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BackgroundSelexipag, 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.ObjectivesThe 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.DesignWe conducted a retrospective observational study at the National Cerebral and Cardiovascular Center in Japan.MethodsWe 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.ResultsOf 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.ConclusionSelexipag 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.