Hemodynamic and antiischemic effects of intravenous elgodipine, a new dihydropyridine calcium channel blocker, in patients with chronic stable angina

Abstract

Elgodipine is a new second-generation dihydropyridine calcium antagonist. Its hemodynamic and antiischemic properties were evaluated in a single-blind, placebo-controlled trial in 22 males with chronic stable angina. Coronary artery disease was angiographically confirmed. Measurements were performed with a Swan-Ganz thermodilution catheter during a 30-minute period of rest and before the end of a 4-minute bicycle exercise test at maximum individual workload, both with placebo (IV infusion of 5 ml saline over 30 minutes) and elgodipine (10 micrograms/kg/2 min bolus IV, then IV infusion of 1 micrograms/kg/min for 28 minutes. Elgodipine caused very similar hemodynamic changes at rest and during exercise. Its major hemodynamic modification was the marked decrease in systemic vascular resistance, which was accompanied by an increase in cardiac index and stroke volume. Mean arterial blood pressure was slightly reduced, whereas the opposite small increase in heart rate meant that the double product remained unchanged. Contrary to resting conditions, pulmonary capillary wedge pressure, pulmonary artery pressures, pulmonary vascular resistance, and mean right atrial pressure remained normal or increased to a lesser extent during exercise after elgodipine. After elgodipine ischemic ST depression during exercise was diminished, and 11 of 16 assessable patients remained free from angina pectoris. We conclude that elgodipine is an efficacious antianginal drug. Its major mechanism of action is lowering of systemic vascular resistance. Thus elgodipine improves systolic cardiac function in patients with chronic stable angina and may delay the onset of ischemic diastolic dysfunction during exercise, as indicated by a normal left ventricular end-diastolic pressure (LVEDP). The data also suggest an improvement in coronary blood flow during exercise.

Hemodynamic effects of intravenous elgodipine in coronary artery disease during rest and exercise, and basic pharmacokinetic parameters

“…In another study, a total dose of 38 ~g/kg iv elgodipine over 30 minutes produced a significant decrease in resting DBP but not in SBP [5], which was similar to our results with the bolus (20 ~g/kg). Exercise RPP was not influenced after infusion of 38 ~g/kg [5] but was significantly decreased after 64 ~g/kg in this study.…”

“…In another study, a total dose of 38 ~g/kg iv elgodipine over 30 minutes produced a significant decrease in resting DBP but not in SBP [5], which was similar to our results with the bolus (20 ~g/kg). Exercise RPP was not influenced after infusion of 38 ~g/kg [5] but was significantly decreased after 64 ~g/kg in this study. The transient increase in rest HR and RPP indicates that the bolus (15 ~g/kg/2 min) may have produced higher elgodipine concentrations for a short period of time and may, therefore, be regarded as a threshold to an overdose.…”

“…L17-0691) solution were provided by Laboratorios Delagrange/Instituto de Investigacion y Desarollo Quimico Biologico, Alcobendas, Madrid, Spain. Drug administration was performed in singleblind manner with perfusion pumps, with the same design as used by Kuhn et al [5]. Following recovery from the control exercise, 50 ml placebo infusion was given over 30 minutes.…”

“…Nisoldipine (8 ~g/kg iv) attenuated exercise-induced angina pectoris in 8 of 16 patients, but a worsening was observed in 2 patients [20]. Elgodipine (60 mg oral) [4], 38 ~g/kg iv [5] or 64 ~g/kg iv) decreased the incidence cf exercise-induced angina pectoris by half and thus seems to be of comparable clinical efficacy.…”

“…Intravenous elgodipine (38 ~g/kg) reduced systemic vascular resistance and increased cardiac index and stroke volume both at rest and at peak supine exercise. Pulmonary capillary wedge pressure, mean pulmonary artery pressure, and mean right atrial pressure were increased at rest but were decreased at peak exercise as compared with a control exercise [5]. However, the influence of elgodipine on hemodynamics during exercise, that is, during conditions of acute increase in myocardial oxygen demand, and basic pharmacokinetic parameters in patients have not been previously investigated.…”