title: Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure.
abstract: BACKGROUND
  In patients with symptomatic congestive heart failure receiving optimal therapy with an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker, the impact of using an angiotensin receptor blocker on submaximal exercise capacity and on neurohumoral activation at rest and during stress has not been investigated.
  
  
  METHODS
  Thirty-three patients with congestive heart failure, New York Heart Association II or III symptoms, and left ventricular ejection fraction 25.5% +/- 7.2% treated with an ACE inhibitor and a beta-blocker were recruited. Patients were randomly assigned to receive irbesartan 150 mg per day (n = 22) or a placebo (n = 11) for 6 months. Maximal exercise capacity was assessed using a ramp protocol. Submaximal exercise duration was assessed using a constant load protocol, and plasma norepinephrine and angiotensin II (A-II) were measured in resting state, at 6 minutes, and at peak exercise.
  
  
  RESULTS
  Patients treated with irbesartan presented a 26% increase in submaximal exercise time (+281 seconds, P = .08) whereas exercise duration increased by only 7% in patients treated with a placebo (+128 seconds, P = NS irbesartan vs placebo). Norepinephrine levels increased to a similar extent in both groups, whereas A-II levels did not increase or change in response to therapy.
  
  
  CONCLUSIONS
  Dual A-II suppression with an ACE inhibitor plus irbesartan provides a small but a significant increase in submaximal exercise capacity. This beneficial effect is observed despite no significant changes in maximal exercise capacity, and in resting or exercise-induced increase in neurohumoral activation.
authors.affiliation: Department of Medicine, Division of Cardiology, Montreal Heart Institute, Montreal, Quebec, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Blanchet
authors.forename: Richard
authors.initials: R
authors.lastname: Sheppard
authors.forename: Normand
authors.initials: N
authors.lastname: Racine
authors.forename: Anique
authors.initials: A
authors.lastname: Ducharme
authors.forename: Daniel
authors.initials: D
authors.lastname: Curnier
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Tardif
authors.forename: Pierre
authors.initials: P
authors.lastname: Sirois
authors.forename: Marie-Catherine
authors.initials: MC
authors.lastname: Lamoureux
authors.forename: Jacques
authors.initials: J
authors.lastname: De Champlain
authors.forename: Michel
authors.initials: M
authors.lastname: White
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077405:Irbesartan; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011446:Prospective Studies; D012146:Rest; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D019344:Lactic Acid; D004656:Enalapril; D000077405:Irbesartan; D009638:Norepinephrine