Initial treatment strategies and outcomes across haemodynamic thresholds and risk stratification in incident systemic sclerosis–associated pulmonary arterial hypertension: a EUSTAR analysis
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.
// Source
Authors: H. J. Bjørkekjær, Cosimo Bruni, Kaspar Broch, Cathrine Brunborg, Patricia Esmeralda Carreira, Paolo Airò, Carmen Pilar Simeón‐Aznar, Marie‐Elise Truchetet, Alessandro Giollo, Alexandra Balbir‐Gurman, Mickaël Martin, Christopher P. Denton, Armando Gabrielli, Francesco Del Galdo, Madelon C Vonk, Håvard Fretheim, Helle Bitter, Øyvind Midtvedt, Arne K. Andreassen, Sverre Høie, Yoshiya Tanaka, Gabriela Riemekasten, Ulf Müller‐Ladner, Marco Matucci‐Cerinic, Ivan Castellvi, Elise Siegert, Eric HACHULLA, Øyvind Molberg, Anastasiia Kozlova, Anna‐Maria Hoffmann‐Vold, the EUSTAR collaborators
Institutions: University of Padua, University of Verona, Charité - Universitätsmedizin Berlin, Düsseldorf University Hospital, Heinrich Heine University Düsseldorf, University College London, Hebron University, Inserm, Radboud University Nijmegen, Justus-Liebig-Universität Gießen, Université de Bordeaux, University of Zurich, University Hospital Zurich, University of Oslo, University of Florence, Hospital de Sant Pau, Research Institute Hospital 12 de Octubre, University of Lübeck, Vall d'Hebron Hospital Universitari, Marche Polytechnic University, Vita-Salute San Raffaele University, Université de Lille, Centre Hospitalier Universitaire de Lille, Rambam Health Care Campus, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, The Royal Free Hospital, Oslo University Hospital, Rappaport Family Institute for Research in the Medical Sciences, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Leeds Teaching Hospitals NHS Trust, Bordeaux Population Health, NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Occupational and Environmental Health Japan, IRCCS Ospedale San Raffaele, Kerckhoff Klinik, Hospital of Southern Norway, Centre Hospitalier Universitaire de Poitiers, Lille Inflammation Research International Center, Institutt for Eksperimentell Medisinsk Forskning