Abstract
In a randomized, double blind, crossover study, 10 patients with stable exercise-induced angina pectoris were studied during acute and sustained therapy with oral isosorbide dinitrate. Circulatory changes and exercise performance were evaluated before and 2 and 6 hours after medication. Sublingual nitroglycerin was administered 30 minutes after the 2 and 6 hour exercise tests and the exercise test was repeated after another 5 minutes. Systolic blood pressure at rest 2 hours after isosorbide dinitrate decreased by 25% during the acute phase, but by only 11% during the sustained phase (probability [p] < 0.05). Systolic blood pressure was not decreased further by nitroglycerin during acute therapy, but was decreased during sustained therapy (p < 0.05). Six hours after isosorbide dinitrate administration, systolic blood pressure remained significantly below the control value during sustained therapy. Treadmill walking time to moderate angina was significantly prolonged 2 hours after isosorbide dinitrate administration during both the acute and sustained phases. During the sustained phase, there was no difference from control values after 6 hours. Nitroglycerin did not increase walking time 2 1/2 hours after isosorbide dinitrate during either acute (567 ± 122 versus 560 ± 119 seconds) or sustained (582 ± 115 versus 567 ± 129 seconds) therapy, but at 6 1/2 hours, nitroglycerin increased walking time from 473 ± 125 to 547 ± 107 seconds (p < 0.05) during sustained therapy. This study demonstrates that 1) tolerance to the hemodynamic and antianginal effects of isosorbide dinitrate develops rapidly, 2) nitroglycerin does not further prolong exercise duration 2 1/2 hours after isosorbide dinitrate administration, 3) nitroglycerin prolongs exercise duration when isosorbide dinitrate is no longer exerting a beneficial effect, and 4) there is possible cross-tolerance between isosorbide dinitrate and nitroglycerin.
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