Sustained hemodynamic and antianginal effects of high dose oral isosorbide dinitrate

Small doses of oral nitrates are ineffective antianginal agents. However, large doses of oral nitrates individually titrated to produce long-acting hemodynamic effects may be effective antianginal agents in many patients. The dose of nitrate prescribed should be titrated by blood pressure and heart rate measurements, the presence of adverse side effects, and by exercise tolerance studies before and during treatment. We would strongly recommend gradual reduction rather than an abrupt discontinuation of chronic, high-dose nitrate therapy in patients with angina pectoris to avoid possible nitrate dependence withdrawal effects. We would also recommend that continuous nitrate antianginal prophylaxis not be used in patients with angina pectoris whose symptons are readily controlled with less intensive nitrate therapy used as needed. Partial hemodynamic tolerance develops after chronic use of high-dose oral isosorbide dinitrate but the antianginal efficacy of both sublingual nitroglycerin and of high doses of oral isosorbide dinitrate is unimpaired. Patients with congestive heart failure have also had clinical and hemodynamic improvement following chronic nitrate therapy.