Benefits of Short- and Long-Term, Maximally Tolerated Diltiazem Therapy for Chronic Effort Angina in Patients Receiving Long-Term Nitrates

Abstract

The safety and efficacy of maximally tolerated doses of oral diltiazem were evaluated in both short-term (Phase I, 14 weeks) and long-term (Phase II, 46 weeks) periods in 15 patients with chronic, stable effort angina who were taking long-acting nitrates throughout the study. Both phases were designed to compare the effects of diltiazem against placebo in a double-blind, crossover fashion. Thirteen of the 15 patients tolerated the maximum diltiazem dosage (360 mg/day). No patient had intolerable aggravation of angina after an abrupt discontinuation of diltiazem encountered in the double-blind segments. Serial treadmill testing documented the increase in time to onset of angina, time to appearance of 1-mm ST segment change, and total exercise duration in both double-blind phases with diltiazem plus nitrate compared with placebo plus nitrate (P <.05). Mean ST segment change was significantly reduced, especially during the chronic (Phase II) diltiazem plus nitrate evaluation, as was the heart rate-systolic pressure double product (attributed to lowered heart rates). The number of patients completing the treadmill without angina increased from baseline (20%) to Phase I (60%) and again at Phase II (87%). This study documents the value of high-dose diltiazem when added to maximally tolerated oral nitrates in reducing angina and improving treadmill performance as shown by reduced rate pressure products in the face of increased levels of external work.