Background: In the EDITA trial, patients with systemic sclerosis (SSc) and mild pulmonary arterial hypertension (PAH) treated with ambrisentan had a significant decline of pulmonary vascular resistance (PVR) but not of mean pulmonary arterial pressure (mPAP) vs. placebo after 6 months [1].

Objectives: In the current study, we aimed to assess the long-term effects of continued therapy with ambrisentan vs. no vasodilative treatment (control).

Methods: Patients who participated in the EDITA study and received regular follow-up clinical assessments in our centre were included in this study. Clinical, echocardiographic, laboratory, exercise and hemodynamic parameters after the termination of study participation were analysed. The primary endpoint was to assess whether continued treatment with ambrisentan vs. control prevented the development of PAH according to the new definition [2].

Results: From 38 SSc-patients participating in the EDITA study 4 were lost to follow-up. Of the 34 remaining patients (age 55 ± years, 82.1% females), 19 received ambrisentan after the termination of the blinded phase and 15 continued with control. The mean follow-up time was 2.25±1.49 years, during which 29 patients underwent right heart catheterization. There was a significant improvement of mPAP in the group receiving ambrisentan vs. control (-1.53±2.53 vs 1.91±2.98 mmHg, p=0.003). In the control group four patients newly developed PAH with mPAP > 20 mmHg in contrast to none of the patients receiving ambrisentan (p=0.005, Figure 1).

Conclusion: Under continued targeted PAH therapy significantly more SSc patients were protected from deterioration of hemodynamics compared to patients receiving standard of care. Thus, early treatment and close follow-up could be beneficial in this risk group for impeding PH/PAH development. Future trials in this field are needed to confirm these results.

REFERENCES: [1] Pan Z, Marra AM, Benjamin N et al. Early treatment with ambrisentan of mildly elevated mean pulmonary arterial pressure associated with systemic sclerosis: a randomized, controlled, double-blind, parallel group study (EDITA study). Arthritis Res Ther. 2019 Oct 26;21(1):217.

[2] Humbert M, Kovacs G, Hoeper MM et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731.

Acknowledgements: We would like to thank all patients who participated in the study. This work was part of the doctoral thesis of PU.

Disclosure of Interests: Panagiota Xanthouli: None declared, Paul Uesbeck: None declared, Nicola Benjamin: None declared, Hanns-Martin Lorenz Abbvie, Astra-Zeneca, Actelion, Alexion, Amgen, Bayer Vital, Baxter, Biogen, Boehringer Ingelheim, BMS, Celgene, Fresenius, Genzyme, GSK, Gilead/Galapagos, Hexal, Janssen-Cilag, Lilly, Medac, MSD, Mundipharm, Mylan, Novartis, octapharm, Pfizer, Roche/Chugai, Sandoz, Sanofi, Shire, SOBI, Thermo Fisher, UCB, Christina Alessandra Eichstaedt: None declared, Satenik Harutyunova: None declared, Benjamin Egenlauf: None declared, Ekkehard Grünig Actelion, Bayer AG, MSD, SCOPE, OrPha Swiss GmbH, Zurich Heart House, GSK, Novartis, and United Therapeutics.