OC.10 Association between vasoactive-vasodilating therapy and reduced detection of pulmonary arterial hypertension in systemic sclerosis: evidence from a EUSTAR study
Abstract
Introduction Vasoactive-vasodilating drugs (VVD) are the therapeutic cornerstone of pulmonary arterial hypertension (PAH), a form of precapillary pulmonary hypertension (pPH) that may complicate systemic sclerosis (SSc). VVD include endothelin receptor antagonists (ERAs), phosphodiesterase type 5 inhibitors (PDE5i), and prostanoids. As some VVDs are commonly used in SSc to treat digital ulcers (DU) and Raynaud’s phenomenon, we investigated the effectiveness of VVD on the primary prevention of SSc-pPH and, specifically, of PAH. Material and Methods SSc patients from the EUSTAR cohort who underwent right heart catheterization (RHC) were included; postcapillary PH cases were excluded. Multivariable logistic regression assessed the association between exposure to VVD (ongoing or ever; categories or specific molecules) and detection of pPH (mPAP>20 mmHg, PVR>2 WU and PWP<=15 mmHg) and of PAH (pPH, ILD extent <20% and FVC >70%). All models were adjusted for DLCO, age, current DU, sPAP on echocardiography, and interaction between VVDs and current DU. Results Among 944 eligible patients, 498 (53%) were diagnosed with pPH, of whom 367 (74%) had PAH. Patients with pPH were older, had more frequently anti-centromere antibodies, limited SSc, and had more frequently received ERAs and PDE5i. When testing VVD as categories in regression analysis, ERAs exposure was associated with a higher probability of pPH diagnosis. However, a significant interaction was found between these VVD and current digital ulcers (DU), which translated in a non-significant protective effect of ERAs exposure towards pPH detection in patients with current DU (ERAs ongoing: OR 0.435, 95%CI 0.193-1.064; ERAs ever: OR 0.636, 95%CI 0.349-1.158). No preventive effect was shown for ERAs in patients without current DU, as well as for PDE5i or prostanoids overall. When focusing on specific VVD molecules, a significant protective association with precapillary PH diagnosis was found for exposure ever to bosentan (OR 0.575, 95%CI 0.344-0.960), independently from current DU. Ongoing bosentan was associated with protective effects towards the diagnosis of pPH only in patients with current DU (OR 0.230, 95% CI 0.081 – 0.652), but not in those without DU. The protective effects of bosentan were confirmed in all sensitivity analyses targeting PAH detection. Conclusions Our data show that bosentan is associated with less frequent diagnosis of PAH and precapillary PH, in particular when employed in patients with current DU at the time of RHC. Our results support further research to optimize timing and patient selection for VVD therapy in SSc, aiming also at additional preventive effects at pulmonary level.
Authors 26
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IRCCS Ospedale San Raffaele · University of Florence
Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
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Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
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Inserm · Université de Lille · Centre Hospitalier Universitaire de Lille
Affiliation as printed
National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France
Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France
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Affiliation as printed
Department of Rheumatology, Hospital of Southern Norway, Kristiansand, Norway
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Affiliation as printed
Department of Statistics, Informatics and Applications, University of Florence, Florence, Italy
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Centre Hospitalier Universitaire de Bordeaux
Affiliation as printed
Rheumatology department, CHU de Bordeaux, Bordeaux, France
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Affiliation as printed
University of Ghent, Department of Rheumatology, Ghent, Belgium
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Carol Davila University of Medicine and Pharmacy
Affiliation as printed
Department of Rheumatology, St. Maria Hospital, Carol Davila, University of Medicine and Pharmacy, Bucarest, Romania
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Affiliation as printed
Department Internal Medicine 3, University Hospital Erlangen, Erlangen, Germany
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Université Paris Cité · Hôpital Cochin
Affiliation as printed
Rheumatology Department, Université Paris Cité, Cochin Hospital, Paris, France
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Justus-Liebig-Universität Gießen · Kerckhoff Klinik
Affiliation as printed
Department of Rheumatology and Clinical Immunology Center, JLU Giessen, Campus Kerckhoff, Bad Nauheim, Germany
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Affiliation as printed
Reumatologia, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy
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Affiliation as printed
Section of Rheumatology, Department of Medicine, University of Verona, Verona, Italy
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The Royal Free Hospital · University College London
Affiliation as printed
Centre for Rheumatology, Royal Free London and University College London Medical School, London, UK
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Azienda Ospedaliero Universitaria Policlinico "G.Rodolico - San Marco"
Affiliation as printed
Division of Rheumatology, A.O.U. Policlinico-San Marco, Catania, Italy
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Affiliation as printed
Department of Rheumatology, Clinical Immunology, Geriatrics and Internal Medicine, Medical University of Gdansk, Univers, Gdansk, Poland
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Hôpitaux Universitaires de Strasbourg
Affiliation as printed
Department of Rheumatology, University Hospital Strasbourg, Strasburg, France
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
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Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
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Inserm · Université de Lille · Centre Hospitalier Universitaire de Lille
Affiliation as printed
National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France
Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France
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Inserm · Université de Lille · Centre Hospitalier Universitaire de Lille
Affiliation as printed
National Reference Center for Pulmonary Arterial Hypertension (Pulmotension), Lille, France
Univ. Lille, Inserm, CHU Lille, Department of Internal Medicine and Clinical Immunology, Reference Center for Rare Autoi, Lille, France
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Leiden University Medical Center
Affiliation as printed
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
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Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
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Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
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Affiliation as printed
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Hospital, Milan, Italy
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Affiliation as printed
Department of Experimental and Clinical Medicine, Scleroderma Unit, Division of Rheumatology, University of Florence, AZ, Florence, Italy
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