The clinical course of heart failure and its modification by ACE inhibitors: insights from recent clinical trials.

Our understanding of the clinical course of heart failure and the mechanism by which ACE inhibitors reduce mortality and morbidity is being enhanced by recent results from large trials. The belief that heart failure constitutes a gradual progression of symptoms and signs leading eventually to death has been challenged by the finding that many patients die suddenly, before the onset of symptoms at rest. Indeed, many studies have shown that sudden death, with or without the progression of heart failure, is the most common mode of death. Studies suggest that ACE inhibitors reduce mortality in heart failure both by preventing or delaying the progression of heart failure or sudden death, and by reducing the incidence of myocardial infarction. ACE inhibitors may improve ventricular function by a variety of mechanisms, including effects on neuro-endocrine systems, haemodynamic effects, and direct actions on the myocardium. ACE inhibitors may also have a long-term effect on plaque growth or rupture, which may account for the observed reduction in the incidence of myocardial infarction. Although ACE inhibitors would be expected to lower the risk of arrhythmias, through their ability to reduce pressure and volume overload, this effect has not been observed consistently in large- scale trials. One of the most important clinical benefits of ACE inhibition may prove to be the reduction in myocardial infarction. The use of an ACE inhibitor should be considered in all patients with significantly impaired systolic left ventricular function (in the absence of contra- indications), even those who are asymptomatic, although the precise level of ventricular dysfunction at which treatment should be initiated remains to be clarified. The ability of long-term ACE inhibitor treatment to reduce ischaemic events in patients with normal left ventricular function is currently being studied. The optimum dose remains to be determined, although beneficial results have been obtained with enalapril, 20 mg daily, captopril, 150 mg daily and ramipril 5 mg b.i.d.