THERAPY OF LEFT-VENTRICULAR DYSFUNCTION - IMPLICATIONS OF RECENT THERAPEUTIC TRIALS AND FUTURE-DIRECTIONS FOR THERAPY

The natural history of patients with heart failure has changed relatively little until recently. Several large randomized trials have however recently changed our approach to the patient with symptomatic as well as asymptomatic left ventricular dysfunction. Although the effect of digoxin on survival is still uncertain there is still good evidence from the Radiance study in which patients were randomly withdrawn from digoxin that patients who remain on digoxin have a significant improvement in exercise tolerance and well being. The Concensus trial in patients with class IV heart failure suggested that ACE inhibitors were effective in improving survival. This therapy has not however been widely adapted in patients with mild to moderate heart failure. The recent randomized SOLVD treatment trial in conjunction with the VHEFT II study clearly shows that ACE inhibitors should be the basis for therapy along with a diuretic and digoxin if necessary in all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. There is also evidence from the SOLVD prevention trial that ACE inhibitors can prevent the development of manifest heart failure and hospitalization for heart failure in patients with asymptomatic left ventricular dysfunction. The importance of ACE inhibitors in patients with asymptomatic left ventricular dysfunction is confirmed by data from the SAVE trial which examine both symptomatic and asymptomatic patients with left ventricular dysfunction 3-16 days post infarction. Of interest in both the SOLVD treatment and prevention trials as well as the SAVE trial was the finding that ACE inhibitors reduced the incidence of recurrent ischemic events. These trials suggest that ACE inhibitors will have an important role in patients with asymptomatic as well as symptomatic left ventricular dysfunction and possibly play an important role in the secondary prevention of ischemic heart disease. Although ACE inhibitors have significantly reduced mortality in patients with symptomatic left ventricular dysfunction there remains a relatively high risk of recurrent failure and death in these patients. There are a number of new strategies that need to be explored to further reduce morbidity and mortality in patients with systolic left ventricular dysfunction.