk for those with the disease (1), particularly among those requiring hospitalization. Recovery from COPD exacerbations is often slow; symptoms may take months to resolve and hospital readmissions are common (1,2). Pulmonary rehabilitation (PR) is an essential component of the integrated care of individuals with COPD and other chronic respiratory diseases (3) and is effective in fostering patients' recovery after hospitalization for COPD exacerbation (4,5).…”

“…Pulmonary rehabilitation (PR) is an essential component of the integrated care of individuals with COPD and other chronic respiratory diseases (3) and is effective in fostering patients' recovery after hospitalization for COPD exacerbation (4,5). When delivered within 4 weeks of exacerbation, it improves exercise capacity, symptoms, and quality of life and reduces hospital readmission risk (4); it is recommended in disease management guidelines (1,6). Studies have also shown a survival advantage related to postexacerbation PR (4, 7).…”

“…In this issue of the Journal, Lipson and colleagues (pp. 1508-1516) report findings from a post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (1). The trial was enriched for exacerbators, and the primary outcome was the annual rate of on-treatment moderate and severe exacerbations comparing a fixed combination of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) with fixed combinations of UMEC/VI and FF/VI.…”