Comparison 1. Group 1 Pulmonary Arterial Hypertension ‐ PDE5i versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Improvement in WHO functional class	4	282	Odds Ratio (M‐H, Fixed, 95% CI)	8.59 [3.95, 18.72]
1.1 Sildenafil	1	146	Odds Ratio (M‐H, Fixed, 95% CI)	10.24 [3.69, 28.47]
1.2 Tadalafil	2	72	Odds Ratio (M‐H, Fixed, 95% CI)	7.71 [1.88, 31.72]
1.3 Vardenafil	1	64	Odds Ratio (M‐H, Fixed, 95% CI)	5.59 [0.66, 47.07]
2 Six‐minute walk distance	8	880	Mean Difference (Fixed, 95% CI)	48.17 [40.30, 56.04]
2.1 Sildenafil	4	339	Mean Difference (Fixed, 95% CI)	56.91 [44.40, 69.41]
2.2 Tadalafil	3	477	Mean Difference (Fixed, 95% CI)	38.46 [27.60, 49.31]
2.3 Vardenafil	1	64	Mean Difference (Fixed, 95% CI)	69.0 [41.00, 97.00]
3 Mortality	8	1119	Odds Ratio (M‐H, Fixed, 95% CI)	0.22 [0.07, 0.68]
3.1 Sildenafil	5	634	Odds Ratio (M‐H, Fixed, 95% CI)	0.23 [0.05, 0.98]
3.2 Tadalafil	2	421	Odds Ratio (M‐H, Fixed, 95% CI)	0.50 [0.05, 5.63]
3.3 Vardenafil	1	64	Odds Ratio (M‐H, Fixed, 95% CI)	0.08 [0.00, 1.82]
4 PAP	6	453	Mean Difference (Fixed, 95% CI)	‐6.43 [‐8.13, ‐4.74]
4.1 Sildenafil	4	333	Mean Difference (Fixed, 95% CI)	‐7.34 [‐9.35, ‐5.33]
4.2 Tadalafil	1	56	Mean Difference (Fixed, 95% CI)	‐3.67 [‐7.55, 0.21]
4.3 Vardenafil	1	64	Mean Difference (Fixed, 95% CI)	‐5.3 [‐10.60, ‐0.00]
5 RAP	3	341	Mean Difference (Fixed, 95% CI)	‐1.35 [‐2.34, ‐0.36]
5.1 Sildenafil	2	277	Mean Difference (Fixed, 95% CI)	‐1.20 [‐2.30, ‐0.11]
5.2 Vardenafil	1	64	Mean Difference (Fixed, 95% CI)	‐2.0 [‐4.30, 0.30]
6 CI	4	239	Mean Difference (Fixed, 95% CI)	0.28 [0.16, 0.40]
6.1 Sildenafil	2	152	Mean Difference (Fixed, 95% CI)	0.47 [0.28, 0.66]
6.2 Tadalafil	1	28	Mean Difference (Fixed, 95% CI)	0.02 [‐0.18, 0.22]
6.3 Vardenafil	1	59	Mean Difference (Fixed, 95% CI)	0.4 [0.10, 0.70]
7 PVR	3	266	Mean Difference (Fixed, 95% CI)	‐4.74 [‐6.13, ‐3.35]
7.1 Sildenafil	1	146	Mean Difference (Fixed, 95% CI)	‐3.87 [‐5.67, ‐2.08]
7.2 Tadalafil	1	56	Mean Difference (Fixed, 95% CI)	‐7.32 [‐10.42, ‐4.22]
7.3 Vardenafil	1	64	Mean Difference (Fixed, 95% CI)	‐4.7 [‐7.80, ‐1.60]
8 PASP	2	48	Mean Difference (Fixed, 95% CI)	‐11.62 [‐25.18, 1.94]
8.1 Sildenafil	1	24	Mean Difference (Fixed, 95% CI)	‐7.0 [‐23.64, 9.64]
8.2 Tadalafil	1	24	Mean Difference (Fixed, 95% CI)	‐20.75 [‐44.14, 2.64]
9 Dyspnoea	4	239	Mean Difference (Fixed, 95% CI)	‐0.72 [‐0.99, ‐0.44]
9.1 Sildenafil	2	155	Mean Difference (Fixed, 95% CI)	‐0.57 [‐0.90, ‐0.24]
9.2 Tadalafil	1	20	Mean Difference (Fixed, 95% CI)	‐0.64 [‐1.65, 0.37]
9.3 Vardenafil	1	64	Mean Difference (Fixed, 95% CI)	‐1.15 [‐1.70, ‐0.60]
10 Clinical worsening requiring intervention	3	746	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.27, 1.23]
10.1 Sildenafil	1	277	Odds Ratio (M‐H, Fixed, 95% CI)	0.46 [0.17, 1.25]
10.2 Tadalafil	1	405	Odds Ratio (M‐H, Fixed, 95% CI)	1.28 [0.27, 5.95]
10.3 Vardenafil	1	64	Odds Ratio (M‐H, Fixed, 95% CI)	0.21 [0.02, 2.46]
11 Adverse events	5		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
11.1 Headache	5	848	Odds Ratio (M‐H, Fixed, 95% CI)	1.97 [1.33, 2.92]
11.2 GI upset	5	848	Odds Ratio (M‐H, Fixed, 95% CI)	1.63 [1.07, 2.48]
11.3 Flushing	3	748	Odds Ratio (M‐H, Fixed, 95% CI)	4.12 [1.83, 9.26]
11.4 Muscle and joint pain	4	792	Odds Ratio (M‐H, Fixed, 95% CI)	2.52 [1.59, 3.99]
11.5 Epistaxis	2	682	Odds Ratio (M‐H, Fixed, 95% CI)	2.37 [0.83, 6.77]
11.6 Respiratory symptoms	3	748	Odds Ratio (M‐H, Fixed, 95% CI)	1.74 [0.89, 3.40]
11.7 Visual disturbance	3	748	Odds Ratio (M‐H, Fixed, 95% CI)	2.04 [0.58, 7.14]