High-dose isosorbide dinitrate in management of angina pectoris

The hypothesis was tested that selected patients with coronary artery disease whose rate of angina attacks do not respond to low doses of isosorbide dinitrate (ISDN) (40 mg/day) may respond to high doses (480 mg/day), tolerate them, and maintain their responsiveness over the long term. Twenty-four patients with grade 3 stable angina pectoris were given a placebo for 4 weeks and then had their ISDN dosages titrated up to 120 mg four times a day during another 6 weeks in a single-blind fashion. The 20 patients who responded to (and tolerated) a high dose of ISDN were maintained at that dose for an average of 1 year. The weekly rate of angina attacks fell by 74%, from 6.05 during placebo to 1.6 (p less than 0.01) during long-term ISDN treatment. Nitroglycerin consumption fell similarly. Patient assessment of activity level, well-being, and angina threshold improved in the majority of patients. The within-patient trend of their weekly rate of angina episodes was stable in 13 patients, downward in six, and upward in only one patient. Exercise performance evaluated by a submaximal graded multistage treadmill test showed a small but nonsignificant improvement of 1.8%. It is concluded that (1) some patients who do not respond to the antianginal action of low-dose ISDN may respond to a high dose and tolerate it, (2) this responsiveness and tolerability may last for over a year, and (3) ISDN may be clinically useful in patients with coronary disease even when exercise performance is not significantly improved.