Haemodynamic studies with a phasic release nitroglycerin patch system.

The use of transdermal nitroglycerin (GTN) patches in patients with coronary artery disease is of uncertain value as numerous investigators have failed to confirm clinical efficacy for more than 8h. This relatively short duration of action is an indication of rapidly developing tolerance due to the relatively constant GTN plasma levels following GTN patch application. We investigated the efficacy of a newly developed GTN patch with a discontinuous release profile in 28 patients with coronary heart disease. Two hours after initial administration, pulmonary capillary wedge (PCW) pressure decreased by 25.7% at rest and by 25.1% during exercise. Cardiac index at rest decreased by 12.2%. No significant changes were observed in systemic blood pressure and heart rate. No significant haemodynamic effects were apparent after 24h. Following renewed GTN patch application, a decrease in PCW pressure occurred, similar to that observed after acute administration. After 1 week of daily therapy, similar changes were observed: 24h after patch application, PCW was similar to baseline values but showed a significant decrease 2h after patch re-application. These data suggest that the phasic release GTN patch is not associated with tolerance to the haemodynamic effects during sustained once daily therapy.