Initial Triple Oral Therapy in Pulmonary Arterial Hypertension (PAH): Extended Long-Term Outcome Data from TRITON

Purpose In TRITON (NCT02558231), initial triple (macitentan, tadalafil, selexipag) and initial double (macitentan, tadalafil, placebo) oral therapy in newly diagnosed PAH patients markedly improved hemodynamic and functional parameters at week 26, with no difference between groups. Main analysis up to end of main observation period suggested that initial triple therapy reduced the risk of disease progression vs initial double therapy. Here, we present data from a longer follow-up period (up to end of study [EOS]). Methods In this multicenter, double-blind, randomized, placebo-controlled, phase 3b study, end of the main observation period occurred when the last patient randomized completed week 26. Unblinding occurred after end of main observation period, and patients were further followed-up to EOS, which occurred 30 days after last intake of study treatment. Time to first disease progression event (pre-specified) and all-cause death (post-hoc) were analyzed with Cox regression; all disease progression events were analysed (post-hoc) using a negative binomial model. Events were centrally adjudicated in a blinded fashion. Results Median follow-up time at EOS was 100 weeks in the initial triple therapy group (n=123) and 95 weeks in the initial double therapy group (n=124) (Table). The hazard ratio for the risk of a first disease progression event and the rate of all disease progression events for initial triple vs initial double therapy were similar at end of main observation period and at EOS (Table). Four patients in the initial triple and 12 in the initial double therapy groups died before EOS. Safety up to EOS was consistent with findings at end of main observation period. Conclusion Results at EOS and at end of main observation period are consistent and suggest a signal for improved long-term outcome with initial triple vs initial double oral therapy.