title: Determinants of blood pressure reduction by eplerenone in uncontrolled hypertension.
abstract: BACKGROUND
  Add-on therapy with aldosterone receptor antagonists has been reported to lower blood pressure (BP) in patients with uncontrolled hypertension. We assessed potential predictors of this response.
  
  
  METHODS
  In essential hypertensive patients with uncontrolled BP, despite the use of at least two antihypertensives, plasma renin and aldosterone concentrations and the transtubular potassium gradient (TTKG) were measured. Patients were treated with eplerenone 50 mg daily on top of their own medication. The office and ambulatory BP response and biochemical changes were evaluated after 1 week and 3 months of treatment and 6 weeks after discontinuation. Potential predictors for the change in 24-h ambulatory BP were tested in a multivariate regression model.
  
  
  RESULTS
  One hundred and seventeen patients with a mean age of 50.5 ± 6.6 years were included. Office BP decreased from 149/91 to 142/87 mmHg (P < 0.001) and ambulatory BP from 141/87 to 132/83 mmHg after 3 months of treatment (P < 0.001). Six weeks after discontinuation of eplerenone, office and ambulatory BP measurements returned to baseline values. Treatment resulted in a small rise in serum potassium and creatinine, and a small decrease in the TTKG. In a multivariate model, neither renin, aldosterone, or their ratio, nor the TTKG predicted the BP response. Only baseline ambulatory SBP predicted the BP response, whereas the presence of left ventricular hypertrophy was associated with a smaller BP reduction.
  
  
  CONCLUSIONS
  Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension. This effect is unrelated to circulating renin-angiotensin-aldosterone system activity and renal mineralocorticoid receptor activity as assessed by the TTKG.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Pieter M
authors.initials: PM
authors.lastname: Jansen
authors.forename: Wijnanda J
authors.initials: WJ
authors.lastname: Frenkel
authors.forename: Bert-Jan H
authors.initials: BJ
authors.lastname: van den Born
authors.forename: Emile L E
authors.initials: EL
authors.lastname: de Bruijne
authors.forename: Jaap
authors.initials: J
authors.lastname: Deinum
authors.forename: Michiel N
authors.initials: MN
authors.lastname: Kerstens
authors.forename: Joyce H A
authors.initials: JH
authors.lastname: Arnoldus
authors.forename: Arend Jan
authors.initials: AJ
authors.lastname: Woittiez
authors.forename: Johanna A M
authors.initials: JA
authors.lastname: Wijbenga
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
mesh_terms: D000328:Adult; D001794:Blood Pressure; D000077545:Eplerenone; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone