Converting-Enzyme Inhibition in the Management of Severe Chronic Congestive Heart Failure

Abstract

Evidence from the experimental and clinical laboratory suggests that the heart failure state is characterized not only by an excessive degree of systemic vasoconstriction but also by an exaggerated neurohormonal response to the decline in cardiac performance. Therapeutic interventions directed only at the first abnormality may serve to exacerbate the second, and thus may fail to produce long-term hemodynamic and clinical benefits. Converting-enzyme inhibitors successfully antagonize both homeostatic malfunctions, and thus are among the few vasodilators that have been shown to produce consistent circulatory and symptomatic improvement in patients with severe chronic heart failure in controlled clinical trials; the responses to treatment with these agents have been superior to those seen during therapy with placebo or other vasodilator drugs. Furthermore, experimental and clinical evidence suggests that converting-enzyme inhibitors exert favorable effects on the survival of patients with severe heart failure; this potential has now been confirmed in a large-scale, multicenter, placebo-controlled trial. Despite its benefits, converting-enzyme inhibition may be accompanied by adverse circulatory and metabolic reactions (symptomatic hypotension, renal insufficiency, and potassium retention), which are predictable consequences of interference with the homeostatic role of angiotensin II in low-output states.