Why the study?
The efficacy of oral selexipag compared to parenteral prostacyclin analogues in pulmonary arterial hypertension patients already on double-combination therapy with an ERA and PDE5-I was unknown.
Does oral selexipag compared to parenteral treprostinil or epoprostenol improve exercise capacity and hemodynamics differently in PAH patients on background double-combination therapy?
Does oral selexipag compared to parenteral treprostinil or epoprostenol improve exercise capacity and hemodynamics differently in PAH patients on background double-combination therapy?
In PAH patients on double-combination therapy, parenteral prostacyclin analogues (treprostinil, epoprostenol) are typically used in younger, more severe patients and yield stronger hemodynamic and exercise improvements compared to oral selexipag.
May support preferring parenterals over selexipag for greater gains in severe PAH on double therapy; leaves open confounding by indication.
Background The event-driven, phase 3, randomized, double-blind, placebo-controlled GRIPHON trial demonstrated that Selexipag reduces the risk of a composite end point of death or morbidity events in pulmonary arterial hypertension (PAH). Despite the advantage of a per os formulation, its efficacy in comparison to parenteral prostacyclin analogues in patients already on double-combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5-I) is unknown. Purpose We compared the effects of Selexipag (S) vs subcutaneous Treprostinil (T) vs intravenous Epoprostenol (E) in PAH patients on both ERA and PDE5-I. Methods We enrolled on double combination therapy starting S, T or E and with a complete hemodynamic re-evaluation 3-6 months after reaching the maximal drug dose. S, T or E were gradually uptitrated to the maximum tolerated/approved dose. We systematically assessed WHO-functional class (FC), 6-minute walk distance (6MWD) and right heart catheterization before treatment and 3-6 months after reaching a stable drug dose. With Dunn’s test, we compared changes in WHO-FC, 6MWD and haemodynamic parameters. Results Two hundred and three patients with PAH were enrolled. Results are shown in the Table. Conclusions S was prescribed to the oldest and least severe PAH patients, while T and E to the youngest and most severe PAH patients and led to a stronger improvement of exercise capacity and haemodynamic profile.
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Ballerini et al. (2025) studied this question.
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