Table 2 Characteristics of controlled trials comparing pulmonary arterial hypertension (PAH) oral treatments and placebo for exercise capacity in the whole population and connective tissue disease (CTD) subset of patients

Author (year)	Quality (Jadad)	Patients with SSc	Inclusion criteria for PAH	Intervention	Comparator	Study duration	Outcome	Effect size (95% CI)
Channick et al (2001)19	5/5	n = 5 (16%)	Idiopathic and CTDWHO III/IV6MWT 150–500 mmPAP>25 mmHg, PVR>240	Bosentan 62.5 mg×2/day for 4 weeks, then 125 mg×2/day for 8 weeks	Placebo	12 weeks	6MWT	0.87 (0.08 to 1.67)
Rubin et al (2002)9	5/5	n = 47 (22%)	Idiopathic and CTDWHO III/IV6MWT 150–450 mmPAP>25 mmHg, PVR>240	Bosentan 62.5 mg×2/day for 4 weeks, then:	Placebo	16 weeks	6MWT
				125 mg×2/day			125 mg×2/day	0.47 (0.13 to 0.80)
				250 mg/day			250 mg/day	0.71 (0.36 to 1.06)
Denton et al (2006)21	5/5	n = 52 (79%)	CTD-related PAHWHO III/IV6MWT 150–500 mmPAP>25 mmHg, PVR>240	Bosentan 62.5 mg×2/day for 4 weeks then 125 mg×2/day or 250 mg/day	Placebo	12 to 16 weeks	6MWT	0.30 (−0.2 to 0.8)
Barst et al (2004)23	4/5	n = 26 (15%)	Idiopathic and CTDWHO II, III and IVNo limit for the 6MWTmPAP>25 mmHg at rest	Sitaxsentan	Placebo	12 weeks	6MWT
				100 mg/day			100 mg/day	0.29 (−0.05 to 0.67)
				300 mg/day			300 mg/day	0.31 (−0.06 to 0.65)
Langleben et al (2004)25	4/5	No data	Idiopathic and CTDWHOIII and IV6MWT>450 m excludedPVR⩾240	Sitaxsentan100 mg/day or 300 mg/day	Placebo	12 weeks	6MWT	0.70 (0.18 to 1.22)
Barst et al (2006)22	4/5	No data	Idiopathic and CTDWHO II, III and IVmPAP>25 mmHg at restPVR⩾240	Sitaxsentan	Placebo	18 weeks	6MWT
				50 mg/day			50 mg/day	0.29 (−0.06 to 0.65)
				100 mg/day			100 mg/day	0.40 (0.04 to 0.76)
Seibold et al (2006)24	4/5	n = 63 (57%)	CTD-related PAHWHO II, III and IV6MWT>450 m excludedmPAP>25 mmHg at rest PVR⩾240	Sitaxsentan	Placebo	12 to 18 weeks	6MWT
Girgis et al (2007)29				50 mg/day			50 mg/day	0.16 (−0.39 to 0.71)
				100 mg/day			100 mg/day	0.39 (−0.20 to 0.78)
				300 mg/day			300 mg/day	0.17 (−0.36 to 0.85)
Galie et al (2005)12	5/5	n = 38 (14%)	Idiopathic and CTDWHO II-IV6MWT 100–450 mmPAP⩾25 mmHg	Sildenafil	Placebo	12 weeks	6MWT
				20 mg×3/day			20 mg×3/day	0.53 (0.18 to 0.87)
				40 mg×3/day			40 mg×3/day	0.58 (0.23 to 0.92)
				80 mg×3/day			80 mg×3/day	0.63 (0.29 to 0.97)
Simmonneau et al (2006)26	5/5	n = 38 (45%)	CTD-related PAHWHO II–IV6MWT 100–450 mmPAP⩾25 mmHg	Sildenafil	Placebo	12 weeks	6MWT
				20 mg×3/day			20 mg×3/day	0.64 (−0.01 to 1.25)
				40 mg×3/day			40 mg×3/day	0.62 (−0.03 to 1.24)
				80 mg×3/day			80 mg×3/day	0.35 (−0.29 to 0.98)

6MWT, 6-min walk test; CI, confidence interval; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; SSc, systemic sclerosis; WHO, World Health Organization.