Systematic review of randomised, double-blind clinical trials of oral agents conducted in patients with pulmonary arterial hypertension

Background: Therapies have become available in the last decade that may provide more than symptomatic benefit in patients with pulmonary arterial hypertension (PAH). With choices for possible therapy, it is important to compare the results observed in randomised, double-blind clinical trials. The objective of this systematic review was to compare the published results for the different oral therapeutic agents for the treatment of PAH. Methods: US Food and Drug Administration-approved agents, as well as agents for which a New Drug Application has been submitted, were included in this review. Fifteen randomised, double-blind studies (one study examined both sildenafil and bosentan) were found for the different oral agents: sildenafil, four studies; bosentan, six studies; sitaxsentan, three studies; and ambrisentan, three studies. Most randomised, double-blind studies conducted in patients with PAH have been small (< 100 patients overall) and of short duration (12 or 16 weeks). Results: In the clinical trials, all oral therapeutic agents improved exercise ability as measured by the 6-min walk distance; however, other clinically relevant end-points were not improved consistently by all agents, e.g. time to clinical worsening and WHO functional class.