THE ROLE OF NITRATES IN CORONARY HEART-DISEASE

The organic nitrates are a safe and effective choice for the managemen t of ischemic syndromes related to coronary heart disease. Although th e anti-ischemic effects of these compounds have been recognized for mo re than a century, the mechanisms by which they exert their beneficial effects are still being delineated. In addition to their well-establi shed venodilative activity, nitrates are now known to cause vasorelaxa tion of coronary arteries, coronary stenoses, and coronary collateral vessels and to prevent episodic coronary constriction. An antiplatelet effect has also be hypothesized. The three nitrate compounds currentl y available in the United States-nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate-are provided in a variety of dosage forms, including sublingual, transmucosal, oral, and transdermal preparations . The rapid- but short-acting nitrate preparations are useful in arres ting and preventing acute attacks of angina pectoris, whereas longer-a cting oral and transdermal formulations are indicated for the relief o f chronic symptomatic and asymptomatic ischemia. The intermittent nitr ate dosing regimens introduced in recent years have reduced the likeli hood of tolerance, which greatly limited the usefulness of long-acting nitrates in the past. Intravenous infusion of nitroglycerin is partic ularly appropriate for the management of unstable angina and the early complications of acute myocardial infarction. Preliminary evidence su ggests that intravenous nitroglycerin may also be beneficial in preven ting postinfarction ventricular remodeling, although it cannot yet be recommended for this purpose.