Effectiveness of Oral Anticoagulants in Precapillary Pulmonary Hypertension Associated with Systemic Sclerosis: a EUSTAR Cohort Study.

Nicola Farina¹, Silvia Bellando-Randone², hilde Bjørkekjær³, David Launay⁴, Patricia E. Carreira⁵, paolo airò⁶, Serena Guiducci⁷, Dilia Giuggioli⁸, Gabriela Riemekasten⁹, carmen-Pilar Simeón Aznar¹⁰, Christina Bergmann¹¹, Elise Siegert¹², Ivan Castellví¹³, Lesley Ann Saketkoo¹⁴, Jeska de Vries-Bouwstra¹⁵, Dr. Philipp Klemm¹⁶, ulf Müller-Ladner¹⁷, Alexandra Balbir- Gurman¹⁸, Vanessa Smith¹⁹, Florenzo Iannone²⁰, Luca Idolazzi²¹, Christopher Denton²², edoardo rosato²³, Britta Maurer²⁴, Yannick Allanore²⁵, Yoshiya Tanaka²⁶, elisabetta zanatta²⁷, Marie-Elise Truchetet²⁸, Masataka Kuwana²⁹, Mickaël MARTIN³⁰, Alberto Cauli³¹, Kamal Solanki³², Francesco Del Galdo³³, Ana Maria Gheorghiu³⁴, Branimir Anic³⁵, Gábor Kumánovics³⁶, Gonçalo Boleto³⁷, Kristofer Andréasson³⁸, Simona Rednic³⁹, Lorinda Chung⁴⁰, susana Oliveira⁴¹, marius cadar⁴², Francesco Paolo Cantatore⁴³, Carolina de Souza Müller⁴⁴, Vivien Hsu⁴⁵, Yair Levy⁴⁶, Gianluca Moroncini⁴⁷, Jörg Henes⁴⁸, Andra Balanescu⁴⁹ and Ellen De Langhe⁵⁰, ¹Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence, Italy. Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy, Milan, Italy, ²University of Florence, Florence, Florence, Italy, ³Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway, olso, Norway, ⁴Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoimmune and Autoinflammatory diseases (CERAINOM), U¹²⁸⁶ - INFINITE - Institute for Translational Research in Inflammation, Lille, France. National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France, Lille Cedex, France, ⁵Hospital Universitario ¹² de Octubre, Madrid, Spain, ⁶Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia, University of Brescia, Brescia, Italy, brescia, Italy, ⁷Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence, Italy, Pistoia, Italy, ⁸Scleroderma Unit, Rheumatology Unit, University Hospital of Modena and Reggio Emilia, Modena, Italy, Modena, Italy, ⁹University Clinic Schleswit-Holstein (UKSH), Lübeck, Germany, ¹⁰Hospital Universitario Vall d'Hebron Passeig, Department of Internal Medicine, Systemic Autoimmune Diseases Unit, Barcelona, Spain, Zaragoza, Spain, ¹¹Department of Medicine ³ - Rheumatology and Immunology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany, ¹²Charité University Hospital, Department of Rheumatology, Berlin, Germany, Berlin, Germany, ¹³Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, barcelona, Spain, ¹⁴University Medical Center - Comprehensive Pulmonary Hypertension Center and ILD Clinic Programs // New Orleans Scleroderma and Sarcoidosis Patient Care & Research Centeris, New Orleans, LA, ¹⁵Leiden University Medical Center, Leiden, Netherlands, ¹⁶Kerckhoff-Klinik Bad Nauheim, Berlin, Germany, ¹⁷JLU Giessen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology Center, Bad Nauheim, Germany, Bad Nauheim, Germany, ¹⁸Rambam Health Care Campus, Rheumatology