Table 3.
Details of included combination therapy RCTs*
| Reference | Barst 2011 (PHIRST-1) | Simonneau 2008 (PACES) | McLaughlin 2006 (STEP) | Humbert 2004 (BREATHE-2) | ||||
|---|---|---|---|---|---|---|---|---|
| Baseline therapy | ERA | Pr (iv epo) | ERA | None | ||||
| Add-on therapy | PDE5i | Placebo | PDE5i | Placebo | Pr (inh ilp) | Placebo | ERA | ERA+ Pr (iv epo) |
| Treatment dose | 40 mg tadalafil once daily | 3x20mg sildenafil daily, increased to 40 and 80 at 4 week intervals | 5 μg inhaled iloprost | 62.5 mg bosentan twice daily, increased to 125 mg twice daily after 4 weeks. Intravenous epoprostenol started at 2 ng/kg/min and increased up to 14 ± 2 ng/kg/min after 16 weeks. | ||||
| Patients at end of trial | 42 | 45 | 133 | 123 | 34 | 33 | 19 | 10 |
| Duration | 16 weeks | 16 weeks | 12 weeks | 16 weeks | ||||
| Change 6MWD | 40.2 (8.5) | 18.8 (9.2) | 29.8 (5.3) | 1 (5.3) | 30 (10.3) | 4 (10.6) | 72 (11.47) | 46 (19.61) |
| Baseline 6MWD | 360.9 (11.6) | 348.5 (12.7) | 348.9 (6.2) | 341 (6.7) | 331 (73) | 340 (64) | 323.04§ | 323.62§ |
| Age | 50 | 51.7 | 47.8 | 47.5 | 49 | 51 | 45 | 47 |
| Sex (% male) | 0.21 | 0.22 | 0.18 | 0.23 | 0.21 | 0.21 | 0.23 | 0.45 |
| STATUS | 2.5 | 2.7 | 2.8 | 2.8 | 3.0 | 3.0 | 3.23 | 3.27 |
| PVR | 863.3 | 863.3 | 856.8 | 754.9 | 815 | 783 | 1511 | 1426 |
*E are endothelin receptor antagonists, P5 are phosphodiesterase 5 inhibitors, Pr are prostacyclin analogues. iv ep is intravenous epoprostenol, inh ilp is inhaled iloprost.
§Imputed based on linear model for baseline 6MWD with covariates for Age, Sex, mean STATUS, and mean right arterial pressure.