Role of nitroglycerin in effort angina

The use of nitroglycerin in the treatment of effort angina has two facets (1) relief of established episodes of angina, and (2) prophylaxis to enhance exercise capacity. To produce relief of angina in a substantial proportion of patients, a nitrate preparation must begin to have an effect within two minutes or less. Such rapid onset has been documented only with sublingual nitroglycerin, inhaled amyl nitrate, and two new preparations: nitroglycerin spray and sustained release transmucosal nitroglycerin. Prophylactic effects of nitrates are best assessed and compared using double-blind, placebo-controlled exercise testing at multiple time points after the administration of carefully titrated matched doses. A bicycle ergometer protocol devised at the National Heart, Lung and Blood Institute has been widely used for this purpose and permits comparison of various "long-acting" nitrates at doses that produce peak effects comparable to conventional doses of sublingual nitroglycerin. Oral isosorbide dinitrate and 2 percent nitroglycerin ointment enhance effort tolerance for up to three hours after administration, whereas sustained release transmucosal nitroglycerin produces such effects for up to five hours. Similar clinical efficacy data are lacking for the new cutaneous nitroglycerin patches. In clinical use, larger doses of nitroglycerin in any form may produce more marked and prolonged prophylactic effects. Despite the availability of multiple new antianginal agents of the calcium antagonist and beta blocker types, nitroglycerin continues to be a mainstay of antianginal therapy and is likely to remain so for the foreseeable future. However, new high dose prolonged effect regimens raise important questions about the frequency and clinical significance of nitrate tolerance.