Institute, Haifa, Israel, israel, Israel, ¹⁹Ghent University Hospital, Gent, Belgium, ²⁰Rheumatology DiMePReJ, University of Bari, School of Medicine, Bari, Italy, Bari, Italy, ²¹Section of Rheumatology, Department of Medicine, University of Verona, Verona, Italy, verona, Italy, ²²University College London, UK, London, United Kingdom, ²³Sapienza University of Rome, Department of Translational and Precision Medicine Azienda Ospedaliero-Universitaria Policlinico Umberto ¹-Centro di riferimento regionale per la sclerosi sistemica, Rome, Italy, rome, Italy, ²⁴Department of Rheumatology & Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, ²⁵Université Paris Cité, Paris, France, ²⁶University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, ²⁷Padova University Hospital, Rheumatology Unit, Padova, Italy, padova, Italy, ²⁸Bordeaux University Hospital, Bordeaux, France, ²⁹Nippon Medical School Graduate School of Medicine, Tokyo, Japan, ³⁰Poitiers University Hospital, Department of Internal Medicine, Poitiers, France, MIGNALOUX-BEAUVOIR, France, ³¹Rheumatology Unit, Department of Medicine and Public Health, AOU and University of Cagliari, Cagliari, Italy, ³²Waikato Hospital, Hamilton, New Zealand, ³³University of Leeds, Leeds, United Kingdom, ³⁴Spitalul Clinic Dr. Ion Cantacuzino, Bucharest, Romania, ³⁵University of Zagreb, School of Medicine, University Hospital Center Zagreb, Division of Clinical Immunology and Rheumatology, Department of Internal Medicine, Zagreb, Croatia, zagreb, Croatia, ³⁶University of Pécs, Department Of Rheumatology And Immunology, Medical Centre, Pecs, Hungary, Pecs, Hungary, ³⁷Local de Saúde Santa Maria, Centro Académico de Medicina de Lisboa, Rheumatology Department, Lisbon, Portugal, Paris, France, ³⁸Skåne University Hospital, Department of Rheumatology, Lund, Sweden, Lund, Sweden, ³⁹University of Medicine and Pharmacy Iuliu Hatieganu Cluj, Clinica Reumatologie, Cluj-Napoca, Romania, Cluj-Napoca, Romania, ⁴⁰Stanford University, Stanford, CA, ⁴¹Fernando Fonseca Hospital, Department of Medicine IV, Systemic Immunomediated Diseases Unit, Amadora, Portugal, amadora, Portugal, ⁴²Sapienza University of Rome, Rheumatology Clinic, Rome, Italy, Rome, Italy, ⁴³University of Foggia, Department of Medical and Surgical Sciences, Rheumatology Unit, Foggia, Italy, foggia, Italy, ⁴⁴Hospital de Clinicas da Universidade Federal do Parana, Curitiba, Brazil, curitiba, Brazil, ⁴⁵Rutgers- RWJ Medical School, South Plainfield, NJ, ⁴⁶Meir Medical Center, Kfar-Saba, Israel, Kefar Sava, Israel, ⁴⁷Department of Internal Medicine, Marche University Hospital, Clinica Medica, Ancona, Italy, Ancona, Italy, ⁴⁸Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology, and Rheumatology, University Hospital Tübingen, Tuebingen, Germany, ⁴⁹UNIVERSITY OF MEDICINE AND PHARMACY CAROL DAVILA, Bucharest, Romania, ⁵⁰University Hospital Leuven, Laboratory of Tissue Homeostasis and Disease, Department of Development and Regeneration, KU Leuven, Leuven, Belgium, Leuven, Belgium

