COMPARISON OF CONTINUOUS AND INTERMITTENT TREATMENT OF STABLE EFFORT ANGINA USING TRANSDERMAL NITROGLYCERIN

The anti-angina efficacy of the continuous (C) transdermal application of nitroglycerin may lessen or disappear over the course of time. Pha rmacological tolerance, which is probably responsible, might be preven ted by intermittent (1) application. However few studies have compared the C and I methods. The effects of transdermal patches containing 10 mg, applied for 24 hours/day and for 15 hours/day for one week were e valuated in twelve patients. Exercise tests were performed before and 4 hours after the initial application and after one week of each type of treatment prescribed in random order with a 7 day wash-out between each treatment phase. Plasma nitroglycerin concentrations were measure d at the same time. Total work and ischemia and angina thresholds afte r 4 hours application all increased significantly in comparison with b aseline values. All these values persisted after one week of I treatme nt. With C treatment they decreased though remained significantly abov e baseline values with the exception of angina thresholds. I treatment appeared significantly better than C treatment regarding ischemia thr eshold (3974.7 kpm v. 3 037.5 - p < 0.01). Plasma nitroglycerin levels were the same during each treatment phase. These results suggest that the anti-ischemic efficacy of transdermal patches persists after one week of treatment, though with superiority of intermittent treatment. Continuous treatment tends to induce pharmacodynamic tolerance since t here was no difference in plasma nitroglycerin levels.