THE DAYLONG PATTERN OF THE ANTIANGINAL EFFECT OF LONG-TERM 3 TIMES DAILY ADMINISTERED ISOSORBIDE DINITRATE

Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 am, 9 am, 11 am, 1 pm, 2 pm, 4 pm, 6 pm and 7 pm. On one day each patient received isosorbide dinitrate at 8 am, 1 pm and 6 pm in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 am dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 am exercise time had returned to control level. One hour after the 1 pm dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later. At 7 pm, 1 h after the third dose of isosorbide dinitrate, exercise duration increased by only 70 s. Thus, at best, patients receiving long-term therapy with isosorbide dinitrate three times daily obtain a total of no more than 6 h of antianginal benefit during a 24 h period, and the magnitude of the benefit declines with each succeeding dose during the day. © 1990, American College of Cardiology Foundation. All rights reserved.