Table 4.

Effect of other therapies on the risk of COPD exacerbation

Treatment [Reference]	Annual exacerbation rate	Comparator	Annual exacerbation rate	Reduction in exacerbations	Exacerbation endpoint	Patient population
						Exacerbation entry criteria (No./year)	FEV1 % predicted
Macrolide antibiotics
Azithromycin [107]	1.94	Placebo	3.22	42 %	Primary (any)	≥3	NA
Azithromycin [108]	1.48	Placebo	1.83	27 %	Primary (moderate or severe)	≥1 severe	<70 % (post-BD)
Azithromycin [142]	2.8	Baseline	6.8	59 %	Moderate or severe	≥4	<50 % (post-BD)
Erythromycin [143]	1	Placebo	2	35 %	Primary (moderate or severe)	NA	30–70 %
Mucolytics
Carbocysteine [144]	1.01	Placebo	1.35	25 %	Primary (any)	≥2 in 2 years	25–79 %
N-acetylcysteine (high dose) [113]	1.16	Placebo	1.49	22 %	Primary (any)	NA	30–70 %
N-acetylcysteine [114]	0.96	Placebo	1.71	43.9 %	Secondary	≥1	Not stated
N-acetylcysteine [131]	1.00	Placebo	0.73	NS	Primary	NA	<90 % (post-BD)
N-acetylcysteine [145, 146]	1.25	Placebo	1.29	NS	Primary	≥2 (previous 2 years)	40–70 % (post-BD)
PDE-4 inhibitor
Roflumilast [99]	0.81	Placebo	0.93	NS	Primary (moderate or severe)	≥2 (and chronic cough/sputum)	<50 % (post-BD)
Roflumilast [147]	1.14	Placebo	1.37	16.9 %	Primary (moderate or severe)	≥1	≤50 % (post-BD)
Roflumilast [97]	1.14	Placebo	1.37	17 % (2 studies pooled)	Primary (moderate or severe)	≥1 (and chronic cough/sputum)	<50 % (post-BD)
Roflumilast [148]	0.86	Placebo	0.92	NS	Primary (moderate or severe)	NA	<50 % (post-BD)

Studies identified using PubMed search of key terms and limited to clinical trials published in English language and including at least 100 patients. Results were manually filtered for relevance and additional studies added at the author’s discretion. Reductions in exacerbations vs comparator were statistically significant unless otherwise stated (See Additional file 1 for detailed description of term used in searchs)

BD bronchodilator, NA not applicable, NS not significant