Clinical outcomes with initial oral triple and dual therapy in echocardiography-defined connective tissue disease-associated pulmonary hypertension: a retrospective single-center cohort study.
- 1Department of Rheumatology and Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Abstract
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. 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. 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. 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.
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BibTeX
@article{shen2026clinical,
title = {{Clinical outcomes with initial oral triple and dual therapy in echocardiography-defined connective tissue disease-associated pulmonary hypertension: a retrospective single-center cohort study.}},
author = {Xinyi Shen and Qingyi Chen and Menghuan Ren and Lei Wang and Jian Wu and Jing Cao and Yufeng Yin and Tian Ren and Xin Zhou and Tao Cheng and Mingjun Wang},
journal = {Journal of thoracic disease},
year = {2026},
month = oct,
doi = {10.21037/jtd-2026-2748},
url = {https://europepmc.org/article/MED/42996963},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Clinical outcomes with initial oral triple and dual therapy in echocardiography-defined connective tissue disease-associated pulmonary hypertension: a retrospective single-center cohort study.
AU - Xinyi Shen
AU - Qingyi Chen
AU - Menghuan Ren
AU - Lei Wang
AU - Jian Wu
AU - Jing Cao
AU - Yufeng Yin
AU - Tian Ren
AU - Xin Zhou
AU - Tao Cheng
AU - Mingjun Wang
PY - 2026
DA - 2026/10/26
JO - Journal of thoracic disease
DO - 10.21037/jtd-2026-2748
UR - https://europepmc.org/article/MED/42996963
AB - 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. 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. 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. 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.
SN - 2072-1439
SN - 2077-6624
ER -