Table 1. Summarized characteristics of included randomized controlled trials.

Source	Groups	Baseline therapy	N	Mean Age (y)	Female (%)	WHO FC [%]	Duration (weeks)	Etiology [%]	Outcome Measures
Channick et al., 2001 (17)	Bosentan 125 mg bid	Conventional therapy	21	52.2	81.0	III [100]	12	IPAH [84], APAH [16]	LIVER
	Placebo		11	47.4	100.0
Rubin et al., 2002 (BREATHE-1) (18)	Bosentan 125 mg bid	Conventional therapy	74	50.4	77.0	III [92]	16	IPAH [70], APAH [30]	LIVER
	Placebo		69	47.2	78.3	IV [8]
Humbert et al., 2004 (BREATHE-2) (19)	Bosentan 125 mg bid	Epoprostenol	22	45.0	77.3	III [76]	16	IPAH [82], APAH [18]	LIVER, Edema, Anemia
	Placebo		11	47.0	54.5	IV [24]
Galiè et al., 2006 (BREATHE-5) (20)	Bosentan 125 mg bid	Conventional therapy	37	37.2	62.2	NA	16	APAH [100]	LIVER, Edema
	Placebo		17	44.2	58.8
Galiè et al., 2008 (EARLY) (3)	Bosentan 125 mg bid	Conventional therapy	93	45.2	76.3	II [100]	24	IPAH [61], APAH [39]	LIVER, Edema
	Placebo		92	44.2	63.0
McLaughlin et al., 2015 (COMPASS-2) (21)	Bosentan 125 mg bid	Sidenafil	159	52.9	78.6	I [42]	16	IPAH [68], APAH [32]	LIVER, Anemia, Edema
						II [58]
	Placebo		174	54.7	73.1	IV [<1]
Galiè et al., 2008(ARIES-1) (4)	Ambrisentan 5 mg qd	Conventional therapy	67	53.0	83.6	I [2]	12	IPAH [63], APAH [37]	LIVER, Edema
						II [32]
	Ambrisentan 10 mg qd		67	49.0	79.1	III [58]
	Placebo		67	48.0	88.1	IV [8]
Galiè et al., 2008 (ARIES-2) (4)	Ambrisentan 2.5 mg qd	Conventional therapy	64	52.0	75.0	I [2]	12	IPAH [65], APAH [35]	LIVER, Edema
	Ambrisentan 5 mg qd		63	50.0	81.0	II [45]
	Placebo		65	51.0	67.7	III [52]
						IV [1]
Galiè et al., 2015 (AMBITION) (22)	Ambrisentan 10 mg qd + Tadalafil	Conventional therapy	253	54.5	74.0	II [31]	24	IPAH [59], APAH [41]	Edema, Anemia
	Tadalafil + Placebo		121	54.5	83.0	III [69]
Pulido et al., 2013 (SERAPHIN) (5)	Macitentan 3 mg qd	Prostanoids, PDE5, or no	250	44.5	75.4	II [52]	24	IPAH [56], APAH [44]	LIVER, Edema, Anemia
	Macitentan 10 mg qd		242	45.5	80.2	III [46]
	Placebo		249	46.7	73.9	IV [2]

N, number of patients; WHO FC, World Health Organization functional class; IPAH, idiopathic pulmonary arterial hypertension (includes familial or hereditary hypertension, or pulmonary arterial hypertension due to drug or toxins and anorexigens); APAH, associated pulmonary arterial hypertension(includes pulmonary arterial hypertension due to connective tissue disease, congenital heart disease, human immunodeficiency virus infection, and portal hypertension); LIVER, abnormal liver function; BREATHE, bosentan randomized trial of endothelin antagonist therapy; EARLY, endothelin antagonist trial in mildly symptomatic pulmonary hypertension patients; COMPASS-2, effect of combination of bosentan and sildenafil versus sildenafil monotherapy on morbidity and mortality in symptomatic patients with pulmonary arterial hypertension; ARIES, ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy study; AMBITION, the ambrisentan and tadalafil in patients with pulmonary arterial hypertension; SERAPHIN, study with an endothelin receptor antagonist in pulmonary hypertension to improve clinical outcome; NA, not available; PDE5, phosphodiesterase type 5 inhibitors.