title: ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.
abstract: BACKGROUND
  Persistent activation of the renin-angiotensin-aldosterone-system (RAAS) is known to occur in patients with chronic heart failure (CHF) despite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone.
  
  
  METHODS
  Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were randomly assigned in a double-blind manner to receive either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF) as measured by radionuclide ventriculography, and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects.
  
  
  RESULTS
  There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo. A trend toward an increase in plasma renin activity was noted with eprosartan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged.
  
  
  CONCLUSIONS
  When added to an ACE inhibitor, eprosartan reduced arterial pressure without increasing heart rate. There was no change in LVEF after 2 months of therapy with eprosartan.
authors.affiliation: Department of Cardiology, Western Infirmary, Glasgow, UK. drm2x@udcf.gla.ac.uk
authors.forename: D R
authors.initials: DR
authors.lastname: Murdoch
authors.forename: T A
authors.initials: TA
authors.lastname: McDonagh
authors.forename: R
authors.initials: R
authors.lastname: Farmer
authors.forename: J J
authors.initials: JJ
authors.lastname: Morton
authors.forename: J J
authors.initials: JJ
authors.lastname: McMurray
authors.forename: H J
authors.initials: HJ
authors.lastname: Dargie
mesh_terms: D000179:Acrylates / Q000627:therapeutic use*; D000368:Aged; D000804:Angiotensin II / Q000097:blood*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002407:Catheterization, Swan-Ganz; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D015635:Radionuclide Ventriculography; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012083:Renin / Q000097:blood*; D012449:Safety; D013876:Thiophenes
chemical_list: D000179:Acrylates; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D015415:Biomarkers; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013876:Thiophenes; D000804:Angiotensin II; C068373:eprosartan; D009320:Atrial Natriuretic Factor; D012083:Renin; D009638:Norepinephrine