title: Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: results from the EPATH randomized, placebo-controlled trial.
abstract: Accumulating evidence points toward mutual interaction between parathyroid hormone (PTH) and aldosterone as potential mechanism for increasing cardiovascular risk in primary hyperparathyroidism (pHPT).
  
  
  
  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].
  
  
  
  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.
  
  
  
  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.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Tomaschitz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Verheyen
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.forename: Evgeny
authors.initials: E
authors.lastname: Belyavskiy
authors.forename: Helmut
authors.initials: H
authors.lastname: Brussee
authors.forename: Josef
authors.initials: J
authors.lastname: Haas
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pieske-Kraigher
authors.forename: Sarah
authors.initials: S
authors.lastname: Verheyen
authors.forename: Lisa
authors.initials: L
authors.lastname: Ofner-Ziegenfuss
authors.forename: Bríain Ó
authors.initials: BÓ
authors.lastname: Hartaigh
authors.forename: Verena
authors.initials: V
authors.lastname: Schwetz
authors.forename: Felix
authors.initials: F
authors.lastname: Aberer
authors.forename: Martin
authors.initials: M
authors.lastname: Grübler
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.forename: Martin
authors.initials: M
authors.lastname: Gaksch
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Horina
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Dimai
authors.forename: Jutta
authors.initials: J
authors.lastname: Rus-Machan
authors.forename: Claudia
authors.initials: C
authors.lastname: Stiegler
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Astrid
authors.initials: A
authors.lastname: Fahrleitner-Pammer
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D003971:Diastole; D004311:Double-Blind Method; D004452:Echocardiography; D000077545:Eplerenone; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000097:blood* / Q000188:drug therapy*; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood*; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013599:Systole; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010281:Parathyroid Hormone; D014807:Vitamin D; D013148:Spironolactone; D000077545:Eplerenone; C104450:25-hydroxyvitamin D