EFFECT OF EXTENDED-RELEASE ISOSORBIDE MONONITRATE ONE-HOUR AFTER DOSING IN PATIENTS WITH STABLE ANGINA-PECTORIS

The effect of extended-release isosorbide mononitrate (ER-ISMN) on exe rcise tolerance 1 hour after dosing was compared with that of placebo in a multicenter, randomized, double-blind study of 151 patients with stable effort-induced angina. During a 9- to 24-day placebo run-in, pa tients underwent Bruce protocol baseline exercise tolerance tests, aft er which they received ER-ISMN or placebo for 5 days. ER-ISMN patients teak 60 mg each morning for the first. 4 days and 120 mg on the morni ng of the fifth day. One hour after dosing, ER-ISMN patients held a si gnificantly greater increase in total exercise time (days 1 to 4: 5 +/ - 53 seconds; day 5: 53 +/- 58 seconds) than the placebo-treated patie nts (days 1 to 4: 14 +/- 37 seconds; day 5: 21 +/- 48) tp <0.001), The times to development of angina and l-mm ST-segment depression were si gnificantly longer in the ER-ISMN group than in the placebo group. The difference between the groups in mean time to onset of angina was 34 seconds after the 60-mg dose (p = 0.004) and 49 seconds after the 120- mg dose (p <0.001). The mean time to development of a l-mm ST-segment depression was 51 and 61 seconds longer after the 60-mg and 120-mg ER- ISMN doses, respectively, than after placebo (p <0.001). Treatment-rel ated adverse events were reported in 37% (28 of 75) and 7% (5 of 76) o f patients in the ER-ISMN and placebo groups, respectively. As expecte d, headache was more frequent in the ER-ISMN group than in the placebo group (28% and 1%, respectively). The effects of ER-ISMN (60 mg and 1 20 mg) are clinically evident 1 hour after dosing, resulting in better exercise tolerance in patients with angina pectoris. (C) 1997 by Exce rpta Medico, Inc.