Meeting: ACR Convergence 2025

Keywords: pulmonary, Systemic sclerosis, Therapy, alternative

Session Information

Date: Sunday, October 26, 2025

Title: (0671–0710) Systemic Sclerosis & Related Disorders – Clinical Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Precapillary pulmonary hypertension (PH) in systemic sclerosis (SSc) associates with severe morbidity and mortality. The prothrombotic state observed in idiopathic pulmonary arterial hypertension (PAH) has historically supported the use of oral anticoagulants (OAC) in its management. However, the benefit of OAC in SSc-related precapillary PH remains uncertain, with studies reporting conflicting results, including possible harm. The objective of this study was to evaluate whether OAC use is associated with improved survival or reduced disease worsening in SSc patients with precapillary PH.

Methods: We conducted a cohort study using the European Scleroderma Trial and Research (EUSTAR) database to investigate the impact of OAC exposure vs. non-exposure on the prognosis of SSc patients with precapillary PH confirmed by right heart catheterization (RHC- mean PAP >20 mmHg, PVR >2 WU and PWP≤15 mmHg). Exposure to OAC was defined when lasting for at least 3 months after the RHC diagnosis.The primary outcome was a combination of all-cause death or otherwise PH worsening, the latter defined as at least one of the following: decrease of 6MWD >15%, worsening of NYHA class, onset of right heart failure, additional PAH medication, starting i.v./s.c. prostanoids, lung transplantation, or atrial septostomy. Mortality and PH worsening were also analyzed as secondary endpoints. Multivariable Cox regression was used to assess associations of exposure to OAC and the endpoints. Additionally, propensity score matching (PSM) was performed to balance confounding factors among OAC treated vs. untreated patients. Time to endpoints was assessed using Kaplan Mayer estimates. Covariates for both Cox regression and PSM were chosen based on literature support and included risk factors for worse prognosis in SSc and PH (i.e., age, sex, mPAP, reduced cardiac index, DLCO%). Missing data on the covariates were imputed using the Random Forest algorithm.

Results: Among 644 eligible patients, 173 (27%) received OAC at the time of RHC or afterwards. Patients treated with OAC were older and had more severe hemodynamic parameters (Table 1). During a median follow-up of 4 (2-6) years, 40% of patients died and 49% experienced PH worsening. Both events were recorded more frequently in the group treated with OAC, compared to non-treated patients (46% vs 37% and 59% vs 45%, respectively). Cox regression analysis did not show any significant association between OAC exposure and the combined endpoint (HR 0.996, 95% CI 0.794–1.249), mortality (HR 0.991, 95% CI 0.743–1.320) or PH worsening (HR 1.093, 95% CI 0.846–1.412) – Figure 1. PSM identified two balanced groups of 148 patients exposed and 148 not exposed to OAC. Kaplan Meier curves (Figure 2) confirmed the lack of association between OAC and the explored prognostic outcomes.

Conclusion: In this large multicenter cohort of SSc patients with precapillary PH, OAC therapy did not impact survival or disease worsening. These findings argue against the routine use of anticoagulation in this population and highlight the importance of individualized treatment decisions based on comorbidities and safety profile. Prospective studies are needed to identify whether specific subgroups may benefit from OAC therapy.

Table 1. Data about demographics, disease features, treatment exposure, functional and hemodynamic parameters, and outcome variables, compared between patients who received oral anticoagulants and those who did not. Categorial and continuous variables are reported as absolute numbers (%) and mean (standard deviation), respectively.

BNP, brain natriuretic peptide; CI, cardiac index; DLCO, diffusion lung capacity of carbon monoxide; HR, hazard ratio; HRCT, high resolution computed tomography; ILD; interstitial lung disease; mPAP, mean pulmonary arterial pressure; NYHA, New York Heart Association; PH, pulmonary hypertension; 6MWT, 6-minute walking test. Bold represents statistical significance with p value < 0.05.

Figure 1. Forest plots of multivariable regression models testing the association between exposure to oral anticoagulants and the prognosis (panel a primary endpoint, panel b death, panel c pulmonary hypertension worsening) of patients with pulmonary arterial hypertension at right heart catheterization.

Figure 2. Survival curves for different outcome variables according to the exposure status to oral anticoagulants, in the match-control population identified using propensity score matching.

NYHA:New York Heart Association; OAC, oral anticoagulants; PH, pulmonary hypertension.

