Randomized study of adding tadalafil to existing ambrisentan in pulmonary arterial hypertension

Abstract

This prospective, double-blinded, randomized controlled study aimed to investigate the efficacy and safety of oral tadalafil in patients receiving background ambrisentan therapy. Current treatments for pulmonary arterial hypertension (PAH) remain insufficient, resulting in high mortality rates. The addition of oral tadalafil, a phosphodiesterase-5 inhibitor, to background ambrisentan may provide a safe and effective therapeutic strategy. A total of 124 patients who had been treated with ambrisentan for at least 4 months and had a stable 6-min walking distance (6MWD) and World Health Organization (WHO) functional class (FC) for at least 1 month were randomized to either the oral tadalafil or placebo group. Treatment differences in 6MWD, changes in FC, clinical worsening (CW) and adverse events were analyzed after 16 weeks of treatment. At week 16, the tadalafil group showed a significantly improved exercise capacity as assessed by the 6MWD (P<0.05). In addition, 5 (8.3%) patients receiving tadalafil add-on therapy had CW vs. 15 (23.4%) with placebo (P<0.05). No significant differences were found in adverse events or changes in hemodynamic parameters between the placebo and tadalafil groups. Tadalafil 40 mg was well-tolerated as add-on therapy to background ambrisentan. However, the data from this study are insufficient to prove the additional therapeutic benefits of tadalafil add-on therapy. © 2014 The Japanese Society of Hypertension.