Statistically significant network meta-analysis results
| Treatment comparison | NMA estimate OR (95% CI) | CI | MA estimate OR (95% CI) | CI | Number of studies (Number of patients) | MA Heterogeneity variance |
|---|---|---|---|---|---|---|
| Exacerbation past year—20 studies, 17 treatments, 26 141 patients | ||||||
| FLUT/SALM vs SALM | 0.85 | 0.75–0.97 | 0.82 | 0.70–0.95 | 4 (2784) | 0.00 |
| TIOT vs INDAC | 0.83 | 0.72 to 0.96 | 0.83 | 0.72 to 0.96 | 1 (3439) | – |
| TIOT vs SALM | 0.82 | 0.73 to 0.93 | 0.84 | 0.76 to 0.92 | 1 (7376) | – |
| SALM vs placebo | 0.79 | 0.64 to 0.97 | 0.80 | 0.58 to 1.09 | 1 (634) | – |
| INDAC vs placebo | 0.78 | 0.61 to 1.00 | ||||
| BUDE/FORM vs FORM | 0.76 | 0.64 to 0.91 | 0.76 | 0.62 to 0.93 | 4 (3080) | 0.01 |
| FLUT/F vs VILA | 0.75 | 0.62 to 0.92 | 0.75 | 0.61 to 0.94 | 2 (1624) | 0.00 |
| INDAC/GLYC vs TIOT | 0.74 | 0.60 to 0.91 | 0.74 | 0.60 to 0.91 | 1 (1466) | – |
| INDAC/GLYC vs FLUT/SALM | 0.71 | 0.55 to 0.92 | ||||
| FLUT/SALM vs Placebo | 0.67 | 0.53 to 0.85 | ||||
| TIOT vs Placebo | 0.65 | 0.53 to 0.79 | 0.64 | 0.50 to 0.83 | 1 (1003) | – |
| BUDE/FORM vs placebo | 0.64 | 0.45 to 0.91 | 0.55 | 0.36 to 0.83 | 1 (519) | – |
| INDAC/GLYC vs GLYC | 0.63 | 0.51 to 0.78 | 0.63 | 0.51 to 0.77 | 1 (1469) | – |
| INDAC/GLYC vs INDAC | 0.62 | 0.48 to 0.79 | ||||
| INDAC/GLYC vs SALM | 0.61 | 0.48 to 0.78 | ||||
| TIOT/FLUT/SALM vs placebo | 0.58 | 0.35 to 0.96 | ||||
| INDAC/GLYC vs FORM | 0.57 | 0.36 to 0.90 | ||||
| TIOT/BUDE/FORM vs INDAC/GLYC | 0.48 | 0.28 to 0.83 | ||||
| INDAC/GLYC vs placebo | 0.48 | 0.36 to 0.64 | ||||
| TIOT/BUDE/FORM vs TIOT/FLUT/SALM | 0.40 | 0.21 to 0.80 | ||||
| TIOT/BUDE/FORM vs BUDE/FORM | 0.36 | 0.19 to 0.69 | ||||
| TIOT/BUDE/FORM vs TIOT | 0.36 | 0.22 to 0.59 | 0.36 | 0.22 to 0.59 | 1 (660) | – |
| TIOT/BUDE/FORM vs FLUT/SALM | 0.35 | 0.21 to 0.58 | ||||
| TIOT/BUDE/FORM vs TIOT/SALM | 0.33 | 0.17 to 0.65 | ||||
| TIOT/BUDE/FORM vs BECL/FORM | 0.32 | 0.15 to 0.65 | ||||
| TIOT/BUDE/FORM vs BUDE | 0.31 | 0.16 to 0.60 | ||||
| TIOT/BUDE/FORM vs GLYC | 0.30 | 0.18 to 0.52 | ||||
| TIOT/BUDE/FORM vs INDAC | 0.30 | 0.18 to 0.50 | ||||
| TIOT/BUDE/FORM vs SALM | 0.30 | 0.18 to 0.49 | ||||
| TIOT/BUDE/FORM vs FLUT | 0.29 | 0.14 to 0.60 | ||||
| TIOT/BUDE/FORM vs FORM | 0.28 | 0.15 to 0.52 | ||||
| TIOT/BUDE/FORM vs placebo | 0.23 | 0.14 to 0.40 | ||||
| Between-study heterogeneity variance for NMA | 0.00 | |||||
| Design-by-treatment interaction model for inconsistency χ² (df, p value, heterogeneity) | 3.37 (4, 0.498, 0.00) | |||||
| Mortality overall—88 studies, 28 treatments, 97 526 patients | ||||||
| FORM vs FLUT/SALM | 1.64 | 1.01 to 2.67 | 0.00 | |||
| FLUT/SALM vs Placebo | 0.78 | 0.63 to 0.96 | 0.81 | 0.66 to 1.00 | 6 (4852) | 0.00 |
| FLUT/SALM vs FLUT | 0.75 | 0.60 to 0.94 | 0.76 | 0.62 to 0.93 | 3 (3752) | 0.00 |
