Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure

Am Heart J. 2005 May;149(5):938.e1-7. doi: 10.1016/j.ahj.2004.11.011.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Biphenyl Compounds / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Enalapril / therapeutic use
  • Exercise Tolerance / drug effects*
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Humans
  • Irbesartan
  • Lactic Acid / blood
  • Male
  • Middle Aged
  • Norepinephrine / blood*
  • Prospective Studies
  • Rest
  • Tetrazoles / therapeutic use*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biphenyl Compounds
  • Tetrazoles
  • Angiotensin II
  • Lactic Acid
  • Enalapril
  • Irbesartan
  • Norepinephrine