Initial treatment strategies and outcomes across haemodynamic thresholds and risk stratification in incident systemic sclerosis–associated pulmonary arterial hypertension: a EUSTAR analysis

OBJECTIVE: Real-world initial treatment strategies in SSc-PAH remain incompletely described. We aimed to characterise these strategies across haemodynamic thresholds and risk strata and evaluate outcome associations. METHODS: We analysed treatment-naïve SSc-PAH patients in EUSTAR (2000-2021) fulfilling the 2022 haemodynamic definition. Initial therapy comprised treatment initiated within 4 months of RHC. As-treated (AT) analyses were primary and intention-to-treat (ITT) analyses supportive. Outcomes were all-cause mortality and 36-month PAH progression. RESULTS: Among 301 patients, 198 (66%) initiated therapy and 170 maintained therapy for ≥3 months. Therapy was initiated in 31% with milder haemodynamic impairment (mPAP 21-24 mmHg and/or PVR 2-3 WU) versus 79% fulfilling the previous haemodynamic definition; combination therapy increased from 14% to 67% across low- to high-risk strata. Over a median 3.9 years, 125 (42%) died and 85/227 (37%) progressed. Adjusted ITT analyses showed no association with either outcome, whereas adjusted AT analyses showed lower mortality risk with sustained monotherapy and combination therapy (HR 0.50, 95% CI 0.27-0.92 and HR 0.40, 95% CI 0.18-0.88, respectively) and lower PAH progression risk with sustained initial therapy (HR 0.37, 95% CI 0.18-0.76). In the milder haemodynamic subgroup, the mortality estimate was directionally consistent but imprecise. CONCLUSION: Initial treatment strategies reflected haemodynamic severity and baseline risk, while variation suggested potential implementation gaps. Sustained initial therapy was associated with lower risks of mortality and PAH progression. Contrasting ITT and AT estimates highlight challenges in observational treatment-outcome comparisons. Findings in the milder haemodynamic subgroup support dedicated prospective studies.

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Journal
Arthritis & Rheumatology
Published
2026-10-15
DOI
https://doi.org/10.1002/art.70372
Primary Topic
Pulmonary Hypertension Research and Treatments
Type
article
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article

Initial treatment strategies and outcomes across haemodynamic thresholds and risk stratification in incident systemic sclerosis–associated pulmonary arterial hypertension: a EUSTAR analysis

Anna‐Maria Hoffmann‐Vold, Helle Bitter, Ivan Castellvi, Øyvind Molberg et al.
Arthritis & Rheumatology
Pulmonary Hypertension Research and Treatments
article

Initial treatment strategies and outcomes across haemodynamic thresholds and risk stratification in incident systemic sclerosis–associated pulmonary arterial hypertension: a EUSTAR analysis

Anna‐Maria Hoffmann‐Vold, Helle Bitter, Ivan Castellvi, Øyvind Molberg, H. J. Bjørkekjær, Yoshiya Tanaka, Alexandra Balbir‐Gurman, Gabriela Riemekasten, Eric HACHULLA, Cathrine Brunborg, Sverre Høie, Kaspar Broch, Øyvind Midtvedt, Marco Matucci‐Cerinic, Marie‐Elise Truchetet, Alessandro Giollo, Madelon C Vonk, Arne K. Andreassen, Cosimo Bruni, Elise Siegert, Francesco Del Galdo, Patricia Esmeralda Carreira, Mickaël Martin, Paolo Airò, Carmen Pilar Simeón‐Aznar, Armando Gabrielli, Christopher Paul Denton, Ulf Müller‐Ladner, Anastasiia Kozlova, the EUSTAR collaborators, Håvard Fretheim
article en

Abstract

OBJECTIVE: Real-world initial treatment strategies in SSc-PAH remain incompletely described. We aimed to characterise these strategies across haemodynamic thresholds and risk strata and evaluate outcome associations. METHODS: We analysed treatment-naïve SSc-PAH patients in EUSTAR (2000-2021) fulfilling the 2022 haemodynamic definition. Initial therapy comprised treatment initiated within 4 months of RHC. As-treated (AT) analyses were primary and intention-to-treat (ITT) analyses supportive. Outcomes were all-cause mortality and 36-month PAH progression. RESULTS: Among 301 patients, 198 (66%) initiated therapy and 170 maintained therapy for ≥3 months. Therapy was initiated in 31% with milder haemodynamic impairment (mPAP 21-24 mmHg and/or PVR 2-3 WU) versus 79% fulfilling the previous haemodynamic definition; combination therapy increased from 14% to 67% across low- to high-risk strata. Over a median 3.9 years, 125 (42%) died and 85/227 (37%) progressed. Adjusted ITT analyses showed no association with either outcome, whereas adjusted AT analyses showed lower mortality risk with sustained monotherapy and combination therapy (HR 0.50, 95% CI 0.27-0.92 and HR 0.40, 95% CI 0.18-0.88, respectively) and lower PAH progression risk with sustained initial therapy (HR 0.37, 95% CI 0.18-0.76). In the milder haemodynamic subgroup, the mortality estimate was directionally consistent but imprecise. CONCLUSION: Initial treatment strategies reflected haemodynamic severity and baseline risk, while variation suggested potential implementation gaps. Sustained initial therapy was associated with lower risks of mortality and PAH progression. Contrasting ITT and AT estimates highlight challenges in observational treatment-outcome comparisons. Findings in the milder haemodynamic subgroup support dedicated prospective studies.

Arthritis & Rheumatology
University of Verona (IT), Marche Polytechnic University (IT), Hebron University (PS), Oslo University Hospital (NO), University of Padua (IT), Radboud University Nijmegen (NL), Université de Bordeaux (FR), Vita-Salute San Raffaele University (IT), Inserm (FR), University of Oslo (NO), University of Occupational and Environmental Health Japan (JP), Justus-Liebig-Universität Gießen (DE), University of Zurich (CH), Université de Lille (FR), Leeds Teaching Hospitals NHS Trust (GB), The Royal Free Hospital (GB), Rambam Health Care Campus (IL), Hospital de Sant Pau (ES), Hospital of Southern Norway (NO), Centre Hospitalier Universitaire de Lille (FR), Research Institute Hospital 12 de Octubre (ES), Düsseldorf University Hospital (DE), University Hospital of Zurich (CH), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Bordeaux Population Health (FR), Centre Hospitalier Universitaire de Poitiers (FR), NIHR Leeds Musculoskeletal Biomedical Research Unit (GB), Rappaport Family Institute for Research in the Medical Sciences (IL), Institutt for Eksperimentell Medisinsk Forskning (NO), Vall d'Hebron Hospital Universitari (ES), Lille Inflammation Research International Center (FR), IRCCS Ospedale San Raffaele (IT), Kerckhoff Klinik (DE), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), Heinrich Heine University Düsseldorf (DE), University of Florence (IT), University College London (GB), Charité - Universitätsmedizin Berlin (DE), University of Lübeck (DE)
Novartis Foundation, Wellcome Trust, Novartis Stiftung für Medizinisch-Biologische Forschung, EMDO Stiftung
Good health and well-being
Openalex Percentile: Top 13%
Pulmonary Hypertension Research and Treatments
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