TY - JOUR T1 - Early selexipag initiation and long-term outcomes: insights from randomised controlled trials in pulmonary arterial hypertension JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00456-2022 VL - 9 IS - 1 SP - 00456-2022 AU - J. Gerry Coghlan AU - Sean Gaine AU - Richard Channick AU - Kelly M. Chin AU - Camille du Roure AU - J. Simon R. Gibbs AU - Marius M. Hoeper AU - Irene M. Lang AU - Stephen C. Mathai AU - Vallerie V. McLaughlin AU - Lada Mitchell AU - Gérald Simonneau AU - Olivier Sitbon AU - Victor F. Tapson AU - Nazzareno Galiè Y1 - 2023/01/01 UR - http://openres.ersjournals.com/content/9/1/00456-2022.abstract N2 - Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. Post hoc analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit versus initial double combination on haemodynamic and functional parameters in TRITON. Post hoc analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort. Data from newly diagnosed (≤6 months) PAH patients from GRIPHON and TRITON were pooled. Patients on active therapy with selexipag (pooled selexipag group) were compared with those on control therapy with placebo (pooled control group). Disease progression end-points were defined as per the individual studies. Hazard ratios (HR) and 95% CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo) +7 days and time to all-cause death up to end of study were estimated using Cox regression models. The pooled dataset comprised 649 patients, with 44% on double background therapy. Selexipag reduced the risk of disease progression by 52% versus control (HR: 0.48; 95% CI: 0.35–0.66). HR for risk of all-cause death was 0.70 (95% CI: 0.46–1.10) for the pooled selexipag versus control group. Sensitivity analyses accounting for the impact of PAH background therapy showed consistent results, confirming the appropriateness of data pooling. These post hoc, pooled analyses build on previous insights, further supporting selexipag use within 6 months of diagnosis, including as part of triple therapy, to delay disease progression.This post hoc pooled analysis of GRIPHON and TRITON patients with a diagnosis of ≤6 months suggests that early targeting of the prostacyclin pathway with selexipag may be beneficial in delaying disease progression in a broad PAH population https://bit.ly/3CocEBe ER -