Effects of Angiotensin-converting Enzyme Inhibitor Plus Irbesartan on Maximal and Submaximal Exercise Capacity and Neurohumoral Activation in Patients with Congestive Heart Failure

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.