| Between-study heterogeneity variance for NMA | 0.00 | |||||
| Design-by-treatment interaction model for inconsistency χ² (df, p value, heterogeneity) | 31.44 (50, 0.982, 0.00) | |||||
| Cardiovascular-related mortality—37 studies, 20 treatments, 55 156 patients | ||||||
| TIOT+Resp vs SALM | 2.32 | 1.38 to 3.88 | ||||
| TIOT vs SALM | 2.00 | 1.23 to 3.26 | 1.32 | 0.46 to 3.81 | 1 (7798) | – |
| TIOT+Resp vs FLUT/SALM | 1.87 | 1.14 to 3.06 | ||||
| TIOT+Resp vs FLUT | 1.75 | 1.04 to 2.94 | ||||
| TIOT vs FLUT/SALM | 1.61 | 1.02 to 2.56 | 2.12 | 0.95 to 4.72 | 1 (1448) | – |
| SALM vs placebo | 0.63 | 0.45 to 0.88 | 0.60 | 0.42 to 0.87 | 4 (5171) | 0.00 |
| Between-study heterogeneity variance for NMA | 0.00 | |||||
| Design-by-treatment interaction model for inconsistency χ² (df, p value, heterogeneity) | 11.79 (27, 0.995, 0.00) | |||||
| Pneumonia—54 studies, 21 treatments, 61 551 patients | ||||||
| FLUT/VILA vs ACLI | 3.15 | 1.07 to 9.24 | ||||
| FLUT/VILA vs BUDE | 2.83 | 1.10 to 7.25 | ||||
| FLUT/SALM vs ACLI | 2.81 | 1.30 to 6.07 | ||||
| FLUT/VILA vs GLYC | 2.59 | 1.09 to 6.18 | ||||
| FLUT/SALM vs BUDE | 2.52 | 1.44 to 4.43 | ||||
| FLUT/SALM vs GLYC | 2.31 | 1.47 to 3.64 | ||||
| FLUT/VILA vs TIOT | 2.25 | 1.02 to 4.96 | ||||
| FLUT vs BUDE | 2.21 | 1.25 to 3.92 | ||||
| FLUT/SALM vs FORM | 2.09 | 1.29 to 3.37 | ||||
| FLUT/SALM vs TIOT | 2.00 | 1.52 to 2.64 | 2.20 | 1.33 to 3.62 | 1 (1323) | – |
| FLUT/SALM vs INDAC | 1.95 | 1.20 to 3.17 | ||||
| FLUT/SALM vs placebo | 1.90 | 1.53 to 2.34 | 1.75 | 1.44 to 2.13 | 4 (3872) | <0.0001 |
| FLUT/VILA vs VILA | 1.87 | 1.18 to 2.96 | 1.90 | 1.20 to 3.01 | 4 (2442) | 0.00 |
| FLUT/SALM vs SALM | 1.70 | 1.38 to 2.09 | 1.69 | 1.40 to 2.04 | 8 (7613) | 0.00 |
| FLUT vs placebo | 1.66 | 1.32 to 2.08 | 1.60 | 1.32 to 1.95 | 5 (4258) | 0.00 |
| SALM vs FLUT | 0.67 | 0.54 to 0.84 | 0.68 | 0.56 to 0.83 | 2 (3174) | 0.00 |
| INDAC vs FLUT | 0.58 | 0.36 to 0.95 | ||||
| TIOT vs FLUT | 0.57 | 0.43 to 0.75 | ||||
| FORM vs FLUT | 0.55 | 0.33 to 0.90 | ||||
| INDAC/GLYC vs FLUT | 0.51 | 0.31 to 0.85 | ||||
| GLYC vs FLUT | 0.49 | 0.31 to 0.78 | ||||
| INDAC/GLYC vs FLUT/SALM | 0.45 | 0.27 to 0.75 | 0.11 | 0.01 to 2.09 | 1 (522) | – |
| ACLI vs FLUT | 0.41 | 0.19 to 0.88 | ||||
| INDAC/GLYC vs FLUT/VILA | 0.40 | 0.16 to 0.98 | ||||
| Between-study heterogeneity variance for NMA | 0.01 | |||||
| Design-by-treatment interaction model for inconsistency χ² (d.f., p value, heterogeneity) | 34.33 (31, 0.311, 0.00) | |||||
ACLI, aclidinium bromide; BECL, beclomethasone; BUDE, budesonide; d.f., degrees of freedom; FLUT, fluticasone; FORM, formoterol; GLYC, glycopyrronium bromide; INDAC, indacaterol; MA, meta-analysis; NMA, network meta-analysis; SALM, salmeterol; TIOT, tiotropium; TIOT+Resp, Tiotropium Respimat (Soft Mist Inhaler); VILA, vilanterol.