Effectiveness and persistence with selexipag in pulmonary arterial hypertension in the real-life setting

The prostanoid analog epoprostenol, the first approved targeted therapy for pulmonary arterial hypertension (PAH), is also the only one that has shown any benefit for survival vs. placebo in PAH patients [ ]. However, its complex route of administration (continuous intravenous infusion) and potentially serious administration-related side effects have limited its use in clinical practice [ , ]. Subsequent prostanoid analogs have had a limited use due to the pain associated with infusion (treprostinil, subcutaneous), frequent dosing (iloprost, inhaled), and prostanoid-associated side effects [ ]. Given the relevance of targeting the prostacyclin pathway for PAH management, developing ways of enabling more convenient administration has been considered an urgent need [ ]. Selexipag is a first-in-class orally available selective IP prostacyclin receptor agonist with a more convenient administration. In the event-driven Phase 3 GRIPHON clinical trial, selexipag significantly reduced the risk of the composite endpoint of death or a PAH-related complication vs. placebo [ ]. Selexipag has been available since the mid-2010s and is currently the only drug targeting the prostacyclin pathway that is recommended in intermediate/low-risk patients while receiving oral therapies [ ]. Given the relatively short experience with selexipag, real-world evidence is of interest to fully understand its role in PAH treatment. The Spanish Pulmonary Arterial Hypertension Registry (REHAP) has been running in Spain since 2007, having also retrospectively collected information on PAH patients since 1998 [ ]. Using data from REHAP patients enrolled between July the 1st 2007 and December the 31st 2021 (N = 3076) who had received selexipag as their first prostacyclin either as monotherapy or in combination (N = 135; 4.4%), we have analyzed the pattern of use and the effectiveness of selexipag in terms of survival and treatment persistence in real-life conditions over a 3-year period. We have also investigated its effectiveness according to risk status at baseline and how patients’ risk status evolved over this period. The protocol was approved by the institutional review boards of all the participating hospitals, and patients provided written informed consent before being enrolled in the registry.