Diltiazem and propranolol in combination: hemodynamic effects following acute intravenous administration

Diltiazem and propranolol are independently useful antianginal agents with common negative chronotropic, dromotropic, and inotropic properties. Concern over the safety of the concurrent use of these two drugs led to an investigation of their intravenous combination in 19 patients with suspected coronary artery disease. Hemodynamics were recorded in both a sinus and atrial paced rhythms at baseline and again following administration of a loading dose of diltiazem (0.25 mg/kg) followed by continuous infusion (0.002 mg/kg/min). Propranolol was then added by intravenous bolus (0.07 mg/kg) and continuous infusion (0.0012 mg/kg/min), with reassessment of hemodynamics once steady state was achieved. Patients were stratified by left ventricular ejection fraction (LVEF): group 1 (LVEF = 62% to 69%), group 2 (LVEF = 49% to 59%), and group 3 (LVEF = 20% to 47%). The combination of drugs resulted in a 15% drop in heart rate (p less than 0.01) and a 15% prolongation in the PR interval (p less than 0.01) for the group of 19 patients. Left ventricular end-diastolic pressure (LVEDP) was not significantly changed by diltiazem or its combination except in group 3. Cardiac output was lowered in all groups following diltiazem and propranolol (p less than 0.05). Untoward reactions included marked vasovagal reactions at the conclusion of the procedure in six patients. The combination of drugs resulted in profound sinus bradycardia with attendant 2:1 atrioventricular (AV) block in one patient. Diltiazem and propranolol were hemodynamically well tolerated in patients with preserved left ventricular function. Because of the additive negative dromotropic activities of these two drugs, ECG monitoring is warranted when they are acutely combined.