Mechanisms of action and efficacy of nitrates in heart failure

Nitrates exert hemodynamic and possibly nonhemodynamic effects that result in reduced cardiac filling pressures, increased cardiac output, reduced pulmonary vascular pressures, and improvement in symptoms and exercise tolerance in patients with heart failure. Combined with hydralazine, chronic oral administration of isosorbide dinitrate has been demonstrated to improve survival when added to digoxin and diuretic therapy. A long-term improvement in left ventricular ejection fraction in these clinical studies has raised the possibility that the nitrates may be acting at least in part by inhibiting left ventricular remodeling. The precise role of nitrates and the optimal dosing regimen in the therapeutic armamentarium for heart failure, particularly in patients already treated with a converting enzyme inhibitor, remains to be established.