Long-term outcomes in newly diagnosed pulmonary arterial hypertension (PAH) patients receiving initial triple oral combination therapy: insights from the randomised controlled TRITON study

Abstract

Abstract Introduction Long-term outcomes are important in PAH. Purpose To evaluate the long-term efficacy and safety of initial triple oral therapy with selexipag, macitentan and tadalafil vs initial double oral therapy with macitentan and tadalafil in PAH. Methods TRITON, a multicentre, double-blind, placebo-controlled, phase 3b study, randomised 1:1 newly diagnosed, treatment-naïve PAH patients to initial triple vs double therapy. Macitentan and tadalafil were initiated at randomisation and selexipag/placebo at day 15 (uptitrated to wk 12). Efficacy and safety were assessed in a blinded manner until the last patient randomised completed wk 26 (end of observation period). Pulmonary vascular resistance (PVR; primary endpoint) and 6-minute walk distance (6MWD) were assessed at wk 26. Other secondary endpoints included time to first disease progression event (centrally adjudicated) to end of observation period +7 days. Time to all-cause mortality up to end of observation period was analysed post-hoc. Results 247 patients were randomised to initial triple (n=123) or initial double therapy (n=124); baseline characteristics were balanced between groups. Median follow-up was 77.6 (initial triple) and 75.8 wks (initial double). Initial triple and initial double therapy improved PVR (by 54% and 52%) and 6MWD (by 55 and 56 m), with no difference between groups. A 41% reduction in the risk of first disease progression event driven by PAH-related hospitalisation and all-cause death was observed with initial triple vs initial double therapy (hazard ratio 0.59, 95% CI 0.32–1.09, p=0.087; Figure). Two patients died in the initial triple vs 9 in the initial double therapy group (hazard ratio 0.23, 95% CI 0.05–1.04). Adverse events were consistent with the known safety profiles of the study drugs. Conclusions In TRITON, assessments at wk 26 showed marked improvements in both treatment arms, with no difference between groups. Exploratory analysis indicated a signal for improved long-term outcome with initial triple versus initial double therapy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd.