Combined therapy with Ca-antagonists and beta-adrenergic receptor blocking agents in chronic stable angina

There have been conflicting reports on the safety of combining beta-adrenergic receptor blockers and Ca++-antagonists, especially verapamil, in the treatment of cardiovascular diseases. Warnings have been raised against additive negative chronotropic and inotropic effects. This study was designed to compare the efficacy and safety of simultaneous administration of verapamil, 360 mg daily, and atenolol, 100 mg daily, with that of either drug alone. Eighteen patients (mean age 58 years) with chronic stable angina were included in the study. After a two-week run-in period, the patients received either drug alone for six weeks and were then given the combination for another six weeks. Frequent ECG and blood pressure measurements were performed. Radionuclide evaluation of left ventricular ejection fraction was done before and at the end of the combined therapy. Exercise testing using a bicycle ergometer was performed during each treatment period. Only one patient developed sinus bradycardia when on combined therapy (48 bpm). The P-Q time increased with single drug therapy as well as with the combination (p less than 0.01). Maximal exercise time increased more with the combination than with single drug therapy. No serious adverse hemodynamic effects were recorded. LVEF increased by 4.6% (p less than 0.01) with the combined therapy. A decrease in nitroglycerine consumption occurred, beeing most pronounced with the combined therapy and corresponding to a subjective improvement. It is concluded that an additive negative chronotropism occurred but that the combination is safe and offers an effective therapeutic alternative in chronic stable angina.