Effect Of Tiotropium And Salmeterol In COPD Patients With Low Or High Risk Of Exacerbations: A Post-Hoc Analysis From The Prevention of Exacerbations with Tiotropium in COPD (POET-COPD®) Trial

Rationale: A history of past exacerbations (EX) is a predictor of future events in COPD patients (PT). The latest GOLD strategy divides PT into low (≤2 EX, no severe EX) and high (≥2 or ≥1 severe EX) risk categories. The current study explores the effect of tiotropium (T) and salmeterol (S) on EX in PT with a low (LR) or high risk (HR) of an EX during a 1-yr treatment period in the POET-COPD® trial (N= 3456), in which PT had a history of at least one EX within the previous yr.

Methods: We conducted a post-hoc analysis of the POET-COPD® database. PT were classified as having a LR of EX (infrequent exacerbators: ≤1 EX and no COPD-related hospitalization(s) in the preceding yr) or having a HR of EX (frequent exacerbators: ≥2 EX [courses of oral steroids/antibiotics] or ≥1 COPD-related hospitalization(s) in the preceding yr, based on the GOLD 2013 definition).

Results:

CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; RR, rate ratio
	Time to first COPD exacerbation
	Tiotropium		Salmeterol		Tiotropium vs salmeterol
	N	# events	N	# events	HR (95% CI)	P-value
Low-risk subgroup	1324	375	1286	402	0.89 (0.77, 1.02)	0.1046
High-risk subgroup	2132	824	2152	933	0.84 (0.76, 0.92)	0.0002
	Number of COPD exacerbations during study
	Tiotropium adjusted rate of events per patient year		Salmeterol adjusted rate of events per patient year		Tiotropium vs salmeterol RR
	N	Mean (95% CI)	N	Mean (95% CI)	Mean (95% CI)	P-value
Low-risk subgroup	1324	0.48 (0.43, 0.54)	1286	0.54 (0.48, 0.60)	0.89 (0.76, 1.05)	0.1763
High-risk subgroup	2132	0.76 (0.71, 0.82)	2152	0.85 (0.79, 0.91)	0.90 (0.81, 0.99)	0.0383

Additionally, comparing PT at LR vs HR for EX before and after 1-yr's treatment with either T or S showed that treatment resulted in a shift in this ratio (low/high EX risk) from 0.62 to 4.98 and from 0.60 to 4.25 for treatment with T and S, respectively. After treatment, the risk of remaining in the HR exacerbator subgroup was statistically lower with T compared with S (rate ratio: 0.89; 95% confidence interval [CI]: 0.80, 1.00; P= 0.0478). Although the LR subgroup is relatively stable, the risk of moving from the LR subgroup into the HR subgroup was numerically lower with T compared with S (RR: 0.87; 95% CI: 0.71, 1.07; P= 0.1968).

Conclusions: In this analysis, it was shown that both T and S influenced the ratio for low risk/high risk for exacerbations in a favorable manner, having a stabilizing effect on the disease. Furthermore it confirms the higher efficacy of T compared with S in prolonging the time to first exacerbation and reducing the number of exacerbations in PT considered to be at low and high risk of exacerbations.

Funded by Boehringer Ingelheim.

Presented at the ATS congress meeting 2014