Hemodynamic consequences of combined beta-adrenergic and slow calcium channel blockade in man

The administration of verapamil to patients receiving β-adrenergic blocking drugs is reported to produce adverse circulatory reactions, but a systematic investigation of this potential drug interaction has not been performed in man. We administered 40-, 80- and 120-mg doses of verapamil orally to 15 patients with angina pectoris who were receiving high doses of propranolol or metoprolol. Verapamil produced dose-dependent decreases in cardiac performance: with 120 mg, cardiac index decreased by 0.38 l/min/m², stroke volume index decreased by 2.8 ml/beat/m² and heart rate decreased by 6 beats/min, associated with increases in pulmonary capillary wedge (2.2 mm Hg) and mean right atrial pressures (1.7 mm Hg) (all p <0.01); two patients had marked, but asymptomatic, hypotensive reactions. In contrast, repeat administration of 120-mg doses of verapamil 24-30 hours after withdrawal of β blockade produced no significant cardiodepressant effects despite significantly higher plasma levels of verapamil than during propranolol therapy (383.1 vs 205.1 ng/ml, p <0.01). In conclusion, verapamil produces significant negative inotropic and chronotropic effects in patients treated with β-adrenergic antagonists; combination therapy should therefore be used with caution in patients with angina pectoris.