Activation of the renin–angiotensin–aldosterone system is an important mechanism in the pathophysiology of heart failure as part of the counter-regulatory neurohormonal response to impaired cardiac output. In conjunction with sympathetic drive, there is an increase in peripheral vasoconstriction mediated by increased sympathetic tone and angiotensin II coupled with the salt and water retention induced by elevated aldosterone concentrations. Together, these increase preload and afterload on the heart, further compromising impaired ventricular function and setting up a vicious circle of heart failure.

Angiotensin–converting enzyme inhibitor drugs (ACE inhibitors) block this increase in aldosterone production and are effective drugs in the clinical management of chronic heart failure. In randomized controlled trials, ACE inhibitors have been shown to improve symptoms and reduce the incidence of further cardiac events including hospital readmission for heart failure, myocardial infarction and death.