Clinical benefit of transdermal glyceryl trinitrate when used with an eight hour patch-free period

The 24-hour application of transdermal nitrate patches has been associated with rapid development of therapeutic tolerance. Recent reports suggest maintenance of clinical benefit by introducing a daily patch-free period. This study investigates, by means of serial treadmill testing, the efficacy of a new transdermal delivery system when used with an eight hour patch-free period in 16 subjects with chronic stable angina. Concomitant antianginal therapy was permitted. After demonstration of exercise test reproducibility and nitrate responsiveness, subjects entered a double-blind randomised placebo-controlled crossover trial comprising one week of active nitroglycerin patches (10mg/24hrs) and one week of an identical placebo patch. Exercise tests were conducted four hours after patch application on the last day of each of the treatment arms. Daily angina frequency and nitroglycerin consumption were also monitored. There was significant improvement in total exercise duration (16.5%), time to onset of angina (26%), time to 1mm ST depression (22%), and peak heart rate blood pressure product with active patch application. Angina frequency was reduced during the week of active therapy. These results demonstrate the additional efficacy of intermittent transdermal nitroglycerin in a group of subjects with continuing angina despite therapy with beta-blockers and calcium antagonists.