High-dosage isosorbide dinitrate therapy for angina.

We investigated the possibility that high dosages (480 mg/d) of isosorbide dinitrate might reduce the frequency of angina attacks in selected patients who had not responded to low dosages of the drug (40 mg/d), and that the patients could tolerate the high levels of medication and maintain their responsiveness over the long term. In the single-blind phases of this trial 24 patients with grade 3 stable angina pectoris were given a placebo for 4 weeks and then increasing doses of isosorbide dinitrate for a further 6 weeks. The 19 patients who both responded to and tolerated high doses of the drug kept taking 480 mg/d for an average of 1 year. The average weekly rate of angina attacks fell by 74%, from 6.05 in the placebo phase to 1.6 during long-term active treatment (p less than 0.01). Nitroglycerin consumption decreased accordingly. The patients' assessments of their levels of activity and well-being and their angina thresholds showed improvement among most of them. The trend of angina frequency was stable in 12 cases, downward in 6 and upward in only 1 case. Exercise performance as evaluated by a graded treadmill test showed a small but nonsignificant improvement of 18%. It was concluded that some patients who do not respond to the antianginal action of low-dosage isosorbide dinitrate and cannot be given beta-blockers may respond to high dosages and tolerate them for over a year. Isosorbide dinitrate may be clinically useful in patients with coronary heart disease even though their exercise performance is not significantly improved.