PO:32:178 | Effectiveness of oral anticoagulants in precapillary pulmonary hypertension associated with systemic sclerosis: a EUSTAR cohort study

Nicola Farina¹, Silvia Bellando-Randone¹, Hilde Jenssen-Bjørkekjær², David Launay³, Patricia Carreira⁴, Paolo Airò⁵, Serena Guiducci¹, Dilia Giuggioli⁶, Gabriela Riemekasten⁷, Carmen-Pilar Simeón Aznar⁸, Christina Bergmann⁹, Elise Siegart¹⁰, Ivan Castellví¹¹, Lesley Ann Saketkoo¹², Jeska De Vries-Bouwstra¹³, Philipp Klemm¹⁴, Ulf Müller-Ladner¹⁴, Alexandra Balbir-Gurman¹⁵, Vanessa Smith¹⁶, Florenzo Iannone¹⁷, Luca Idolazzi¹⁸, Christopher Denton¹⁹, Edoardo Rosato²⁰, Britta Maurer¹, Yannick Allanore¹, Yoshiya Tanaka¹, Elisabetta Zanatta¹, Oliver Distler¹, Marco Matucci-Cerinic¹, Cosimo Bruni¹ | ¹Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, Az Firenze, Italy; ²Department of Rheumatology, Hospital of Southern Norway Kristiansand, Norway; ³National Reference Center for Pulmonary Arterial Hypertension Pulmotension Lille, France; ⁴Hospital Universitario 12 de Octubre, Rheumatology Department Madrid Spain; ⁵ASST Spedali Civili of Brescia, University of Brescia, Rheumatology and Clinical Immunology Unit Brescia, Italy; ⁶Scleroderma Unit, Rheumatology Unit, University Hospital of Modena and Reggio Emilia Modena, Italy; ⁷Universitätsklinikum Schleswig-Holstein, Klinik für Rheumatologie und klinische Immunologie Lübeck Germany; ⁸Hospital Universitario Vall d'Hebron, Department of Internal Medicine, Systemic Autoimmune Diseases Unit Barcelona Spain; ⁹University Hospital Erlangen, Department Internal Medicine 3 Erlangen Germany; ¹⁰Charité University Hospital, Department of Rheumatology Berlin Germany; ¹¹Hospital de la Santa Creu i Sant Pau Baercelona Spain; ¹²New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center New Orleans, USA; ¹³Leiden University Medical Center, Department of Rheumatology Leiden, The Netherlands; ¹⁴JLU Giessen, Campus Kerckhoff, Department of Rheumatology and Clinical Immunology Center Bad Nauheim Germany; ¹⁵Rambam Health Care Campus, Rheumatology Institute Haifa, Israel; ¹⁶University of Ghent, Department of Rheumatology Ghent, Belgium; ¹⁷Rheumatology DiMePReJ, University of Bari, School of Medicine Bari, Italy; ¹⁸University of Verona, Section of Rheumatology, Department of Medicine Verona, Italy; ¹⁹Royal Free London and University College London Medical School, Centre for Rheumatology London, United Kingdom; ²⁰Sapienza University of Rome, Department of Translational and Precision Medicine Azienda Ospedaliero-Universitaria Policl Roma, Italy

Background. Precapillary pulmonary hypertension (pPH) in systemic sclerosis (SSc) associates with morbidity and mortality. The prothrombotic state observed in idiopathic pulmonary arterial hypertension has historically supported the use of oral anticoagulants (OAC) in its management. However, the benefit of OAC in SSc-related pPH 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 pPH.

Methods. We conducted a cohort study using the EUSTAR database to investigate the impact of OAC exposure vs. non-exposure on the prognosis of SSc patients with pPH 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 PH medication, starting 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 patients treated with OAC and untreated. 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.

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 prognostic outcomes.

Conclusions. 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. Prospective studies are needed to identify whether specific subgroups may benefit from OAC therapy.