Comparison 1. Tiotropium versus LABAs.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 HRQoL (SGRQ)	4		Mean Difference (Random, 95% CI)	Totals not selected
2 Subgroup analysis: HRQoL (SGRQ) by type of LABA	4		Mean Difference (Random, 95% CI)	Subtotals only
2.1 Salmeterol	1		Mean Difference (Random, 95% CI)	‐1.4 [‐3.34, 0.54]
2.2 Formoterol	1		Mean Difference (Random, 95% CI)	1.0 [‐1.70, 3.70]
2.3 Indacaterol	2		Mean Difference (Random, 95% CI)	2.1 [0.97, 3.23]
3 Subgroup analysis: HRQoL (SGRQ) by study duration	4		Mean Difference (Random, 95% CI)	Subtotals only
3.1 < 6 months duration	1		Mean Difference (Random, 95% CI)	2.1 [0.56, 3.64]
3.2 ≥ 6 months duration	3		Mean Difference (Random, 95% CI)	0.57 [‐1.69, 2.84]
4 Participants with ≥ 4 units improvement in quality of life (SGRQ)	2		Risk Difference (M‐H, Fixed, 95% CI)	Totals not selected
5 Participants with ≥ 4 units worsening in quality of life (SGRQ)	1		Risk Difference (M‐H, Fixed, 95% CI)	Totals not selected
6 Patients with 1 or more exacerbations	6	12123	Odds Ratio (M‐H, Random, 95% CI)	0.86 [0.79, 0.93]
7 Subgroup analysis: participants with 1 or more exacerbations by type of LABA	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only
7.1 Salmeterol	3	8836	Odds Ratio (M‐H, Random, 95% CI)	0.84 [0.77, 0.92]
7.2 Formoterol	1	431	Odds Ratio (M‐H, Random, 95% CI)	1.32 [0.68, 2.55]
7.3 Indacaterol	2	2856	Odds Ratio (M‐H, Random, 95% CI)	0.92 [0.66, 1.28]
8 Subgroup analysis: participants with 1 or more exacerbations by severity at baseline	1		Odds Ratio (M‐H, Random, 95% CI)	Totals not selected
8.1 GOLD II	1		Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 GOLD III	1		Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8.3 GOLD IV	1		Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9 Subgroup analysis: participants with 1 or more exacerbations by concomitant medication	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected
9.1 ICS users	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
9.2 Non ICS users	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
10 Subgroup analysis: participants with 1 or more exacerbations (hazard ratio) by concomitant medication	1		Hazard Ratio (Fixed, 95% CI)	Totals not selected
10.1 ICS users	1		Hazard Ratio (Fixed, 95% CI)	0.0 [0.0, 0.0]
10.2 Non ICS users	1		Hazard Ratio (Fixed, 95% CI)	0.0 [0.0, 0.0]
11 Subgroup analysis: participants with 1 or more exacerbations by study duration	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only
11.1 < 6 months duration	2	2251	Odds Ratio (M‐H, Random, 95% CI)	0.78 [0.59, 1.04]
11.2 ≥ 6 months duration	4	9872	Odds Ratio (M‐H, Random, 95% CI)	0.90 [0.78, 1.04]
12 Mortality (all‐cause)	6	12123	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.82 [0.60, 1.13]
13 Subgroup analysis: mortality (all cause) by type of LABA	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only
13.1 Salmeterol	3	8836	Odds Ratio (M‐H, Random, 95% CI)	0.69 [0.25, 1.87]
13.2 Formoterol	1	431	Odds Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
13.3 Indacaterol	2	2856	Odds Ratio (M‐H, Random, 95% CI)	4.36 [0.66, 28.70]
14 Subgroup analysis: mortality (all cause) by study duration	6		Odds Ratio (M‐H, Random, 95% CI)	Subtotals only
14.1 < 6 months duration	2	2251	Odds Ratio (M‐H, Random, 95% CI)	3.91 [0.43, 35.45]
14.2 ≥ 6 months duration	4	9872	Odds Ratio (M‐H, Random, 95% CI)	0.77 [0.22, 2.63]
15 Hospitalisations due to COPD exacerbations	4	9267	Odds Ratio (M‐H, Fixed, 95% CI)	0.87 [0.77, 0.99]
16 Hospitalisations (all‐cause)	3	3509	Odds Ratio (M‐H, Random, 95% CI)	0.93 [0.57, 1.54]
17 FEV1 (mL)	5	4600	Mean Difference (IV, Random, 95% CI)	10.52 [‐11.47, 32.51]
18 Symptoms (TDI)	3	3180	Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.63, 0.19]
19 Symptoms (daily total symptom score)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
20 All‐cause, non‐fatal serious adverse events	6	12123	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.78, 0.99]
21 Withdrawals (all‐cause)	6	12123	Odds Ratio (M‐H, Fixed, 95% CI)	0.89 [0.81, 0.99]