Randomised controlled trials with endothelin receptor antagonists in pulmonary arterial hypertension
| Drug | First author [Ref.] | Subjects n | Dose | Duration weeks | Primary end-point(s) | Significantly improved? | Additional results |
| Ambrisentan | Galie [47] | 64 | 1, 2.5, 5 or 10 mg q.d. | 12 | 6MWD | Yes (versus baseline) | Improved HD (P̄pa, PVR, CI), BDI, patient global assessmentNo effect P̄ra |
| Galie [48] | 201 | 5 or 10 mg q.d. | 12 | 6MWD | Yes | Improved WHO FC, BDINo effect on TCW, SF-36Decreased BNP | |
| Galie [48] | 192 | 2.5 or 5 10 mg q.d. | 12 | 6MWD | Yes | Improved TCW, SF-36, BDINo effect WHO FCDecreased BNP | |
| Bosentan | Channick [46] | 32 | 62.5 mg b.i.d. for 4 weeks then 125 mg b.i.d. | 12 | 6MWD | Yes | Improved TCW, BDI, WHO FC, HD (P̄pa, PVR, CI, Ppcw, P̄ra) |
| Rubin [49] | 213 | 62.5 mg b.i.d. for 4 weeks then 125 or 250 mg b.i.d. | 16 | 6MWD | Yes | Improved BDI, TCW | |
| Galie [50] | 54 | 62.5 mg b.i.d. for 4 weeks then 125 mg b.i.d. | 16 | Sp,O2, PVR index | Noninferior¶, yes | Improved 6MWD, HD (P̄pa, P̄sa)No effect HD (P̄ra, others) | |
| Galie [51] | 168 (PVR) 177 (6MWD) | 62.5 mg b.i.d. for 4 weeks then 125 mg b.i.d. | 24 | PVR, 6MWD | Yes, no | Improved TCW, SF-36, HD (P̄pa, CI, mixed venous Sa,O2)Decreased BNPNo effect P̄ra | |
| Sitaxentan | Barst [52] | 178 | 100 or 300 mg q.d. | 12 | Peak V′O2 | Yes (300 mg), no (100 mg) | Improved 6MWD, NYHA FC, HD (PVR, CI, P̄pa (300 mg))No effect CPET, TCW |
| Barst [53] | 245# | 50 or 100 mg q.d. | 18 | 6MWD | Yes (100 mg), no (50 mg) | Improved WHO FC (100 mg)No effect TCW, BDI |
PVR: pulmonary vascular resistance; 6MWD: 6-min walk distance; Sp,O2: arterial oxygen saturation measured by pulse oximetry; V′O2: oxygen uptake; HD: haemodynamics; P̄pa: mean pulmonary arterial pressure; CI; cardiac index; BDI: Borg dyspnoea index; P̄ra: mean right atrial pressure; WHO: World Health Organization; FC: functional class; TCW: time to clinical worsening; SF-36: Short Form-36; BNP: B-type natriuretic peptide; Ppcw: pulmonary capillary wedge pressure; P̄sa: mean systemic arterial pressure; Sa,O2: arterial oxygen saturation; NYHA: New York Heart Association; CPET: cardiopulmonary exercise testing. #: including patients in an open-label bosentan arm; ¶: bosentan was noninferior to placebo with respect to worsening Sp,O2.