2. Sensitivity analysis: fixed‐effect versus random‐effects.
| Meta‐analysis | Number of studies | Effect measure | Fixed‐effect size and CI | Random‐effect size and CI |
| Group 1 Pulmonary arterial hypertension ‐ PDE5i versus placebo | ||||
| Improvement in WHO functional class | 4 | OR | 8.59 (3.95 to 18.72) | 8.53 (3.90 to 18.67) |
| Six‐minute walk distance | 8 | MD | 48.17 (40.30 to 56.04) | 52.98 (40.74 to 65.23)1 |
| Mortality | 7 | OR | 0.22 (0.07 to 0.68) | 0.28 (0.08 to 0.95) |
| PAP | 5 | MD | −6.33 (−8.12 to −4.53) | −8.94 (−13.73 to −4.15) |
| RAP | 2 | MD | −1.52 (−2.79 to −0.24) | −1.52 (−2.79 to −0.24) |
| Cardiac index | 4 | MD | 0.28 (0.16 to 0.40) | 0.35 (0.08 to 0.61)a |
| PVR | 3 | MD | −4.74 (−6.13 to −3.35) | −5.02 (−7.02 to −3.02) |
| PASP | 2 | MD | −11.62 (−25.18 to 1.94) | −11.62 (−25.18 to 1.94) |
| Dypnoea | 4 | MD | −0.72 (−0.99 to −0.44) | −0.61 (−1.19 to −0.02) |
| Clinical worsening requiring intervention | 3 | OR | 0.58 (0.27 to 1.23) | 0.55 (0.25 to 1.23) |
| Group 1 Pulmonary arterial hypertension ‐ PDE5i versus placebo to on combination therapy | ||||
| Improvement in WHO functional Class | 2 | OR | 1.20 (0.66 to 2.17) | 1.09 (0.41 to 2.92) |
| Six‐minute walk distance | 4 | MD | 19.66 (9.22 to 30.10) | 18.94 (0.23 to 37.65) |
| Mortality | 3 | OR | 0.26 (0.07 to 1.06) | 0.38 (0.04 to 3.81) |
| PAP | 2 | MD | −4.58 (−6.14 to −3.01) | −5.12 (−8.21 to −2.03) |
| Cardiac output | 2 | MD | 0.87 (0.53 to 1.21) | 0.87 (0.53 to 1.21) |
| PVR | 3 | SMD | −0.48 (−0.72 to −0.25) | −0.36 (−0.84 to 0.12)a |
| Clinical worsening | 3 | OR | 0.34 (0.18 to 0.63) | 0.34 (0.18 to 0.63) |
| Group 1 Pulmonary arterial hypertension ‐ PDE5i versus ERA | ||||
| Improvement in WHO functional Class | 1 | OR | 0.94 (0.55 to 1.60) | 0.94 (0.55 to 1.60) |
| Six‐minute walk distance | 2 | MD | 49.38 (3.65 to 95.11) | 49.38 (3.65 to 95.11) |
| Mortality | 2 | OR | 3.19 (0.74 to 13.64) | 3.19 (0.74 to 13.64) |
| Quality of life | 1 | MD | 22.00 (9.00 to 35.00) | 22.00 (9.00 to 35.00) |
| PAP | 1 | MD | 7.00 (−4.82 to 18.82) | 7.00 (−4.82 to 18.82) |
| RAP | 1 | MD | 2.00 (−2.14 to 6.14) | 2.00 (−2.14 to 6.14) |
| Cardiac index | 1 | MD | 0.00 (−0.49 to 0.49) | 0.00 (−0.49 to 0.49) |
| PVR | 1 | MD | 0.00 (−1.93 to 1.93) | 0.00 (−1.93 to 1.93) |
| Clinical worsening | 2 | OR | 0.52 (0.30 to 0.89) | 0.52 (0.30 to 0.89) |
| Group 2 Pulmonary hypertension due to left‐heart disease | ||||
| Improvement in WHO functional Class | 3 | OR | 0.53 (0.32 to 0.87) | 0.70 (0.20 to 2.37) |
| Six‐minute walk distance | 3 | MD | 34.31 (22.75 to 45.87) | 28.44 (‐1.82 to 58.69)a |
