Cardiovascular adverse drug reaction associated with combined beta-adrenergic and calcium entry-blocking agents

Numerous studies have shown a beneficial effect of combination therapy with beta-blockers and calcium antagonists in patients with anginal syndrome an d/or hypertension. However, because both agents exert a negative chronotrop ic effect, their combined use may cause bradyarrhythmias with resultant sym ptoms of cerebral, coronary, and systemic hypoperfusion. We describe our cl inical experience with patients who had cardiovascular adverse drug reactio ns (CVADRs) with combination therapy. This prospective study included 26 pa tients who had CVADRs among 2,574 admissions during a 2-year period. The st udy group included 14 men and 12 women with a median age of 73 years. Vario us combinations of calcium antagonists and beta-blockers were associated wi th the CVADRs. The most frequent pharmacologic combination was diltiazem pl us propranolol. The CVADRs were the cause for hospital admission in 10 pati ents, an associated cause in nine patients, and developed during hospitaliz ation in seven patients. Cardiac bradyarrhythmias were found in 22 patients . These rhythm abnormalities resolved within 24 h after discontinuation of the offending drugs. Temporary transvenous pacemaker insertion was necessar y in only one patient with complete atrioventricular block. Twenty-two pati ents recovered, two patients died of pump failure not associated with CVADR s, and in two patients, the CVADRs contributed to the patients' death. CVAD Rs an not uncommon in elderly patients with ischemic heart disease and/ or hypertension treated with the concomitant use of calcium antagonist and bet a-adrenergic blocking drugs. Use of calcium antagonist plus beta-blocker ma y unpredictably cause serious hemodynamic events, marked suppression of sin us node activity, and prolongation of atrioventricular conduction in some p atients. Enhanced therapeutic monitoring may be warranted when calcium anta gonists are combined with beta-blockers.