Selexipag-based triple combination therapy improves prognosis in Chinese pulmonary arterial hypertension patients

Abstract

AimSelexipag is an oral selective prostacyclin receptor agonist approved for treatment of patients with pulmonary arterial hypertension (PAH). In the present study, we aim to assess the safety and efficacy of selexipag in triple combination therapy with endothelial receptor antagonists (ERAs) and PDE5is for Chinese PAH patients.Methods and resultsA single center retrospective study was performed on group 1 PAH patients (n = 68) initiating triple combination therapy with selexipag from 1 February 2020 to 31 August 2021 in Qilu Hospital of Shandong University (Shandong, China). Adolescents, children, and PAH patients with unrepaired congenital heart disease were excluded. The French pulmonary hypertension network (FPHN) non-invasive risk assessment, echocardiogram parameters, and clinical data, including tolerability, safety, and death/hospitalization events associated with PAH, were collected. Of the 68 patients, 31 (45.6%) patients had tolerable side effects while only a single patient discontinued selexipag due to severe diarrhea. In the analysis of the efficacy set of 62 patients, the median selexipag treatment time from selexipag initiation to last risk assessment was 27 (21, 33) weeks. Compared to baseline parameters, the percentage of WHO FC III/IV decreased from 77.4% (48) to 24.2% (15) (p = 0.000), median 6-min walk distance (6MWD) increased 82 m [from 398 (318, 450) to 480 (420, 506) m; p = 0.000], and NT-proBNP levels decreased from 1,216 (329, 2,159) to 455 (134, 1,678) pg/mL (p = 0.007). Patients who improved to three low-risk criteria increased from 9.7 to 38.7%. Right ventricular diameter (RV) diameter also decreased and was accompanied by an improved tricuspid annular plane systolic excursion (TAPSE). Patients transitioning from subcutaneous treprostinil to selexipag continued to show improvements in WHO FC, 6MWD (404 ± 94 vs. 383 ± 127 m) and NT-proBNP levels (2,319 ± 2,448 vs. 2,987 ± 3,770 pg/mL). Finally, the 1-year event free survival rate was 96.7% for patients initiating the triple combination therapy within 3 years of PAH diagnosis.ConclusionTriple combination therapy with selexipag was safe and effective in Chinese PAH patients, which was confirmed by acceptable tolerability, and improved exercise capacity, right heart function, risk assessment, and prognosis.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension

“…These findings align with the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension 9 . However, Cui et al reported a higher 1‐year event‐free survival rate of 96.7% in PAH patients who received selexipag‐based initial triple combination therapy 17 . The difference in our data may be due to variations in gender ratios, risk stratification, and the type of initial triple or sequential triple combination therapy.…”

“… 9 However, Cui et al reported a higher 1‐year event‐free survival rate of 96.7% in PAH patients who received selexipag‐based initial triple combination therapy. 17 The difference in our data may be due to variations in gender ratios, risk stratification, and the type of initial triple or sequential triple combination therapy. Nevertheless, previous studies and our own indicated that selexipag‐based initial triple combination therapy has a positive impact on the prognosis of PAH patients.…”

“…The difference in our data may be due to variations in gender ratios, risk stratification, and the type of initial triple or sequential triple combination therapy. Nevertheless, previous studies and our own indicated that selexipag‐based initial triple combination therapy has a positive impact on the prognosis of PAH patients 14,16,17 …”

“…Nevertheless, previous studies and our own indicated that selexipag-based initial triple combination therapy has a positive impact on the prognosis of PAH patients. 14,16,17 Our study had several limitations. First, this was a retrospective multicenter study with a relatively small selected patients' group rather than a prospective multicenter study.…”

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study

“… 2 However, most such studies analyzed patients who were treated with oral drugs and parenteral administration of prostanoids, 5 , 6 , 7 while others had small sample sizes and were single‐center studies. 8 , 9 Therefore, evidence regarding the efficacy and safety of oral triple combination therapy remains scarce.…”