Disclosures: N. Farina: None; S. Bellando-Randone: Boehringer-Ingelheim, 2, 6; h. Bjørkekjær: Janssen, 5; D. Launay: AstraZeneca, 2, 6, BioCryst, 6, 12, travel grants, CSL Behring, 2, 6, Shire, 12, travel grants, Takeda, 2, 6; P. Carreira: AstraZeneca, 2, 6, Boehringer-Ingelheim, 2, 6, Corbus, 2, 6, Emmerald Health Pharmaceuticals, 2, 6, Janssen, 2, 6, Mitsubishi Tanabe, 2, 6, Novartis, 2, 6, Prometheus, 2, 6; p. airò: Amgen, 12, meeting/travel support, CSL Behring, 12, meeting/travel support, Eli Lilly, 12, meeting/travel support, Janssen, 6, 12, meeting/travel support, Novartis, 6; S. Guiducci: None; D. Giuggioli: None; G. Riemekasten: AbbVie/Abbott, 6, Boehringer-Ingelheim, 2, 6, Galapagos, 6, Janssen, 2, 6, Merck/MSD, 6, Novartis, 6, Roche, 6, Sanofi, 5; c. Simeón Aznar: Boehringer-Ingelheim, 2, 6, 12, travel grants, Janssen, 2, 6, 12, travel grants, Merck/MSD, 6; C. Bergmann: None; E. Siegert: None; I. Castellví: Boehringer-Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 6, Gebro, 6, GlaxoSmithKlein(GSK), 2, Innovarderm, 2, Janssen, 2, 6, Kern Pharma, 2, 6, Novartis, 2, Roche, 6, Sanofi-Genzyme, 6; L. Saketkoo: Abbvie, 6, Argenx, 1, 2, 5, aTyr Pharmaceuticals, 12,, 1, 5, Boehringer-Ingelheim, 2, 5, 6, CSL Behring, 5, EMD Serono, 2, 5, Horizon, 5, Johnson & Johnson, 6, Kadmon, 5, Kinevant, 12,, 2, 5, Mallinckrodt, 1, 2, 5, Novartis, 1, 2, 5, Priovant, 5; J. de Vries-Bouwstra: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Jannsen-Cilag, 5, Janssen, 2, 6, Roche, 5; D. Klemm: None; u. Müller-Ladner: None; A. Balbir- Gurman: None; V. Smith: Argenx, 2, Boehringer-Ingelheim, 2, 5, 6, GlaxoSmithKlein(GSK), 2, Janssen, 2, 5, 6; F. Iannone: None; L. Idolazzi: None; C. Denton: AbbVie/Abbott, 2, Boehringer-Ingelheim, 2, Certa Pharmaeuticals, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Novartis, 2; e. rosato: None; B. Maurer: AbbVie/Abbott, 5, Actelion, 12, Congress support, Boehringer-Ingelheim, 1, 5, 6, GlaxoSmithKlein(GSK), 2, Janssen, 2, Medtalk, 12, Congress support, Mepha, 12, Congress support, Merck/MSD, 12, Congress support, Novartis, 2, 5, 6, Otsuka, 6, Pfizer, 12, Congress support, Protogen, 5, Roche, 12, Congress support, UCB, 12, Congress support; Y. Allanore: None; Y. Tanaka: AbbVie, 6, AstraZeneca, 6, BMS, 6, Boehringer Ingelheim, 6, Chugai, 6, Daiichi Sankyo, 6, Eisai, 6, Eli Lilly & Co., 6, Gilead, 6, GSK, 6, IQVIA, 6, Otsuka, 6, Taisho, 6, UCB, 6; e. zanatta: None; M. Truchetet: AbbVie/Abbott, 2, 12, travel grants, Boehringer-Ingelheim, 2, Eli Lilly, 2, 6, Galapagos, 6, Merck/MSD, 6, Novartis, 6, Pfizer, 2, UCB, 2; M. Kuwana: AbbVie, 2, Asahi Kasei Pharma, 6, AstraZeneca, 2, Boehringer-Ingelheim, 2, 5, 6, Chugai, 2, 6, GlaxoSmithKlein(GSK), 2, Medical and Biological Laboratories, 5, 9, Mochida, 2, Novartis, 2, Ono Pharmaceuticals, 6; M. MARTIN: None; A. Cauli: None; K. Solanki: Apollo Hospitals Educational and Research Foundations, 12, Honorary adjunct professor; F. Del Galdo: AbbVie/Abbott, 2, 5, argenx, 2, 5, AstraZeneca, 2, 5, Boehringer-Ingelheim, 2, 5, Calluna, 2, 5, Deepcure, 2, 5, Engitix, 2, 5, GlaxoSmithKlein(GSK), 2, 5, Janssen, 2, 5, Merck/MSD, 2, 5, Miltenyi, 2, 5, Mitsubishi-Tanabe, 2, 5, Novartis, 2, 5, Ono, 2, 5, Quell, 2, 5, RelationX, 2, 5, Serono, 2, 5, Syntara, 2, 5, Ventus, 2, 5, ZuraBio, 2, 5; A. Gheorghiu: Boehringer-Ingelheim, 6, Foundation for research in Rheumatology (FOREUM), 5; B. Anic: None; G. Kumánovics: None; G. Boleto: Boehringer-Ingelheim, 12, support for attending meetings; K. Andréasson: Janssen, 6; S. Rednic: None; L. Chung: AbbVie/Abbott, 1, Boehringer-Ingelheim, 1, CRISPR Therpeutics, 2, Cure Ventures, 2, jade, 2, Kyverna, 6, Mediar, 1, 2; s. Oliveira: None; m. cadar: None; F. Cantatore: None; C. de Souza Müller: None; V. Hsu: None; Y. Levy: None; G. Moroncini: None; J. Henes: AbbVie/Abbott, 1, 6, AstraZeneca, 1, 6, Boehringer-Ingelheim, 1, 6, Bristol-Myers Squibb(BMS), 1, 6, Eli Lilly, 1, Janssen, 1, 6, Novartis, 1, 1, 6, 6, Otsuka, 1, Pfizer, 1, Roche, 1, SOBI, 1, UCB, 1, 6; A. Balanescu: AbbVie/Abbott, 1, 6, Amgen, 2, 6, Angellini, 6, AstraZeneca, 6, Boehringer-Ingelheim, 6, Eli Lilly, 6, Ewopharma, 6, Janssen, 6, Novartis, 6, Pfizer, 6, Sandoz, 6, Sobi, 2, 6, Stada, 2, 6, Theramex, 6, UCB, 2, 6; E. De Langhe: None.

