Adding inhaled iloprost to bosentan monotherapy in PAH patients improved 6-minute walk distance by a placebo-adjusted 26 m (p=0.051) and significantly improved NYHA functional class (p=0.002).
RCT (n=67)
double-blind
randomized
Yes
Does adding inhaled iloprost to bosentan improve exercise capacity and clinical outcomes in patients with pulmonary arterial hypertension?
Adding inhaled iloprost to bosentan monotherapy in PAH patients safely improves exercise capacity, functional class, and hemodynamics.
Effect estimate: Difference +26 m
Absolute Event Rate: 30% vs 4%
p-value: p=0.051
Abstract Rationale Small, open-label studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension (PAH). Objective To evaluate the safety and efficacy of adding inhaled iloprost, a prostacyclin analog, to the endothelin receptor antagonist bosentan in patients with PAH. Methods In a randomized, multicenter, double-blind trial, inhaled iloprost (5 μg) or placebo was added to stable monotherapy with bosentan for 12 wk. Efficacy endpoints included change from baseline in 6-min-walk distance (6-MWD), modified New York Heart Association (NYHA) functional class, hemodynamic parameters, and time to clinical worsening. Measurements and Main Results A total of 67 patients with PAH (55% idiopathic PAH, 45% associated PAH, 94% NYHA class III, and mean baseline 6-MWD of 335 m) were randomized. At Week 12, patients receiving iloprost had a mean increase in 6-MWD of 30 m (p = 0.001); placebo patients had a mean 6-MWD increase of 4 m (p = 0.69), with a placebo-adjusted difference of +26 m (p = 0.051). NYHA status improved by one class in 34% of iloprost versus 6% of placebo patients (p = 0.002). Iloprost delayed the time to clinical worsening (p = 0.0219). Improvements were noted in postinhalation placebo-adjusted change in mean pulmonary artery pressure (−8 mm Hg; p 0.001) and pulmonary vascular resistance (−254 dyn · s · cm−5; p 0.001). Combination therapy was well tolerated. Conclusions Within the limitations of a relatively small sample size, results of this study demonstrate that the addition of inhaled iloprost in patients with PAH with reduced exercise capacity on bosentan monotherapy is safe and efficacious.
McLaughlin et al. (Thu,) conducted a rct in Pulmonary arterial hypertension (n=67). inhaled iloprost vs. placebo was evaluated on Change from baseline in 6-min-walk distance (6-MWD) (Difference +26 m, p=0.051). Adding inhaled iloprost to bosentan monotherapy in PAH patients improved 6-minute walk distance by a placebo-adjusted 26 m (p=0.051) and significantly improved NYHA functional class (p=0.002).