Antiischaemic effects of phasic release nitroglycerin system during acute and sustained therapy

A newly developed glyceryl trinitrate (GTN) patch with biphasic release (7.5 mg GTN (24h)-1) was compared with placebo in 40 patients with stable angina pectoris, in a double-blind randomized crossover study. Exercise tests employing a bicycle ergometer were carried out 2 and 10h after application of the patch on the first day and after 7 days of continuous therapy and 2h after patch reapplication at the end of a 3-month period of once daily therapy. In comparison with placebo, 2h after acute dosing, ST-segment depression was decreased from 0.15 mV to 0.07 mV (P less than 0.001), the time to 0.1 mV ST-segment depression was increased from 3.6 to 5.0 min (P less than 0.001) and work capacity was increased from 280 W min-1 to 446 W min-1 (P less than 0.001). After 1 week of daily GTN therapy the effects at 2h were somewhat greater than in the acute test. Compared with the values 2h after GTN patch application, the effects after 10h, both on the first day and 7th day, were substantially lower. During long-term therapy, the effects observed after 1 week of GTN therapy were maintained. The decrease in effects between 2 and 10h probably represent partial nitrate tolerance but the similar effects on the first and 7th day indicate no change during sustained therapy.