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

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

“…AESIs were pre-specified AEs that may be associated with the used of inhaled steroids, LAMA or LABA. 17,25…”

Inhaled Corticosteroids and Risk of Cardiovascular Disease in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Regression

“…Four studies excluded patients with a history of CVD. 5,[10][11][12] Two studies required patients to have a history of CVD. 12, 13 The remaining studies did not specify inclusion or exclusion criteria around a history of CVD.…”

Chronic obstructive pulmonary disease: moving from symptom relief to mortality reduction

“…Furthermore, other long-term side effects, like metabolic, cardiovascular, and musculoskeletal diseases, in patients with COPD treated with moderate/high-dose ICSs are fairly rare and frequently not different from those observed in non-ICS-treated patients. 41 , 42 …”

“…Furthermore, other long-term side effects, like metabolic, cardiovascular, and musculoskeletal diseases, in patients with COPD treated with moderate/high-dose ICSs are fairly rare and frequently not different from those observed in non-ICS-treated patients. 41,42 According to the systemic inflammation theory, the activation of proinflammatory mediators in the peripheral circulation, associated with chronic persistent airway inflammation, may lead to negative consequences, both in the cardiovascular system and in other organs and systems. [43][44][45] In support of this theory, C-reactive protein (CRP), proinflammatory cytokines, and endothelium-derived microparticles have been detected in the blood of patients with COPD, increasing with COPD severity.…”