Efficacy of Isosorbide 5-Mononitrate in Patients with Stable Angina Pectoris: Acute Effect and its Subsequent Attenuation

Isosorbide 5-mononitrate (IS 5-MN), an active metabolite of isosorbide dinitrate, is widely used as an antianginal agent. The acute and subacute effects of IS 5-MN, 20 mg twice daily in 8 patients and three times daily in other 8 patients with stable angina pectoris were evaluated using a placebo controlled, double blind, randomized trial protocol. There were two phases of 10 days each in which patients received placebo or active IS 5-MN. Acute testing was performed 2 hours after the morning dose on day 10. Acute testing showed a significant increase in exercise time after a first dose of IS 5-MN (p<0.05). Time to 1 mm of ST depression increased significantly (p<0.05) and peak exercise ST segment depression decreased significantly (p<0.05). Time to onset of pain, rest and peak exercise heart rate, rest and peak exercise systolic blood pressure, peak double product did not change significantly. After 10 days of therapy the beneficial effects of IS 5-MN on exercise time and exercise time variables were not sustained. These data suggest that there is an attenuation of effect with respect to exercise time and ST segment variables. This may be a result of development of tolerance to IS 5-MN after 10 days of therapy.