Table 2. Primary outcome and prespecified subgroups analysis.
| Outcomes | All studies | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| n | References |
Random effect model | Fixed effects model | Homogeneity | |||||
| SMD | 95% CI (p value) | SMD | 95% CI (p value) | P value | I2 (%) | ||||
| Primary outcome | |||||||||
| Exercise capacity | 15 |
[11, 12, 16, 23, 25–27, 30–37] | 0.29 | 0.08–0.50 (p = 0.006) | 0.21 | 0.11–0.30 (p<0.001) | <0.001 | 72 | |
| Type of exercise test | |||||||||
| 6MWT | 9 | [12, 16, 26, 27, 31, 32, 35–37] | MD: 14.1 | -5.6–33.7 (p = 0.16) | MD: 18.4 | 7.8–29.1 (p<0.001) | 0.03 | 53 | |
| VO2 max | 5 | [11, 23, 25, 33, 34] | MD: 2.62 | 1.08–4.16 (p<0.001) | MD: 2.82 |
2.1–3.6 (p<0.001) | 0.03 | 64 | |
| Treadmill | 1 | [30] | MD: -1.0 | -52.7–50.7 (p = 0.97) | MD: -1.0 | -52.7–50.7 (p = 0.97) | N/A | N/A | |
| Classes of PH-targeted therapies | |||||||||
| PDE-5i | 8 | [11, 12, 23, 25, 26, 32–34] | 0.54 | 0.12–0.96 (p = 0.01) | 0.33 | 0.16–0.51 (p<0.001) | <0.001 | 80 | |
| ERA | 4 | [16, 27, 30, 31] | -0.02 |
-0.18–0.14 (p = 0.81) | -0.02 |
-0.18–0.14 (p = 0.81) | 0.91 | 0 | |
| sGC stimulators | 1 | [37] | 0.02 | -0.30–0.35 (p = 0.90) | 0.02 | -0.30–0.35 (p = 0.90) | N/A | N/A | |
| Prostanoids | 2 | [35, 36] | 0.39 | 0.22–0.57 (p<0.001) | 0.39 | 0.22–0.57 (p<0.001) | 0.58 | 0 | |
| Pulmonary hypertension | |||||||||
| With PH | 7 | [12, 16, 23, 31, 34, 35, 37] | 0.25 | 0.07–0.42 (p = 0.006) | 0.28 | 0.14–0.41 (p<0.001) | 0.30 | 17 | |
| Without PH/Unknown | 8 | [11, 25–27, 30, 32, 33, 36] | 0.40 | 0.05–0.75 (p = 0.03) | 0.15 | 0.02–0.27 (p = 0.03) | <0.001 | 83 | |
| Left ventricular ejection fraction | |||||||||
| Preserved | 4 | [30–32, 34] | 0.13 | -0.07–0.33 (p = 0.20) | 0.13 | -0.07–0.33 (p = 0.20) | 0.51 | 0 | |
| Reduced | 10 | [11, 12, 23, 25–27, 33, 35–37] | 0.43 | 0.13–0.72 (p = 0.005) |
0.24 | 0.23–0.35 (p<0.001) | <0.001 | 81 | |
| Both | 1 | [16] | 0.04 | -0.46–0.53 (p = 0.89) |
0.04 | -0.46–0.53 (p = 0.89) | N/A | N/A | |
| Study duration | |||||||||
| ≤ 6 months | 8 | [12, 16, 26, 31, 33, 34, 36, 37] | 0.17 | -0.10–0.44 (p = 0.21) |
0.11 | -0.07–0.29 (p = 0.24) | 0.05 | 49 | |
| > 6 months | 7 | [11, 23, 25, 27, 30, 32, 35] | 0.40 | 0.09–0.72 (p = 0.01) |
0.24 | 0.13–0.35 (p<0.001) | <0.001 | 83 | |
| NYHA functional class | |||||||||
| Up to II | 0 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| Up to III | 8 | [11, 16, 25, 26, 30, 31, 33, 34] | 0.36 | -0.09–0.81 (p = 0.11) |
0.18 | 0.00–0.36 (p = 0.05) | <0.001 | 82 | |
| Up to IV | 7 | [12, 23, 27, 32, 35–37] | 0.24 | 0.05–0.42 (p = 0.01) |
0.22 | 0.11–0.33 (p<0.001) | 0.05 | 51 | |