Efficacy of isosorbide mononitrate in angina pectoris

• Published in: The American journal of cardiology Vol. 70; no. 17; pp. 67G - 71G
• Main Authors: Thadani, U, de Vane, P J
• Format: Journal Article
• Language: English
• Published: United States 27.11.1992
• Subjects: Angina Pectoris - drug therapy; Clinical Trials as Topic; Drug Administration Schedule; Drug Tolerance; Humans; Isosorbide Dinitrate - administration & dosage; Isosorbide Dinitrate - analogs & derivatives; Isosorbide Dinitrate - therapeutic use; Vasodilator Agents - administration & dosage; Vasodilator Agents - therapeutic use
• ISSN: 0002-9149
• DOI: 10.1016/0002-9149(92)90029-X

The rapid development of tolerance has limited the applicability of oral and transdermal nitrates in the long-term management of patients with chronic stable angina pectoris. Recent well-controlled trials have demonstrated that asymmetrical, or eccentric, dosing of oral isosorbide mononitrate, in which 20-mg doses are taken at 8 A.M. and 3 P.M., provides at least 12 hours of antianginal coverage. There is no evidence for the development of tolerance with this schedule, which allows for a 17-hour nitrate withdrawal period. Likewise, the asymmetrical 20-mg twice daily regimen has not been associated with the zero-hour effect that has been reported with higher oral doses of isosorbide mononitrate and with intermittent nitroglycerin patch therapy. This approach also avoids the development of a clinical rebound phenomenon, as measured by increased episodes of angina and nitroglycerin consumption, compared with the pretreatment period, during the nitrate-free interval at night and the early hours of the morning.