Patients with collagen vascular disease (CVD)-associated pulmonary arterial hypertension (PAH) have a poorer prognosis than other PAH patients. Tadalafil, a competitive inhibitor of phosphodiesterase 5 (PDE5), appeared safe and efficacious for PAH in a 16-week, double-blind, placebo controlled trial. We describe results in patients with CVD during the 16-week trial and a blinded extension trial.
Study patients were randomized to placebo or 2.5, 10, 20 or 40 mg tadalafil (n = 16, 15, 22, 19 and 17, respectively) and efficacy was assessed by measures including six-minute walk test (primary endpoint) and clinical worsening (death, lung transplantation, atrial septostomy, new chronic PAH treatment, worsening WHO functional class or hospitalization for worsening PAH) at Week 16, compared to baseline. Patients on 20 mg at Week 16 continued on this dose; all others received 40 mg long term.
For all tadalafil-treated subjects with CVD-associated PAH, the median change in 6MW was numerically higher compared to placebo (median range 4.1 to 27.0 meters; mean range 2.6 to 31.7 meters) at Week 16. The median change in the tadalafil 40 mg group (22.0 meters) reached statistical significance (p < 0.05). The percentage of patients with worsening at Week 16 was numerically lower in the tadalafil groups (19%, 13%, 10% and 11% for the 2.5, 10, 20 and 40 mg groups), compared to placebo (25%).CVD patients experienced worsening at a slightly higher rate than patients with PAH etiologies of “other” or “idiopathic” during the long-term study. At Week 52, 20% of patients with CVD-associated PAH had worsened, compared to 16% of idiopathic PAH and 9% of patients with other PAH. The most common adverse event in these patients was headache.
Tadalafil appeared to improve 6MW and decrease clinical worsening, compared to placebo, over a 16-week treatment period in CVD-associated PAH. These patients had a slightly higher rate of clinical worsening events during a 52-week extension trial.
Tadalafil is potentially useful in the treatment of CVD-associated PAH.
Reda Girgis, Consultant fee, speaker bureau, advisory committee, etc. Consultant: Actelion, Gilead, United TherapeuticsClinical Research Support: Pfizer, United Therapeutics, Lilly-ICOS, ActelionMichael Wade and Carl Arneson are employees of United Therapeutics Corp.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Tadalafil is not yet approved