Clinical outcomes with initial oral triple and dual therapy in echocardiography-defined connective tissue disease-associated pulmonary hypertension: a retrospective single-center cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Connective tissue disease-associated pulmonary hypertension (CTD-PH) is a serious complication, but evidence on early oral treatment intensification in patients followed primarily by echocardiography is limited. We evaluated outcomes associated with initial selexipag-containing oral triple therapy vs. dual therapy in echocardiography-defined CTD-PH. Methods: This single-center retrospective cohort included consecutive adults who initiated PH-targeted therapy between April 2020 and June 2025. Treatment was selected by treating physicians in routine care and was not randomized: dual therapy comprised macitentan plus tadalafil, whereas triple therapy additionally included selexipag. Baseline clinical, laboratory, and echocardiographic variables were obtained from standardized institutional assessments and reassessed at week 26. The primary endpoint was the change in the number (0–3) of European Society of Cardiology/European Respiratory Society (ESC/ERS) noninvasive low-risk criteria met: World Health Organization functional class (WHO-FC) I–II, 6-minute walk distance (6MWD) >440 m, and B-type natriuretic peptide (BNP) <50 ng/L or N-terminal pro-B-type natriuretic peptide (NT-proBNP) <300 ng/L. Complete cases with all three components available at both time points were analyzed without imputation. Disease-progression events were recorded through 30 weeks, and adverse events were assessed during follow-up. Results: Of 119 patients, 59 received triple therapy and 60 received dual therapy. The groups had similar baseline functional and biomarker profiles (6MWD, 290.0 vs. 286.9 m; NT-proBNP, 1,455 vs. 1,473 pg/mL); mean age was 45.5 vs. 47.2 years in the triple and dual therapy group respectively, and 93% vs. 83% were women. At week 26, the change in low-risk criteria differed between groups (P=0.003), with 57.6% vs. 33.3% meeting all the three criteria. Mean 6MWD increased by 156 vs. 104 m (adjusted difference, 52 m; 95% confidence interval (CI): 29–78; P<0.001), and WHO-FC distributions differed at week 26 (P=0.007). Exploratory analysis yielded an hazard ratio (HR) of 0.75 (95% CI: 0.39–1.43) for the first disease-progression event. At least one adverse event occurred in 53/59 (89.8%) vs. 47/60 (78.3%) patients; diarrhea occurred in 24/59 (40.7%) vs. 19/60 (31.7%), nausea in 21/59 (35.6%) vs. 16/60 (26.7%), and jaw pain in 16/59 (27.1%) vs. 11/60 (18.3%), with no significant between-group differences. Conclusions: In this real-world cohort of patients with echocardiography-defined CTD-PH, initial selexipag-containing oral triple therapy was associated with greater improvement in noninvasive ESC/ERS risk status and functional outcomes than dual therapy over 26 weeks, supporting further evaluation of noninvasive risk-guided oral treatment intensification in CTD-associated pulmonary vascular disease. However, given the small, single-center, nonrandomized retrospective design, these findings cannot establish superior efficacy or safety and require prospective multicenter confirmation with systematic hemodynamic assessment.
Source: Journal of Thoracic Disease
Institution: First Affiliated Hospital of Soochow University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7224112201