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 [ [1] Sitbon O. Vonk Noordegraaf A Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017; 26160055https://doi.org/10.1183/16000617.0055-2016 Crossref Scopus (50) Google Scholar ]. However, its complex route of administration (continuous intravenous infusion) and potentially serious administration-related side effects have limited its use in clinical practice [ [1] Sitbon O. Vonk Noordegraaf A Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017; 26160055https://doi.org/10.1183/16000617.0055-2016 Crossref Scopus (50) Google Scholar , [2] Lang I.M. Gaine S.P. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015; 24: 630-641https://doi.org/10.1183/16000617.0067-2015 Crossref PubMed Scopus (64) Google Scholar ]. 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 [ [2] Lang I.M. Gaine S.P. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015; 24: 630-641https://doi.org/10.1183/16000617.0067-2015 Crossref PubMed Scopus (64) Google Scholar ]. Given the relevance of targeting the prostacyclin pathway for PAH management, developing ways of enabling more convenient administration has been considered an urgent need [ [2] Lang I.M. Gaine S.P. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015; 24: 630-641https://doi.org/10.1183/16000617.0067-2015 Crossref PubMed Scopus (64) Google Scholar ]. 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 [ [3] Sitbon O. Channick R. Chin K.M. Frey A. Gaine S. Galie N. et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015; 373: 2522-2533https://doi.org/10.1056/NEJMoa1503184 Crossref PubMed Scopus (608) Google Scholar ]. 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 [ [4] Humbert M. Kovacs G. Hoeper M.M. Badagliacca R. Berger R.M.F. Brida M. et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022; 43: 3618-3731https://doi.org/10.1093/eurheartj/ehac237 Crossref PubMed Scopus (237) Google Scholar ]. 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 [ [5] Escribano-Subias P. Blanco I. Lopez-Meseguer M. Lopez-Guarch C.J. Roman A. Morales P. et al. Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J. 2012; 40: 596-603https://doi.org/10.1183/09031936.00101211 Crossref PubMed Scopus (287) Google Scholar ]. 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.