| Mortality | 3 | OR | 0.01 (−0.03 to 0.04) | 0.01 (−0.03 to 0.04) |
| Mean PAP | 3 | MD | −10.17 (−11.99 to −8.35) | −6.58 (−22.28 to 9.12)a |
| Cardiac index | 2 | MD | 0.07 (−0.17 to 0.30) | 0.06 (−0.22 to 0.34) |
| TPG | 1 | MD | −14.60 (−15.63 to −13.57) | −14.60 (−15.63 to −13.57) |
| RAP | 1 | MD | −1.00 (−3.77 to 1.77) | −1.00 (−3.77 to 1.77) |
| PASP | 1 | MD | −27.60 (−30.37 to −24.83) | −27.60 (−30.37 to −24.83) |
| Dypnoea | 1 | MD | 1.15 (0.51 to 1.79) | 1.15 (0.51 to 1.79) |
| Clinical worsening requiring intervention | 2 | OR | 1.19 (0.66 to 2.14) | 0.87 (0.22 to 3.46) |
| Group 3 Pulmonary hypertension due to lung disease | ||||
| Improvement in WHO functional Class | 1 | OR | 44.33 (4.78 to 410.93) | 44.33 (4.78 to 410.93) |
| Six‐minute walk distance | 5 | MD | 14.04 (7.05 to 21.02) | 26.70 (2.00 to 51.39)1 |
| Mean PAP | 2 | MD | −0.14 (−6.65 to 6.37) | −0.14 (−6.65 to 6.37) |
| Cardiac index | 1 | MD | 0.30 (−0.14 to 0.74) | 0.30 (−0.14 to 0.74) |
| PVR | 1 | MD | −1.31 (−3.67 to 1.05) | −1.31 (−3.67 to 1.05) |
| RAP | 1 | MD | 0.36 (−2.76 to 3.48) | 0.36 (−2.76 to 3.48) |
| Quality of life | 3 | MD | 0.19 (−0.07 to 0.44) | 0.19 (−0.07 to 0.44) |
| Group 4 Pulmonary hypertension due to CTEPH | ||||
| Improvement in WHO functional Class | 1 | OR | 17.18 (0.78 to 380.85) | 17.18 (0.78 to 380.85) |
| Six‐minute walk distance | 3 | MD | 18.73 (−12.72 to 50.19) | 18.73 (−12.72 to 50.19) |
| Mortality | 2 | OR | 0.01 (−0.06 to 0.08) | 0.01 (−0.06 to 0.08) |
| Mean PAP | 2 | MD | −1.79 (−5.55 to 1.96) | −1.67 (−6.48 to 3.15) |
| Cardiac index | 3 | MD | 0.03 (−0.19 to 0.25) | 0.03 (−0.19 to 0.25) |
| PVR | 3 | MD | −0.07 (−0.32 to 0.18) | −0.12 (−0.50 to 0.25) |
| RAP | 2 | MD | −0.98 (−3.42 to 1.47) | −0.98 (−3.42 to 1.47) |
| Quality of life | 1 | MD | −0.26 (−1.17 to 0.64) | −0.26 (−1.17 to 0.64) |
| Mixed pulmonary hypertension group 2 to 4 | ||||
| Improvement in WHO functional Class | 2 | OR | 11.33 (4.91 to 26.15) | 11.33 (4.91 to 26.15) |
| Six‐minute walk distance | 1 | MD | 50.97 (44.88 to 57.06) | 50.97 (44.88 to 57.06) |
| PASP | 2 | MD | −10.00 (−11.92 to −8.08) | −10.00 (−11.92 to −8.08) |
astatistically high heterogeneity
CI ‐ confidence interval; CTEPH ‐ chronic thromboembolic pulmonary hypertension; OR ‐ odds ratio; MD ‐ mean difference; PAP ‐ pulmonary artery pressure; PASP ‐ pulmonary artery systemic pressure; PDE5i ‐ phosphodiesterase‐5 inhibitor; PVR ‐ pulmonary vascular resistance; RAP ‐ right atrial pressure; SMD ‐ standardised mean difference; TPG ‐ transpulmonary gradient; WHO ‐ World Health Organization