Table 1. Summary of the major trials of disease-targeted therapy in congenital heart disease (CHD)-associated pulmonary arterial hypertension.

First author [Ref.]	Year	Drug	Study design	Patients n	Patients with CHD %	NYHA class	Mean age yrs	Outcome#	Change in 6MWT m	Follow-up period
Christensen [28]	2004	Bosentan	Retrospective	9	100	III/IV	47	NA	Not reported	9.5 months
Schulze-Neick [29]	2005	Bosentan	Open label, prospective	33	100	II-IV	43	Functional class 6MWT Haemodynamics	77	2.1 yrs
Gatzoulis [30]	2005	Bosentan	Open label, prospective	10¶	100	III	42	O2 saturation 6MWT	99	3 months
Galie [27]	2006	Bosentan	Randomised, double-blind, placebo controlled	54	100	III	37 (treatment arm)	PVR	43	16 weeks
Kotlyar [31]	2006	Bosentan	Retrospective	23¶	100	II-IV	37	NA	0	15 months
Benza [32]	2006	Bosentan	Retrospective	24	100	II-IV	50	NA	31	1 yr
Sitbon [33]	2006	Bosentan	Retrospective	27	100	III/IV	35	NA	66	15 months
D'Alto [34]	2007	Bosentan	Open label, prospective	22	100	II-IV	38	Functional class Haemodynamics 6MWT O2 saturation	67	1 yr
Apostolopoulou [35]	2007	Bosentan	Open label, prospective	18	100	II-IV	22	O2 saturation 6MWT Functional class Peak exercise capacity	0	2 yrs
Diller [36]	2007	Bosentan	Retrospective	18	100	III	41	NA	124	29 months
Van Loon [37]	2007	Bosentan	Retrospective	20	100	II-IV	39	NA	0	2.1 yrs (median)
Gatzoulis [38]	2008	Bosentan	Open label extension of BREATHE-5	37¶	100%	III	40	6MWT Functional class	61	40 weeks
Barst [39]	2004	Sitaxsentan 100 mg and 300 mg	Randomised, double-blind, placebo controlled	178	24	II-III	46	Peak V′O2	35 (100 mg) 33 (300 mg)	12 weeks
Barst [40]	2006	Sitaxsentan 50 mg and 100 mg	Randomised, double-blind, placebo controlled	245	11	II-IV	54	6MWT	24 (50 mg) 31 (100 mg)	18 weeks
Singh [41]	2006	Sildenafil 300 mg	Randomised, double-blind crossover, placebo controlled	10¶	100	II-IV	Median 15 (4–35)	6MWT	97	12 weeks
Chau [42]	2007	Sildenafil 150 mg	Prospective open label	7¶	100	Mean 3.3	37	Functional class O2 saturation Haemodynamics 6MWT	NS 28†	6 months
Garg [43]	2007	Sildenafil 300 mg	Prospective, open label	44	48	II/III	26	Functional class O2 saturation Haemodynamics 6MWT	119	19 months
Tay [44]	2010	Sildenafil 60 mg·day−1	Prospective open label	12	100	III	34	Quality of life O2 saturation 6MWT	45	3 months
Mukhopadhyay [45]	2006	Tadalafil	Observational, prospective	16¶	100	II/III	25	Functional class O2 saturation Haemodynamics 6MWT	43	12 weeks
Galie [46]	2009	Tadalafil	Randomised, double-blind, placebo-controlled	405	12	II-IV	53	6MWT	33	16 weeks
Rosenzweig [47]	1999	Epoprostenol i.v.	Retrospective	20	100	II-IV	15	NA	52	1 yr
Fernandes [48]	2003	Epoprostenol i.v.	Retrospective	8	100	III/IV	Median 37 (15–57)	NA	299	3 months
Simonneau [49]	2002	Treprostinil s.c. max dose 22.5 ng·kg−1·min−1	Randomised, double-blind, placebo-controlled	470	23	II-IV	44	6MWT	16	12 weeks
Tapson [50]	2006	Treprostinil i.v. mean dose 41 ng·kg−1·min−1	Prospective, open label	16	13	III/IV	45	6MWT Functional class Haemodynamics	82	12 weeks
Lang [51]	2006	Treprostinil s.c. mean dose 40 ng·kg−1·min−1	Retrospective	99	23	II-IV	47	NA	139	26 months

Drugs were administered orally unless otherwise stated. If trials differed in drug doses, these are specified. Studies that were not entirely comprised of patients with CHD are those by Barst [39, 40], Garg [43], Galie [46], Simonneau [49], Tapson [50] and Lang [52]. BREATHE-5: Bosentan Randomised trial of Endothelin Antagonist THErapy-5; NYHA: New York Heart Association; NA: not applicable; 6MWT: 6-min walk test; PVR: pulmonary vascular resistance; V′_O2: oxygen uptake; NS: not statistically significant. ^#: primary outcome only in randomised controlled trials; ^¶: all Eisenmenger; ^†: actual class not specified.