Conceptual dilemmas in the classification of vasodilator drugs for severe chronic heart failure. Advocacy of a pragmatic approach to the selection of a therapeutic agent

Two distinct systems of classifying vasodilator drugs have been developed over the past decade in an attempt to guide the choice of a therapeutic agent for the patient with severe heart failure, but the merits and utility of these systems have not been critically evaluated. Vasodilator drugs may be categorized according to their peripheral site of action: an agent may exert its effects preferentially on systemic arteries, systemic veins, or on both circulations. However, changes in the peripheral circulation cannot be directly translated into an improvement in central hemodynamic variables; furthermore, immediate hemodynamic responses may not be predictive of long-term clinical efficacy. Hence, there is no evidence that characterization of patients into hemodynamic subsets determined by the findings of right heart catheterization improves the clinical outcome of vasodilator therapy in chronic heart failure. An alternative classification system groups vasodilator drugs according to their mechanism of action: an agent may possess direct vasodilating effects or may exert its actions via selective neurohumoral inhibition. However, attempts to identify patients who might be most responsive to neurohumoral antagonism by measuring plasma renin activity or circulating levels of catecholamines before treatment have not been successful in predicting the clinical responses to therapy. Because neither system of drug classification provides the clinician with useful therapeutic guidelines, patients with severe heart failure appear to be best managed using a pragmatic approach in which specific drugs that produce predictable therapeutic benefits with a low frequency of side effects are utilized preferentially. Among presently available vasodilator agents, only captopril and oral isosorbide dinitrate have been shown to produce consistent hemodynamic and clinical improvement with an acceptable degree of adverse reactions.