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. 2019 Mar 6;2019(3):CD012930. doi: 10.1002/14651858.CD012930.pub2

Comparison 1. LABA/LAMA versus placebo.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1 All‐cause mortality 18 8752 Odds Ratio (M‐H, Fixed, 95% CI) 1.88 [0.81, 4.36]
1.1 IND/GLY 110/50 5 2020 Odds Ratio (M‐H, Fixed, 95% CI) 2.53 [0.61, 10.49]
1.2 UMEC/VI 62.5/25 5 1921 Odds Ratio (M‐H, Fixed, 95% CI) 3.12 [0.68, 14.36]
1.3 UMEC/VI 125/25 4 1401 Odds Ratio (M‐H, Fixed, 95% CI) 0.14 [0.01, 2.83]
1.4 UMEC/VI 500/25 1 51 Odds Ratio (M‐H, Fixed, 95% CI) 0.0 [0.0, 0.0]
1.5 TIO/OLO 2.5/5 6 1670 Odds Ratio (M‐H, Fixed, 95% CI) 2.53 [0.12, 53.43]
1.6 TIO/OLO 5/5 6 1689 Odds Ratio (M‐H, Fixed, 95% CI) 0.0 [0.0, 0.0]
2 SAEs 22 10536 Odds Ratio (M‐H, Fixed, 95% CI) 1.06 [0.88, 1.28]
2.1 IND/GLY 110/50 6 2830 Odds Ratio (M‐H, Fixed, 95% CI) 1.16 [0.86, 1.56]
2.2 UMEC/VI 62.5/25 6 2317 Odds Ratio (M‐H, Fixed, 95% CI) 1.29 [0.86, 1.93]
2.3 UMEC/VI 125/25 4 1403 Odds Ratio (M‐H, Fixed, 95% CI) 0.75 [0.46, 1.22]
2.4 UMEC/VI 500/25 1 51 Odds Ratio (M‐H, Fixed, 95% CI) 0.0 [0.0, 0.0]
2.5 TIO/OLO 2.5/5 6 1670 Odds Ratio (M‐H, Fixed, 95% CI) 0.90 [0.49, 1.68]
2.6 TIO/OLO 5/5 7 1840 Odds Ratio (M‐H, Fixed, 95% CI) 0.97 [0.55, 1.73]
2.7 ACM/FOR 200/6 1 141 Odds Ratio (M‐H, Fixed, 95% CI) 0.51 [0.02, 12.96]
2.8 ACM/FOR 200/12 1 140 Odds Ratio (M‐H, Fixed, 95% CI) 0.51 [0.02, 13.07]
2.9 ACM/FOR 200/18 1 144 Odds Ratio (M‐H, Fixed, 95% CI) 1.11 [0.06, 22.41]
3 AECOPD 3 1127 Odds Ratio (M‐H, Fixed, 95% CI) 0.53 [0.36, 0.78]
3.1 UMEC/VI 62.5/25 2 786 Odds Ratio (M‐H, Fixed, 95% CI) 0.58 [0.37, 0.93]
3.2 UMEC/VI 125/25 1 290 Odds Ratio (M‐H, Fixed, 95% CI) 0.37 [0.17, 0.78]
3.3 UMEC/VI 500/25 1 51 Odds Ratio (M‐H, Fixed, 95% CI) 1.68 [0.08, 35.43]
4 Time to first AECOPD 2 1371 Hazard Ratio (Fixed, 95% CI) 0.44 [0.31, 0.63]
4.1 UMEC/VI 125/25 2 1371 Hazard Ratio (Fixed, 95% CI) 0.44 [0.31, 0.63]
5 Difference vs placebo in adjusted SGRQ score (HRQoL) 8 4952 Mean Difference (Fixed, 95% CI) ‐4.08 [‐4.80, ‐3.36]
5.1 IND/GLY 110/50 2 1370 Mean Difference (Fixed, 95% CI) ‐3.88 [‐5.30, ‐2.45]
5.2 UMEC/VI 62.5/25 3 1425 Mean Difference (Fixed, 95% CI) ‐4.25 [‐5.73, ‐2.77]
5.3 UMEC/VI 125/25 2 1000 Mean Difference (Fixed, 95% CI) ‐3.64 [‐5.48, ‐1.80]
5.4 TIO/OLO 2.5/5 2 579 Mean Difference (Fixed, 95% CI) ‐3.89 [‐5.60, ‐2.17]
5.5 TIO/OLO 5/5 2 578 Mean Difference (Fixed, 95% CI) ‐4.72 [‐6.43, ‐3.01]
6 SGRQ responder analysis 7 4258 Odds Ratio (M‐H, Fixed, 95% CI) 1.75 [1.54, 1.99]
6.1 IND/GLY 110/50 1 706 Odds Ratio (M‐H, Fixed, 95% CI) 1.35 [0.98, 1.86]
6.2 TIO/OLO 2.5/5 2 579 Odds Ratio (M‐H, Fixed, 95% CI) 1.87 [1.30, 2.70]
6.3 TIO/OLO 5/5 2 578 Odds Ratio (M‐H, Fixed, 95% CI) 2.35 [1.63, 3.40]
6.4 UMEC/VI 62.5/25 3 1441 Odds Ratio (M‐H, Fixed, 95% CI) 1.70 [1.37, 2.12]
6.5 UMEC/VI 125/25 2 954 Odds Ratio (M‐H, Fixed, 95% CI) 1.78 [1.35, 2.34]
7 Difference vs placebo in adjusted trough FEV1 at EOT 13 6598 Mean Difference (Fixed, 95% CI) 0.20 [0.19, 0.21]
