Neurohormonal mechanisms and the role of angiotensin-converting enzyme (ACE) inhibitors in heart failure.

Clinical evidence accumulated over the past decade suggests that neurohormonal mechanisms significantly influence the pathogenesis and eventual outcome of congestive heart failure (CHF). Pharmacologic modulation of this neuroendocrine activity can, consequently, be expected to improve patient prognosis. Results of several recent clinical trials--the Studies of Left Ventricular Dysfunction (SOLVD), the second Veterans Administration Cooperative Vasodilator Heart Failure Trial (VH eFT-II), and the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)--provide substantial evidence that addition of the angiotensin-converting enzyme (ACE) inhibitor enalapril to conventional therapeutic regimens can significantly reduce mortality and improve prognosis in patients with all grades of heart failure. Moreover, data from all three trials confirm the involvement of neurohormonal systems in the development and progression of CHF and suggest that the beneficial effects of enalapril in heart failure may in part be due to the suppression of this neurohormonal activity. It is now apparent that some form of neurohormonal activation is present early in the course of the disease before the emergence of overt heart failure symptoms. On the basis of such findings, it would seem that early introduction of therapy targeted at neurohormonal influences may well become a central component of any future CHF treatment program.