PURPOSE: COPD exacerbations are associated with worse health status, increased hospitalisations and premature death. Existing studies have demonstrated that fluticasone propionate/salmeterol (FSC) significantly reduces exacerbations over 1 year. This study investigated whether FSC could significantly reduce exacerbations over 3 years compared with placebo or either component alone.
METHODS: This was a 3 year, double-blind, placebo controlled multi-center trial of 6112 (intention to treat population) patients with moderate to severe COPD from 42 countries (mean age 65 yrs, 76% males, 44% predicted post-bronchodilator FEV1, 43% current smokers). Patients were randomised to receive FP 500mcg (n=1534), SAL 50mcg (n=1521), FSC 500/50 (n=1533), or placebo (n=1524) bid via Diskus(R). Exacerbations, a secondary outcome in the study, were defined as moderate if they were treated with antibiotics and/or systemic corticosteroids (SCS) and severe if hospitalised.
RESULTS: Over 13,000 exacerbations were recorded in the study. The mean rate of moderate/severe exacerbations per annum was 1.13 (placebo), 0.97 (SAL), 0.93 (FP) and 0.85 (FSC). Greatest reductions in rate of moderate/severe exacerbations were achieved with FSC (25% reduction vs placebo, p<0.001; 12% reduction vs SAL, p=0.002; 9% reduction vs FP, p=0.024). Both components were also significantly more effective than placebo (15% and 18% reduction vs placebo for SAL and FP respectively, both p<0.001). Further, there was a 43% reduction in rate of exacerbations treated with SCS for FSC vs placebo (p<0.001), 29% reduction vs SAL (p<0.001) and 13% vs FP (p=0.017). FSC reduced the rate of severe exacerbations by 17% (p=0.028 vs placebo).
CONCLUSION: In this large world-wide trial, inhaled salmeterol, fluticasone propionate and fluticasone propionate/salmeterol significantly reduced moderate/severe exacerbations over 3 years compared with placebo. Significantly greater reductions were seen with FSC compared with either component alone, especially for exacerbations requiring SCS.
CLINICAL IMPLICATIONS: FSC provides an important reduction in the burden of COPD exacerbations. This has significant implications for patients and healthcare systems.
DISCLOSURE: Bartolome Celli, Grant monies (from industry related sources) This study is funded by a grant from GlaxoSmithKline. Departments of BC, CJ, PC, GF, JV, receive funding from GlaxoSmithKline for specific research projects; Employee JA and JY are employees of GlaxoSmithKline; Consultant fee, speaker bureau, advisory committee, etc. PJ, PC, BC, GF, CJ, JV and NP have been speakers and consultants for companies including GSK, Pfizer, AstraZeneca, Boehringer Ingelheim; Other JV’s wife was until 2004 a GSK employee; Product/procedure/technique that is considered research and is NOT yet approved for any purpose, FSC 500/50 dose currently unlicensed for COPD in U.S.