Increased exercise tolerance and reduced electrocardiographic ischemia with diltiazem in patients with stable angina pectoris.

Abstract

SUMMARY Diltiazem is a calcium slow-channel blocking drug that may be effective in the treatment of chronic stable angina pectoris. To evaluate the therapeutic efficacy 3 hours after a single oral dose of 120 mg, 12 men with chronic stable angina pectoris performed a maximal exercise test on a bicycle ergometer after ingesting either placebo or diltiazem administered in a double-blind fashion. During submaximal exercise at a fixed work load, diltiazem decreased the average heart rate response from 119 ± 17 to 107 ± 14 beats/ min (p < 0.01), systolic blood pressure from 182 ± 15 to 175 ± 15 mm Hg (p < 0.05) and the rate-pressure product from 21.8 ± 4.2 to 18.8 ± 3.2 x 10-3 units (p < 0.01). The average submaximal work load at which significant ST-segment depression (0.1 mV) first appeared was increased from 355 ± 142 to 525 + 143 seconds (p < 0.01) after diltiazem. At peak exercise after diltiazem, the average depth of ST-segment depression in any one lead and the extent of myocardial ischemia observed in all 12 ECG leads were decreased (p < 0.01), even though the average work load was increased by 29% (p < 0.01). Peak heart rate, systolic blood pressure and rate-pressure product were similar with placebo and diltiazem. The plasma diltiazem concentration was 139 ± 29 ng/ml 3 hours after ingestion and was significantly (p < 0.05) related to the increased time to the onset of important ST-segment depression (r = 0.65) and to the decrease in the extent of myocardial ischemia observed in all 12 ECG leads (r = -0.61) compared with placebo. Thus, diltiazem is effective in treating chronic stable angina pectoris. It decreases myocardial oxygen requirements during upright exercise and appears to increase myocardial oxygen delivery.THE EFFECTIVENESS of diltiazem, a calcium slowchannel blocking drug, in the prevention of coronary spasm is well documented.' It decreases systemic arteriolar resistance, increases coronary artery blood flow and has a negative chronotropic effect.t fThese properties have justified its study in the treatment of exertional angina in patients with fixed coronary artery stenoses.]-1' Repeat oral-dose studies of diltiazem show an increase in the time to the onset of angina or to significant ST-segment depression during standard multistage exercise testing.7-9 Both the total daily dose and schedule appear to influence the drug's efficacy and ability to reduce indexes of myocardial oxygen demand during exercise. Hossack and Bruce7 found a greater effect using 60 mg four times daily than smaller doses and with a schedule of 30 mg four times daily vs 60 mg three times daily. Single-dose studies'0 " with 60 and 90 mg of diltiazem have not shown a significant decrease in the indexes of myocardial oxygen demand during exercise.Therefore, in the present study, we compared, after 3 hours, the effects of a single oral dose of 120 mg of diltiazem vs placebo on the time to the onset of significant ST-segment depression (0.1 mV) and to peak exercise; the indexes of myocardial oxygen consumption at a fixed submax...

The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

“…On propranolol alone the mean plasma propranolol concentration was 118 ng/ml (range 64 to 183) and in combination with diltiazem it was 109 ng/ml (range 23 to 180 THERAPY AND PREVENTION-CORONARY ARTERY DISEASE ment in exercise capacity with an increase in dose levels from 120 mg to 240 mg/day. Single-dose studies in which as much as 120 mg diltiazem was used15 16 have shown no associated significant adverse effects. Consequently, we wanted to examine the short-term safety and efficacy of high-dose diltiazem (90 mg four times daily) in patients with stable effort angina.…”

Effects of nicardipine on coronary blood flow, left ventricular inotropic state and myocardial metabolism in patients with angina pectoris.

“…Although calcium antagonists are now universally only in chemical structure but also in terms of recognized as major therapeutic agents in their negative inotropic effects or their effects on ischaemic heart disease (Hugenholtz et al, 1981; myocardial relaxation, coronary blood flow, and Gunther et al, 1981;Zacca et al, 1982;Rouleau oxygen consumption (Rousseau et al, 1980(Rousseau et al, , et al, 1983Wagniart et al, 1982;Braunwald, 1981;Walsh & O'Rourke, 1983;Gelpi et al, 1983), the pharmacologic profile of the ideal 1983; Rouleau et al, 1983; Emanuelsson & calcium antagonist to treat angina pectoris Holmberg, 1983;Krebs, 1984). remains ill defined.…”

Short- and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: a placebo-controlled, randomized, double-blind crossover study.

“…Dose titration studies have shown that beneficial effects of diltiazem can be demonstrated by exercise treadmill testing in patients with coronary artery disease at doses of 240 mg/day, but not at lower doses. "7 Single doses of 90 to 120 mg have also been demonstrated to be effective.8 9 Little data exist concerning the effects of higher doses of diltiazem (360 mg/day) on resting hemodynamics and left ventricular performance during exercise. Therefore, the purpose of this study was to evaluate the safety, efficacy, and hemodynamic effects of 360 mg/day diltiazem in divided doses for the treatment of chronic stable exertional angina pectoris.…”