Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension.

Background: Tadalafil 40 mg orally once daily, was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week, double-blind, placebo (PBO)-controlled trial. Inclusion criteria included the option for background bosentan. Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified. Objectives were to provide safety and efficacy data for both groups. Methods: Groups analyzed included: treatment-naive + PBO; treatment-naive + tadalafil; background bosentan + PBO; and background bosentan + tadalafil. Patients randomized to tadalafil or PBO (N = 405) were analyzed by bosentan use (yes = 216, no = 189). Treatment differences in 6-minute walk distance (6MWD, PBO-adjusted), functional class (FC), clinical worsening (CW) and adverse events were assessed. Hazard ratios (HRs) with 95% confidence intervals (CIs) are presented for FC and CW. Results: At Week 16, PBO-adjusted 6MWD increases were 44 m (CI: 20 to 69 m; n = 37) for tadalafil 40 mg in treatment-naive patients and 23 m (CI: -2 to 48 m; n = 42) for tadalafil 40 mg add-on to bosentan. The 6MWD for treatment-naive and background bosentan PBO patients decreased by 3 m and increased by 19 m, respectively, at Week 16 compared with baseline. Two (5%) treatment-naive patients had CW with tadalafil 40 mg vs 8 (22%) with PBO (HR = 3.3, CI: 1.1 to 10.0). Two (5%) background bosentan patients had CW with tadalafil 40 mg add-on vs 5 (11%) for PBO add-on (HR = 1.9, CI: 0.4 to 10.2). Adverse events for tadalafil monotherapy and as add-on were similar. Conclusion: Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy. It was also well-tolerated when added to background bosentan, but data are insufficient to conclude additional benefit