Table 1

Summary of included studies evaluating treatment with PAH agents in patients with all forms of PAH

Source (official acronym)PAH agentNumber of patientsNumber (%) of CTD-PAH patientsStudy designInterventionControlPeriod (weeks)Results for CTD-PAH
Galiè et al15 (SUPER-1)Sildenafil27884 (30)RCT, DB20 mg×3/day, 40 mg×3/day and 80 mg×3/dayPlacebo12Available in Badesch et al34
Singh et al16Sildenafil200RCT, DB25 mg on first day, then if no hypotension, 100 mg×3/dayPlacebo6None
Simonneau et al17 (PACES)Sildenafil26755 (21)RCT, DB20 mg×3/day, titrated to 40 mg and 80 mg×3/day, as tolerated, at 4-week intervals on background treatment with epoprostenolPlacebo on background treatment with epoprostenol16None
Galiè et al18 (PHIRST)Tadalafil40595 (24)RCT, DB2.5, 10, 20 and 40 mgPlacebo16Available in this article
Channick et al19Bosentan325 (16)RCT, DB62.5 mg×2/day for 4 weeks, then 125 mg×2/dayPlacebo12Available in Denton et al. (2006)35
Rubin et al20 (BREATHE-1)Bosentan21363 (30)RCT, DB62.5 mg×2/day for 4 weeks, then 125 mg or 250 mg×2/dayPlacebo16Available in Denton et al35
Galiè et al21 (BREATHE-5)Bosentan540RCT, DB62.5 mg×2/day for 4 weeks, then 125 mg×2/dayPlacebo16None
Galiè et al22 (EARLY)Bosentan18533 (18)RCT, DB62.5 mg×2/day for 4 weeks, then 125 mg×2/dayPlacebo24None
Galiè et al23 (ARIES)Ambrisentan393124 (32)RCT, DB2.5, 5 and 10 mgPlacebo12Available in Badesch37
Rubin et al24Epoprostenol230RCT, open-labelInitial dosage of 1–2 ng/kg/min, then titrated to an optimal doseConventional therapy8None
Barst et al25Epoprostenol810RCT, open-labelInitial dosage of 2 ng/kg/min, then titrated to optimal dosageConventional therapy12None
Badesch et al26Epoprostenol111111 (100)RCT, open-labelDosage established according to signs and symptoms from an initial low doseConventional therapy12Available in this article
Galiè et al27 (ALPHABET)Beraprost13013 (10)RCT, DB20 mg×4/day for first week, then titrated to 120 mg×4/dayPlacebo12None
McLaughlin et al28 (STEP)Inhaled iloprost67NRRCT, DB5 mg on background treatment with bosentan (125 mg×2/day)Placebo on background treatment with bosentan (125 mg×2/day)12None
Hoeper et al29 (COMBI)Inhaled iloprost400RCT, open-label5 mg on background treatment with bosentan (125 mg×2/day)Placebo on background treatment with bosentan (125 mg×2/day)12None
Simonneau et al30Treprostinil46990 (19)RCT, DBInitial dosage of 1.25 ng/kg/min, then titrated to maximum dosage of 22.5 ng/kg/minPlacebo12None
McLaughlin et al31Treprostinil260RCT, DBInitial dosage of 2.5 or 5.0 ng/kg/min, then titrated to maximum dosage of 20 ng/kg/minPlacebo8Available in Oudiz et al40
McLaughlin et al32Treprostinil2350RCT, DBInitiated at 3 breaths (18 mg)/inhalation, then titrated to maximum dosage of 9 breaths (54 mg) at each of the 4 daily dosesPlacebo12None
Hiremath et al33Treprostinil442 (5)RCT, DBInitial dose of 4 ng/kg/min, then titrated to maximum dose of 100 ng/kg/minPlacebo12None
  • CTD, connective tissue disease; DB, double-blind; NR, not reported; PAH, pulmonary arterial hypertension; RCT, randomised controlled trial.