B Koller1, R Steringer-Mascherbauer2, C H Ebner2, Th Weber3, M Ammer3, J Eichinger4, I Pretsch4, M Herold5, J Schwaiger1, H Ulmer6, W Grander7. 1. University Teaching Hospital Hall in Tyrol, Department for Internal Medicine, Hall in Tyrol, Austria. 2. Convent Hospital Elisabethinen, Linz, Internal Department II- Cardiology, Angiology, Internal Intensive Medicine, Linz, Austria. 3. Community Hospital Wels-Grieskirchen, Internal Department II - Cardiology and Intensive Care Medicine, Wels, Austria. 4. University Hospital Salzburg, Internal Department II - Cardiology and Intensive Care Medicine, Salzburg, Austria. 5. Medical University Innsbruck, Department for Internal Medicine VI, Innsbruck, Austria. 6. Medical University Innsbruck, Department for Medical Statistics, Informatics and Health Economics, Innsbruck, Austria. 7. University Teaching Hospital Hall in Tyrol, Department for Internal Medicine, Hall in Tyrol, Austria. Electronic address: wilhelm.grander@tirol-kliniken.at.
Abstract
BACKGROUND: In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). MATERIALS AND METHODS: Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. RESULTS:Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). CONCLUSION: Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.
RCT Entities:
BACKGROUND: In this multi-centre, randomised, placebo-controlled pilot trial, we investigated the clinical and haemodynamic effects of the endothelin-receptor blocker Bosentan in patients with heart failure, preserved ejection fraction and pulmonary hypertension (PH-HFpEF). MATERIALS AND METHODS: Eligible patients received either 12 weeks of Bosentan therapy, or a placebo drug. Patients were thereafter followed for a further period of 12 weeks without the study medication. At three points during the study (study Commencement, Week 12 and Week 24), a six-minute walk test (6MWT), echocardiographic and laboratory assessments were performed, as well as a quality of life survey. Right heart catheterisation (RHC) was undertaken at commencement only. The study was aborted early, after an interim analysis favoured the placebo. RESULTS: Six-minute walk distance (6MWD) did not change in the Bosentan group (309.7±96.3m (Commencement), 317.0±126.1m (Week 12), 307.0±84.4m (Week 24); p=0.86), but almost reached statistical significance in the placebo group from 328.8±79.6m, to 361.6±98.2m and 384.0±74.9m (Week 24); p=0.075. In the placebo group, estimated systolic pulmonary artery pressure (measured via echocardiography) significantly decreased (from 62.3±16.7mmHg [Commencement], 45.3±13.9mmHg [Week 12], to 44.6±14.5mmHg [Week 24]; p=0.014) as did right atrial pressure (13.1±5.3 [Commencement], 10.0±3.8 [Week 12], to 9.4±3.2 [Week 24]; p=0.046). CONCLUSION: Despite this study's limited sample size and premature cessation, it nevertheless suggests that endothelin receptor blockade in patients with PH-HFpEF may have no beneficial effects and could even be detrimental in comparison to a placebo.
Authors: Anna Klinke; Torben Schubert; Marion Müller; Ekaterina Legchenko; Jason G E Zelt; Tsukasa Shimauchi; L Christian Napp; Alexander M K Rothman; Sébastien Bonnet; Duncan J Stewart; Georg Hansmann; Volker Rudolph Journal: Cardiovasc Diagn Ther Date: 2020-10
Authors: Jason M Elinoff; Richa Agarwal; Christopher F Barnett; Raymond L Benza; Michael J Cuttica; Ahmed M Gharib; Michael P Gray; Paul M Hassoun; Anna R Hemnes; Marc Humbert; Todd M Kolb; Tim Lahm; Jane A Leopold; Stephen C Mathai; Vallerie V McLaughlin; Ioana R Preston; Erika B Rosenzweig; Oksana A Shlobin; Virginia D Steen; Roham T Zamanian; Michael A Solomon Journal: Am J Respir Crit Care Med Date: 2018-07-15 Impact factor: 21.405
Authors: Ovidiu Chioncel; Sean P Collins; Andrew P Ambrosy; Peter S Pang; Elena-Laura Antohi; Vlad Anton Iliescu; Aldo P Maggioni; Javed Butler; Alexandre Mebazaa Journal: Am J Ther Date: 2018 Jul/Aug Impact factor: 2.688
Authors: Longfei Wang; Gunner Halliday; Joshua R Huot; Taijyu Satoh; Jeffrey J Baust; Amanda Fisher; Todd Cook; Jian Hu; Theodore Avolio; Dmitry A Goncharov; Yang Bai; Rebecca R Vanderpool; Robert V Considine; Andrea Bonetto; Jiangning Tan; Timothy N Bachman; Andrea Sebastiani; Charles F McTiernan; Ana L Mora; Roberto F Machado; Elena A Goncharova; Mark T Gladwin; Yen-Chun Lai Journal: Arterioscler Thromb Vasc Biol Date: 2020-04-09 Impact factor: 8.311