Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk

Abstract

Background: Fluticasone furoate/vilanterol (FF/VI) is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma. We compared the safety and efficacy of FF/VI and tiotropium (TIO) in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD).

Methods: This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler(®) for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1) 30%-70% predicted, and CVD or CVD risk. The primary endpoint was change from baseline in 24-hour weighted mean FEV1 on Day 84. Other efficacy endpoints included time to onset of bronchodilation, trough FEV1, other spirometry measures, rescue medication use, symptoms, quality of life (St George's Respiratory Questionnaire-COPD [SGRQ-C]), and health status (COPD Assessment Tests [CAT]) measures. Safety endpoints included cardiovascular monitoring, cortisol excretion, COPD exacerbations, and adverse events, including prespecified drug effects.

Results: Both FF/VI and TIO improved the 24-hour weighted mean FEV1 from baseline after 12 weeks with no significant difference between treatments. Other endpoints favored FF/VI for time to onset of bronchodilation, rescue medication use, dyspnea, SGRQ-C and CAT scores, or favored TIO for change from baseline in forced vital capacity and inspiratory capacity. Pneumonia occurred more frequently in the FF/VI group, and two TIO-treated subjects died following cardiovascular events. Other safety measures were similar between groups, and cardiovascular monitoring did not reveal increased CVD risk.

Conclusion: Both FF/VI and TIO were efficacious in improving lung function in subjects with COPD and comorbid CVD or CVD risk factors, with minor differences in efficacy and safety profiles.

Keywords: COPD; ICS/LABA; anticholinergic; cardiovascular disease; fluticasone furoate/vilanterol; tiotropium.

Figure 1

Patient disposition. Abbreviations: FF/VI, fluticasone furoate/vilanterol (100/25 mcg); TIO, tiotropium (18 mcg).

Figure 2

Box plot of change from baseline in 24-h weighted mean FEV₁ (L). Notes: Box represents the IQR, midline represents the median, + represents the mean, whiskers represent 1.5× IQR, circles represent subjects exceeding 1.5× IQR. P=0.201. Abbreviations: FEV₁, forced expiratory volume in 1 second; FF/VI, fluticasone furoate/vilanterol (100/25 mcg); h, hours; IQR, interquartile range; TIO, tiotropium (18 mcg).

Figure 3

Weekly rescue medication use. Notes: (A) Mean weekly use of albuterol/salmeterol rescue medication in inhalations/day over the 12-week course of the study and (B) mean weekly percentage of rescue-free days over the 12-week course of the study. During Weeks 1–12, the LS mean change difference between groups was (A) −0.37 inhalations (95% CI −0.55 to −0.19) and (B) 9.1% (95% CI 4.0–14.2). Albuterol use was measured as occasions used/day. Abbreviations: CI, confidence interval; FF/VI, fluticasone furoate/vilanterol (100/25 mcg); LS, least squares; TIO, tiotropium (18 mcg).

Figure 4

Least squares mean change from baseline in (A) total SGRQ-C score and (B) total CAT score at Weeks 4, 8, and 12. Notes: The LS mean change difference between groups for Week 4 was (A) −2.25 (95% CI −4.00 to −0.51) and (B) −0.9 (95% CI −1.8 to 0.0), for Week 8 was (A) −2.84 (95% CI −4.70 to −0.99) and (B) −0.7 (95% CI −1.6 to 0.2), and for Week 12 was (A) −1.38 (95% CI −3.38 to 0.62) and (B) −0.4 (95% CI −1.3 to 0.5). The MCID of −4 is indicated by a dotted line. Abbreviations: CAT, COPD Assessment Test; CI, confidence interval; FF/VI, fluticasone furoate/vilanterol (100/25 mcg); LS, least squares; MCID, minimal clinically important difference; SGRQ-C, St George’s Respiratory Questionnaire-COPD; TIO, tiotropium (18 mcg).