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SAT0434 Does Angiotensin and Endothelin Receptor Blockade Have an Impact on Lung Function? an Analysis from the Eustar Data Base
  1. M. Radić1,
  2. M.O. Becker2,
  3. O. Distler3,
  4. D. Huscher4,
  5. G. Riemekasten5
  1. 1Division of Rheumatology and Clinical Immunology, University Hospital Centre Split, University of Split School of Medicine, Split, Croatia, Split, Croatia
  2. 2Department of Rheumatology and Clinical Immunology, University Hospital Charité, Berlin, Germany
  3. 3Division of Rheumatology, University Hospital Zurich, Zürich, Switzerland
  4. 4Epidemiology Unit, German Rheumatism Research Centre Berlin, A Leibniz Institute
  5. 5Division of Rheumatology and Clinical Immunology, University Hospital Charité, Berlin, Germany

Abstract

Background Antibodies against the angiotensin II type-1 receptor and endothelin-1 type A receptor are simultaneously present in the majority of patients with systemic sclerosis (SSc) and high levels are associated with pulmonary arterial hypertension (PAH) and lung fibrosis. It is suggested that these antibodies may contribute to lung involvement by stimulating their receptors. Thus, angiotensin receptor blockers (ATRB) and/or endothelin receptor blockers (ETRB) may exhibit beneficial effects on lung function.

Objectives The objective of this study is to evaluate the possible benefit of simultaneous treatment with ETRB and ATRB.

Methods SSc patients with lung fibrosis prospectively followed in the EUSTAR database and treated with ETRB and/or ATRB were analyzed with regard to the evolution of forced vital capacities (FVC) and carbon monoxide diffusing capacities (DLCO) and were compared to patients without receptor blockade. Pulmonary fibrosis was defined by evidence of fibrosis such as bibasilar fibrosis on chest radiograms or HR-CT scans or both. Patients receiving immunosuppressive therapies were excluded. To adjust for confounders, patients receiving ATRB, ETRB, or both were matched for sex, SSc subtype, disease duration, and initial FVC/DLCO values.

Results 9,862 patients of the EUSTAR data base were analysed, of those, 764 patients took ETRB and 674 received ATRB. 410 of ETRB/ATRB patients had at least one annual follow-up (mean period of 13.12, SD 3.25 months). 239 patients from ETRB/ATRB group also received immunosuppressive therapies during this follow-up and were, therefore, excluded from further analyses. Finally, 31 patients with simultaneous ATRB/ETRB, 31 patients with ATRB, 31 patients with ETRB, and 31 patients not receiving any blockade were matched and compared. All patients treated with blockers fulfilled the ACR criteria. As expected, patients receiving ETRB had a higher prevalence of PAH (as suggested by echocardiography) and digital ulcers (DU), compared to those patients without blocker therapies. In contrast, the prevalence of these complications in patients receiving ATRB did not differ from the group without any blockade. Patients without any blockade unexpectedly did not show any reduction in DLCO levels during the follow up period. This reduction was prevented in patients receiving ATRB, as well as ATRB/ETRB in whom mostly stability of DLCO values was observed compared to baseline levels. There was no statistically significant improvement of predicted DLCO values by ≥10% according to treatment. There was no significant effect of ATRB or ETRB on FVC levels, although a higher proportion of patients (27.6%) showed improved FVC levels ≥10% when receiving ATRB, compared to 17.2% in the control group without blockers.

Conclusions The data do not indicate a potentially beneficial effect of ATRB or ETRB on lung function parameters, especially on DLCO values. Our study is limited by its size, observational design and different disease activity and severity between groups. Further studies are warranted to elucidate the role of angiotensin and endothelin receptor blockade in possible prevention of lung function deterioration.

Disclosure of Interest None declared

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