Determination of the optimal dose of glyceryl trinitrate in the treatment of stable angina.

There has been recent controversy over the efficacy of transdermal glyceryl trinitrate (GTN) preparations in the treatment of angina and their effects on exercise tolerance. To determine the dose of GTN that produces significant anti-anginal effects, symptom limited exercise testing has been undertaken in seven patients with stable angina. Doses of 10, 20, 40 and 80 micrograms min-1 of GTN or placebo were infused during treadmill exercise until symptom limiting chest pain or greater than or equal to 3 mm ST segment depression occurred. Compared with placebo, total exercise time increased by 47% at 20 micrograms min-1 (P less than 0.05) with no further change at the higher doses. Duration of exercise before the onset of significant ST segment depression increased by 51% at 20 micrograms min-1 (P less than 0.05) with no further increase at the higher doses. These changes were accompanied by a 21% increase in double product (heart rate X systolic blood pressure) at 20 micrograms min-1 (P less than 0.05) reflecting a higher heart rate achieved as a result of the increased duration of exercise. These results suggest that 20 micrograms min-1 may be the optimal dose of GTN to achieve significant antianginal effects as demonstrated by the improved exercise tolerance and reduction of myocardial ischaemia. This implies that the dose of GTN delivered by transdermal preparations may be below the therapeutic level.