Reduction in mortality by pharmacological therapy in congestive heart failure

Mortality in congestive heart failure remains high. In analysis of heart failure in the perspective of pathophysiological mechanisms, some approaches to treatment to improve survival become particularly interesting. The concept of unloading myocardial performance by reducing systemic vascular resistance has received general acceptance. This approach was associated with improved survival with nitrates and hydralazine in the V-HeFT I study. Stimulation of the myocardium in excess of what is achieved by endogenous stimulation might be dangerous. Long-term therapy with positive inotropic agents, therefore, is not an appropriate approach at present. However, addition of beta-blockers may protect the myocardium from the intense endogenous sympathetic stimulation in congestive heart failure. There are favorable trends with this approach in several small trials. An ongoing trial in idiopathic dilated cardiomyopathy may help to clarify this question. Counteraction of neuroendocrine activation may also be obtained by the addition of an angiotensin converting enzyme inhibitor. The CONSENSUS I study demonstrated a clear improvement in survival among very compromised patients by addition of enalapril. A positive effect was significantly associated with the degree of neuroendocrine activation at baseline. Two recent large-scale trials have emphasized the importance of adding an angiotensin converting enzyme inhibitor to other treatments in patients with mild to moderate symptoms and left ventricular dysfunction. These trials also support the importance of myocardial protection from neuroendocrine stimulation with symptomatic or asymptomatic myocardial failure. Antiarrhythmic agents have not been documented to improve survival. On the contrary, class I agents are deleterious in some patients with left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)