title: Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial.
abstract: BACKGROUND
  Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure.
  
  
  RESULTS
  Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150+/-160 pg/mL, mean+/-SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL, mean+/-SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8+/-3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor beta-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs.
  
  
  CONCLUSIONS
  Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, 420 Delaware St SE, Minneapolis, Minn 55455, USA. cohnx001@umn.edu
authors.forename: Jay N
authors.initials: JN
authors.lastname: Cohn
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Yann-Tong
authors.initials: YT
authors.lastname: Chiang
authors.forename: Robert
authors.initials: R
authors.lastname: Glazer
mesh_terms: D000450:Aldosterone / Q000097:blood*; D057911:Angiotensin Receptor Antagonists; D002303:Cardiac Output, Low / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D002908:Chronic Disease; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D013777:Tetrazoles; D000450:Aldosterone; D000068756:Valsartan; D014633:Valine