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 p-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 = .018) 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.