Nitrates versus angiotensin-converting enzyme inhibitors for congestive heart failure

The efficacy of nitrates versus that of angiotensin-converting enzyme (ACE) inhibitors in heart failure may be evaluated based on 3 treatment aims: hemodynamic improvement, symptom relief, and survival benefit. Nitrates used in conjunction with hydralazine produce a relatively large increase in stroke volume and a prominent reduction of left ventricular filling pressure, whereas ACE inhibitors produce a comparatively modest increase in stroke volume with a prominent reduction in filling pressure. The effect of these drugs on arterial compliance has been evaluated using a modified Windkessel model of the circulation to define their mechanism of action. Nitrates appear to affect the large arteries and arterial bed as well as the venous circulation. Intermediate-term response to therapy is often evaluated by changes in exercise tolerance. A review of multicenter trials reveals that, although both ACE inhibitors and hydralazine/nitrate have favorable hemodynamic actions, the effect of hydralazine/nitrate on exercise capacity appears to be slightly better. ACE inhibitors and nitrates both may reduce dysfunctional myocardial remodeling, as evaluated in a canine model of chronic left ventricular dysfunction. The increase in the ejection fraction by these drugs and the decrease of plasma norepinephrine levels by ACE inhibitors may contribute to improved long-term survival. It appears, therefore, that the long-term benefits of nitrates and ACE inhibitors in heart failure probably relate to their ability both to affect cardiac remodeling and to relax vascular smooth muscle.