Selexipag-based initial triple therapy in Chinese PAH patients increased those achieving 3 low-risk criteria to 69.2% vs 33.3% with sequential therapy (p=0.000).
Does selexipag-based triple therapy improve risk stratification in Chinese patients with pulmonary arterial hypertension?
Selexipag-based triple therapy safely and effectively improves risk stratification and right heart function in Chinese patients with PAH, with initial triple therapy potentially offering superior benefits over sequential add-on.
Abstract Objective Selexipag, an oral prostacyclin receptor agonist, has been shown to be safe and effective for the treatment of pulmonary arterial hypertension (PAH). This study aims to elucidate the effectiveness and safety of selexipag-based triple therapy in Chinese patients with PAH. Methods This was a single-center, retrospective study, including 228 consecutive patients with PAH from February 2022 to November 2023 with a definitive diagnosis of Group 1 PAH by right heart catheterization, and who received a selexipag -based triple targeted therapy. The primary endpoint was improvement in the number of low-risk indices on the French Pulmonary Hypertension Registry (FPHR) noninvasive assessment 3-6 months following selexipag initiation. Low-risk indices were cardiac functional class (WHO) Ⅰ/Ⅱ, six-minute walking distance（6MWD） 440 m, and NT-proBNP 300 pg/ml. Comparison between initial and sequential triple combination were conducted after excluding patients with small atrial defect (ASD 2 cm). Results A total of 153 patients were entered into the safety cohort, and with another 7 excluded (selexipag treatment duration 3 months), 146 patients were included in the effectiveness cohort. In the effectiveness cohort, 120 (82.2%) were female, with a mean age of 31.9 years and a median time from PAH diagnosis to selexipag initiation of 36 months. Ninety (61.6%) patients presented with IPAH/HPAH of which 5 patients also had a small ASD, 29 (19.9%) patients with CHD-PAH after defect repair, and 27 (18.5%) patients with CTD-PAH. Twenty-seven patients received initial triple therapy, 106 patients had a sequential triple therapy, and 13 patients transitioned from triple combination with treprostinil to selexipag. The number of patients that had 3, 2, 1 or 0 low-risk criteria at baseline were 18 (12.3%), 26 (17.8%), 32 (21.9%), and 70 patients (47.9%), respectively. The risk stratification of patients improved significantly during follow-up, with the number of patients meeting 3 low-risk criteria increasing to 74 (50.7%), while there were still 22 (15.1%) patients who did not meet any low-risk criteria (Figure 1). Compared to sequential selexipag add on, initial triple therapy had more patients achieved 3 low-risk criteria (69.2% vs 33.3%, p = 0.000) at first follow-up and significant changes in right atrial area (-5 (-11, 0) vs -1 (-4, 2) cm2, p = 0.013), right ventricle diameter (-8 (-12, -3) vs -3 (-6, 1) mm, p = 0.001), and tricuspid annular plane systolic excursion (3 (1, 6) vs 1 (-1, 3) mm, p = 0.002) (Table 1). Not any unknown side effects were reported. Conclusions Triple-targeted drug therapy containing selexipag can be safely and effectively used in Chinese PAH patients, significantly enhancing exercise capacity, improving right heart function and optimizing risk stratification. Selexipag-based initial triple therapy may potentially offer superior benefits in improving risk stratification compared to sequential add-on therapy for PAH patients.Figure 1 Figure 2
Cui et al. (2025) studied this question. Selexipag-based initial triple therapy in Chinese PAH patients increased those achieving 3 low-risk criteria to 69.2% vs 33.3% with sequential therapy (p=0.000).