Comparison 2. Group 1 Pulmonary Arterial Hypertension ‐ PDE5i versus placebo, on combination therapy.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Improvement in WHO functional Class	2	227	Odds Ratio (M‐H, Fixed, 95% CI)	1.20 [0.66, 2.17]
2 Six‐minute walk distance	4	509	Mean Difference (Fixed, 95% CI)	19.66 [9.22, 30.10]
3 Mortality	3	492	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.07, 1.06]
4 PAP	2	387	Mean Difference (Fixed, 95% CI)	‐4.58 [‐6.14, ‐3.01]
5 Cardiac Output	3	310	Mean Difference (Fixed, 95% CI)	0.87 [0.53, 1.21]
6 PVR	3	303	Std. Mean Difference (Fixed, 95% CI)	‐0.48 [‐0.72, ‐0.25]
7 Clinical worsening	4	717	Odds Ratio (M‐H, Fixed, 95% CI)	0.38 [0.21, 0.68]
8 Adverse events	5		Odds Ratio (M‐H, Fixed, 95% CI)	Subtotals only
8.1 Headache	5	768	Odds Ratio (M‐H, Fixed, 95% CI)	2.49 [1.74, 3.56]
8.2 GI upset	4	726	Odds Ratio (M‐H, Fixed, 95% CI)	1.95 [1.30, 2.93]
8.3 Flushing	2	368	Odds Ratio (M‐H, Fixed, 95% CI)	1.11 [0.63, 1.96]
8.4 Muscle and joint pain	3	494	Odds Ratio (M‐H, Fixed, 95% CI)	2.17 [1.28, 3.67]
8.5 Epistaxis	2	358	Odds Ratio (M‐H, Fixed, 95% CI)	1.32 [0.34, 5.12]
8.6 Visual disturbance	2	368	Odds Ratio (M‐H, Fixed, 95% CI)	3.95 [0.97, 16.08]