INTERMITTENT TRANSDERMAL NITROGLYCERIN THERAPY IN ANGINA-PECTORIS - CLINICALLY EFFECTIVE WITHOUT TOLERANCE OR REBOUND

Background The objectives of this study were to assess the antianginal and anti-ischemic effects of three dose levels of transdermal nitrogl ycerin patches applied for 12 hours daily for 30 days. The study also assessed the development of tolerance and rebound. Intermittent transd ermal nitroglycerin therapy with a patch-free period of 10 to 12 hours each day has documented clinical benefits during the period of patch application, but studies have failed to clearly document prolonged exe rcise duration for the entire period of patch application. This study was designed to evaluate the efficacy and duration of action of a rang e of doses of nitroglycerin. The study also permitted the assessment o f the maintenance of initial effects, the development of tolerance, an d the presence of rebound. Methods and Results This study was a multic enter, randomized, double-blind, placebo-controlled parallel design tr ial with treadmill exercise tests at days 0, 1, 7, 15, and 30. Tests w ere carried out up to 12 hours after patch application. There was a st atistically significant treatment effect with increases in treadmill w alking time to moderate angina in each nitroglycerin patch group compa red with placebo at various time points up to 12 hours throughout the 30-day study period. Secondary efficacy parameters, including the cons istent increase in time to 1-mm ST-segment depression, supported the p rimary efficacy results. There was no evidence of tolerance or rebound . Conclusions Intermittent transdermal nitroglycerin therapy increases exercise duration and maintains anti-ischemic effects for 12 hours af ter parch application, throughout 30 days of therapy, without signific ant evidence of nitrate tolerance or rebound phenomena.