Andreas Tomaschitz1, Nicolas Verheyen, Andreas Meinitzer, Burkert Pieske, Evgeny Belyavskiy, Helmut Brussee, Josef Haas, Winfried März, Elisabeth Pieske-Kraigher, Sarah Verheyen, Lisa Ofner-Ziegenfuss, Bríain Ó Hartaigh, Verena Schwetz, Felix Aberer, Martin Grübler, Florian Lang, Ioana Alesutan, Jakob Voelkl, Martin Gaksch, Jörg H Horina, Hans-Peter Dimai, Jutta Rus-Machan, Claudia Stiegler, Eberhard Ritz, Astrid Fahrleitner-Pammer, Stefan Pilz. 1. aSpecialist Clinic for Rehabilitation Bad Aussee, Bad Aussee bDepartment of Cardiology cClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria dDepartment of Internal Medicine - Cardiology, Charité University Hospital Berlin, Campus Virchow Klinikum eDeutsches Herzzentrum, Berlin, Germany fDepartment of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria gSynlab Academy, Synlab Services LLC, Mannheim hVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany iInstitute of Human Genetics, Medical University of Graz, Graz, Austria jDepartment of Radiology, Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and the Weill Cornell Medical College, New York, New York kDepartment of Internal Medicine, Section of Geriatrics, Yale School of Medicine, Adler Geriatric Center, New Haven, Connecticut, USA lDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria mSwiss Cardiovascular Center Bern, Department of Cardiology, Bern University Hospital, Bern, Switzerland nDepartment of Physiology, University of Tübingen, Tübingen, Germany oDepartment of Internal Medicine, Division of Nephrology pOffice of the Vice Rector for Teaching and Studies, Medical University of Graz, Graz, Austria qDepartment of Medicine, Division of Nephrology, University Hospital Heidelberg, Heidelberg, Germany rDepartment of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands *Nicolas Verheyen and Stefan Pilz contributed equally to the writing of this article as first authors.
Abstract
BACKGROUND: Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT). METHODS: The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions]. RESULTS:We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration ratemore than 50 ml/min per 1.73 m. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks.The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9-1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) -6.3 (-9.4 to -3.3) and -3.7 (-5.7 to -1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events. CONCLUSION: In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.
RCT Entities:
BACKGROUND: Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT). METHODS: The Eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism (EPATH) trial is a single-center, randomized, double-blind, parallel-group, placebo-controlled trial. The primary aim is to evaluate the effects of the mineralocorticoid receptor antagonist eplerenone on plasma intact PTH (iPTH) concentration in patients with pHPT. Secondary end points comprised surrogate parameters of cardiovascular health [24-h ambulatory SBP and DBP and echocardiographic parameters related to systolic/diastolic function as well as to cardiac dimensions]. RESULTS: We enrolled 110 study participants with pHPT, 25-hydroxyvitamin D at least 20 ng/ml and estimated glomerular filtration rate more than 50 ml/min per 1.73 m. Patients were 1 : 1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or matching placebo for a treatment period of 8 weeks.The study was completed by 97 participants [mean (SD) age: 67.5 ± 9.5 years; 78.4% women). The mean treatment effect (95% confidence interval) for iPTH was 1.0 (0.9-1.1; P = 0.777) pg/ml. Mean 24-h ambulatory SBP and DBP decreased significantly [mean change (95% confidence interval) -6.3 (-9.4 to -3.3) and -3.7 (-5.7 to -1.7) mmHg, respectively; P < 0.001]. No differences were seen in any further secondary outcomes or frequency of adverse events. CONCLUSION: In pHPT, treatment with eplerenone compared with placebo had no effect on circulating iPTH levels. Eplerenone treatment was well tolerated and safe and followed by significant decrease of ambulatory blood pressure.
Authors: Julia Wetzel; Stefan Pilz; Martin R Grübler; Astrid Fahrleitner-Pammer; Hans P Dimai; Dirk von Lewinski; Ewald Kolesnik; Sabine Perl; Christian Trummer; Verena Schwetz; Andreas Meinitzer; Evgeny Belyavskiy; Jakob Völkl; Cristiana Catena; Vincent Brandenburg; Winfried März; Burkert Pieske; Helmut Brussee; Andreas Tomaschitz; Nicolas D Verheyen Journal: J Clin Hypertens (Greenwich) Date: 2017-08-20 Impact factor: 3.738
Authors: Sarah Zaheer; Jenifer M Brown; Molly Connors; Jonathan S Williams; Gail K Adler; Anand Vaidya Journal: Int J Endocrinol Date: 2017-07-20 Impact factor: 3.257
Authors: Nicolas Verheyen; Astrid Fahrleitner-Pammer; Evgeny Belyavskiy; Martin R Gruebler; Hans Peter Dimai; Karin Amrein; Klemens Ablasser; Johann Martensen; Cristiana Catena; Elisabeth Pieske-Kraigher; Caterina Colantonio; Jakob Voelkl; Florian Lang; Ioana Alesutan; Andreas Meinitzer; Winfried März; Helmut Brussee; Burkert Pieske; Stefan Pilz; Andreas Tomaschitz Journal: PLoS One Date: 2017-04-13 Impact factor: 3.240
Authors: Ana Paula Santana Gueiros; José Edevanilson de Barros Gueiros; Karina Tavares Nóbrega; Eveline Barros Calado; Marina Cadena da Matta; Leuridan Cavalcante Torres; Alex Sandro Rolland Souza; Dulce Elena Casarini; Aluizio Barbosa de Carvalho Journal: J Bras Nefrol Date: 2019-08-15