To cite this abstract in AMA style:

Farina N, Bellando-Randone S, Bjørkekjær h, Launay D, Carreira P, airò p, Guiducci S, Giuggioli D, Riemekasten G, Simeón Aznar c, Bergmann C, Siegert E, Castellví I, Saketkoo L, de Vries-Bouwstra J, Klemm D, Müller-Ladner u, Balbir- Gurman A, Smith V, Iannone F, Idolazzi L, Denton C, rosato e, Maurer B, Allanore Y, Tanaka Y, zanatta e, Truchetet M, Kuwana M, MARTIN M, Cauli A, Solanki K, Del Galdo F, Gheorghiu A, Anic B, Kumánovics G, Boleto G, Andréasson K, Rednic S, Chung L, Oliveira s, cadar m, Cantatore F, de Souza Müller C, Hsu V, Levy Y, Moroncini G, Henes J, Balanescu A, De Langhe E. Effectiveness of Oral Anticoagulants in Precapillary Pulmonary Hypertension Associated with Systemic Sclerosis: a EUSTAR Cohort Study. [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/effectiveness-of-oral-anticoagulants-in-precapillary-pulmonary-hypertension-associated-with-systemic-sclerosis-a-eustar-cohort-study/. Accessed .

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effectiveness-of-oral-anticoagulants-in-precapillary-pulmonary-hypertension-associated-with-systemic-sclerosis-a-eustar-cohort-study/