Real-world analysis on hemodynamic effectiveness and adverse events of selexipag in pulmonary arterial hypertension

Background Selexipag, an oral IP prostacyclin receptor agonist, improves outcomes in pulmonary arterial hypertension (PAH); however, real-world hemodynamic data and the relationship between adverse events (AEs) and treatment response are limited. Objectives The aims of this study were to evaluate the efficacy and safety of selexipag in a Japanese cohort and assess whether treatment-emergent adverse events, particularly headache and diarrhea, were associated with subsequent hemodynamic responses. Design We conducted a retrospective observational study at the National Cerebral and Cardiovascular Center in Japan. Methods We retrospectively analyzed consecutive patients with PAH initiating selexipag at our institution between 2016 and 2022. Baseline and follow-up right heart catheterization, 6-minute walk distance (6MWD), and B-type natriuretic peptide (BNP) were assessed at 26, 52, and 104 weeks. AEs requiring treatment were recorded. Results Of the 97 included patients, 94% received dual or triple PAH therapies at baseline. At 52 weeks, selexipag was associated with reductions in pulmonary vascular resistance (−1.36±4.70 Wood units; p =0.036) and mean pulmonary artery pressure (mPAP; −4.27±9.61 mmHg; p =0.001) and an increase in 6MWD (+26.6±53.8 m; p =0.003), without significant changes in cardiac index or BNP. The proportion of patients at low ESC/ERS 3-strata risk increased from 63% to 78% ( p =0.017). AEs occurred in 62% of patients, most commonly headache (42%) and diarrhea (29%). Headaches, typically developing during dose escalation, might be associated with a better prognosis through greater mPAP reduction. Conclusion Selexipag initiation improved pulmonary hemodynamics, exercise capacity, and risk profile, without new safety signals. Headache, a common prostacyclin-related AE, may indicate treatment responsiveness and predict therapeutic outcomes. Careful titration to the maximally tolerated dose with vigilant AE management may optimize outcomes.