Summary of included studies evaluating treatment with PAH agents in patients with all forms of PAH
| Source (official acronym) | PAH agent | Number of patients | Number (%) of CTD-PAH patients | Study design | Intervention | Control | Period (weeks) | Results for CTD-PAH |
|---|---|---|---|---|---|---|---|---|
| Galiè et al15 (SUPER-1) | Sildenafil | 278 | 84 (30) | RCT, DB | 20 mg×3/day, 40 mg×3/day and 80 mg×3/day | Placebo | 12 | Available in Badesch et al34 |
| Singh et al16 | Sildenafil | 20 | 0 | RCT, DB | 25 mg on first day, then if no hypotension, 100 mg×3/day | Placebo | 6 | None |
| Simonneau et al17 (PACES) | Sildenafil | 267 | 55 (21) | RCT, DB | 20 mg×3/day, titrated to 40 mg and 80 mg×3/day, as tolerated, at 4-week intervals on background treatment with epoprostenol | Placebo on background treatment with epoprostenol | 16 | None |
| Galiè et al18 (PHIRST) | Tadalafil | 405 | 95 (24) | RCT, DB | 2.5, 10, 20 and 40 mg | Placebo | 16 | Available in this article |
| Channick et al19 | Bosentan | 32 | 5 (16) | RCT, DB | 62.5 mg×2/day for 4 weeks, then 125 mg×2/day | Placebo | 12 | Available in Denton et al. (2006)35 |
| Rubin et al20 (BREATHE-1) | Bosentan | 213 | 63 (30) | RCT, DB | 62.5 mg×2/day for 4 weeks, then 125 mg or 250 mg×2/day | Placebo | 16 | Available in Denton et al35 |
| Galiè et al21 (BREATHE-5) | Bosentan | 54 | 0 | RCT, DB | 62.5 mg×2/day for 4 weeks, then 125 mg×2/day | Placebo | 16 | None |
| Galiè et al22 (EARLY) | Bosentan | 185 | 33 (18) | RCT, DB | 62.5 mg×2/day for 4 weeks, then 125 mg×2/day | Placebo | 24 | None |
| Galiè et al23 (ARIES) | Ambrisentan | 393 | 124 (32) | RCT, DB | 2.5, 5 and 10 mg | Placebo | 12 | Available in Badesch37 |
| Rubin et al24 | Epoprostenol | 23 | 0 | RCT, open-label | Initial dosage of 1–2 ng/kg/min, then titrated to an optimal dose | Conventional therapy | 8 | None |
| Barst et al25 | Epoprostenol | 81 | 0 | RCT, open-label | Initial dosage of 2 ng/kg/min, then titrated to optimal dosage | Conventional therapy | 12 | None |
| Badesch et al26 | Epoprostenol | 111 | 111 (100) | RCT, open-label | Dosage established according to signs and symptoms from an initial low dose | Conventional therapy | 12 | Available in this article |
| Galiè et al27 (ALPHABET) | Beraprost | 130 | 13 (10) | RCT, DB | 20 mg×4/day for first week, then titrated to 120 mg×4/day | Placebo | 12 | None |
| McLaughlin et al28 (STEP) | Inhaled iloprost | 67 | NR | RCT, DB | 5 mg on background treatment with bosentan (125 mg×2/day) | Placebo on background treatment with bosentan (125 mg×2/day) | 12 | None |
| Hoeper et al29 (COMBI) | Inhaled iloprost | 40 | 0 | RCT, open-label | 5 mg on background treatment with bosentan (125 mg×2/day) | Placebo on background treatment with bosentan (125 mg×2/day) | 12 | None |
| Simonneau et al30 | Treprostinil | 469 | 90 (19) | RCT, DB | Initial dosage of 1.25 ng/kg/min, then titrated to maximum dosage of 22.5 ng/kg/min | Placebo | 12 | None |
| McLaughlin et al31 | Treprostinil | 26 | 0 | RCT, DB | Initial dosage of 2.5 or 5.0 ng/kg/min, then titrated to maximum dosage of 20 ng/kg/min | Placebo | 8 | Available in Oudiz et al40 |
| McLaughlin et al32 | Treprostinil | 235 | 0 | RCT, DB | Initiated at 3 breaths (18 mg)/inhalation, then titrated to maximum dosage of 9 breaths (54 mg) at each of the 4 daily doses | Placebo | 12 | None |
| Hiremath et al33 | Treprostinil | 44 | 2 (5) | RCT, DB | Initial dose of 4 ng/kg/min, then titrated to maximum dose of 100 ng/kg/min | Placebo | 12 | None |
CTD, connective tissue disease; DB, double-blind; NR, not reported; PAH, pulmonary arterial hypertension; RCT, randomised controlled trial.