7.1 IND/GLY 110/50 2 1018 Mean Difference (Fixed, 95% CI) 0.25 [0.22, 0.28]
7.2 UMEC/VI 62.5/25 6 2158 Mean Difference (Fixed, 95% CI) 0.18 [0.17, 0.20]
7.3 UMEC/VI 125/25 4 1304 Mean Difference (Fixed, 95% CI) 0.22 [0.20, 0.25]
7.4 TIO/OLO 2.5/5 3 845 Mean Difference (Fixed, 95% CI) 0.18 [0.15, 0.20]
7.5 TIO/OLO 5/5 3 859 Mean Difference (Fixed, 95% CI) 0.21 [0.18, 0.23]
7.6 ACLID/FORM 200/6 1 137 Mean Difference (Fixed, 95% CI) 0.07 [‐0.04, 0.18]
7.7 ACLID/FORM 200/12 1 137 Mean Difference (Fixed, 95% CI) 0.12 [0.01, 0.22]
7.8 ACLID/FORM 200/18 1 140 Mean Difference (Fixed, 95% CI) 0.08 [‐0.04, 0.19]
8 Difference vs placebo in trough FEV1 at EOT 5 2330 Mean Difference (Fixed, 95% CI) 0.18 [0.16, 0.20]
8.1 IND/GLY 110/50 3 1139 Mean Difference (Fixed, 95% CI) 0.20 [0.17, 0.22]
8.2 TIO/OLO 2.5/5 2 596 Mean Difference (Fixed, 95% CI) 0.16 [0.13, 0.19]
8.3 TIO/OLO 5/5 2 595 Mean Difference (Fixed, 95% CI) 0.16 [0.13, 0.20]
9 Difference vs placebo in trough FEV1 ‐ pooled adjusted and EOT analyses 18   Mean Difference (Fixed, 95% CI) 0.20 [0.19, 0.20]
9.1 IND/GLY 110/50 5   Mean Difference (Fixed, 95% CI) 0.22 [0.21, 0.24]
9.2 UMEC/VI 125/25 4   Mean Difference (Fixed, 95% CI) 0.22 [0.20, 0.25]
9.3 UMEC/VI 62.5/25 6   Mean Difference (Fixed, 95% CI) 0.18 [0.17, 0.20]
9.4 TIO/OLO 2.5/5 5   Mean Difference (Fixed, 95% CI) 0.17 [0.15, 0.19]
9.5 TIO/OLO 5/5 5   Mean Difference (Fixed, 95% CI) 0.19 [0.17, 0.21]
9.6 ACLID/FORM 200/6 1   Mean Difference (Fixed, 95% CI) 0.07 [‐0.04, 0.18]
9.7 ACLID/FORM 200/12 1   Mean Difference (Fixed, 95% CI) 0.12 [0.01, 0.22]
9.8 ACLID/FORM 200/18 1   Mean Difference (Fixed, 95% CI) 0.08 [‐0.04, 0.19]
10 Difference vs placebo in adjusted peak FEV1 7 4188 Mean Difference (Fixed, 95% CI) 0.31 [0.29, 0.32]
10.1 IND/GLY 110/50 2 1094 Mean Difference (Fixed, 95% CI) 0.35 [0.32, 0.38]
10.2 UMEC/VI 62.5/25 1 693 Mean Difference (Fixed, 95% CI) 0.22 [0.18, 0.27]
10.3 UMEC/VI 125/25 1 678 Mean Difference (Fixed, 95% CI) 0.28 [0.24, 0.32]
10.4 TIO/OLO 2.5/5 2 644 Mean Difference (Fixed, 95% CI) 0.29 [0.27, 0.32]
10.5 TIO/OLO 5/5 2 656 Mean Difference (Fixed, 95% CI) 0.33 [0.30, 0.35]
10.6 ACLID/FORM 200/6 1 140 Mean Difference (Fixed, 95% CI) 0.25 [0.13, 0.37]
10.7 ACLID/FORM 200/12 1 139 Mean Difference (Fixed, 95% CI) 0.31 [0.20, 0.43]
10.8 ACLID/FORM 200/18 1 144 Mean Difference (Fixed, 95% CI) 0.31 [0.19, 0.42]
11 AEs 17 8235 Odds Ratio (M‐H, Fixed, 95% CI) 0.95 [0.86, 1.04]
11.1 IND/GLY 110/50 6 2830 Odds Ratio (M‐H, Fixed, 95% CI) 0.90 [0.76, 1.07]
11.2 UMEC/VI 62.5/25 5 1921 Odds Ratio (M‐H, Fixed, 95% CI) 1.07 [0.88, 1.29]
11.3 UMEC/VI 125/25 4 1401 Odds Ratio (M‐H, Fixed, 95% CI) 1.08 [0.86, 1.34]
11.4 UMEC/VI 500/25 1 51 Odds Ratio (M‐H, Fixed, 95% CI) 2.84 [0.32, 25.36]
11.5 TIO/OLO 2.5/5 4 1011 Odds Ratio (M‐H, Fixed, 95% CI) 0.85 [0.66, 1.11]
11.6 TIO/OLO 5/5 4 1021 Odds Ratio (M‐H, Fixed, 95% CI) 0.78 [0.60, 1.01]