Angina symptoms that are not resolved with beta-blocker therapy may be relieved with the addition of amlodipine or diltiazem. Diltiazem has a negative chronotropic effect that adds to its antianginal efficacy but may also result in symptomatic bradycardia and fatigue. Amlodipine has greater selectivity for vascular smooth muscle over nodal and contractile cardiac tissue, causing no change in the cardiac rate. Knight and associates compared the efficacy of amlodipine with that of diltiazem to supplement atenolol therapy in patients with stable angina pectoris.

A total of 97 patients participated in the randomized, double-blind parallel group study. Patients with positive stress tests on screening received atenolol, 50 mg per day, with sublingual glyceryl trinitrate as required. If a further exercise test performed after two to three weeks of therapy demonstrated results consistent with the initial test, the patient was included in the study and randomized to receive either amlodipine (5 mg once daily) with diltiazem placebo or diltiazem (90 mg twice daily) with amlodipine placebo. If angina was still present after four weeks, the dosage was doubled for an additional four weeks. Patients recorded onset and duration of angina attacks and glyceryl trinitrate use. Ambulatory ST–segment monitoring and exercise testing were completed after the double-blind treatment.

Both amlodipine and diltiazem significantly reduced the frequency of angina attacks and glyceryl trinitrate consumption. Both drugs reduced systolic blood pressure slightly, and neither affected the heart rate significantly. In both treatment groups, more than 60 percent of the patients progressed to the higher dosage of study medication. The incidence of adverse effects was higher in the group taking diltiazem, with severe adverse events including syncope, atrial fibrillation and bradycardia. The most serious adverse effect with amlodipine therapy was severe edema.

The authors conclude that both amlodipine and diltiazem provide an improvement in exercise parameters when added to a beta blocker in the treatment of patients with angina. Both drugs are well tolerated, although adverse events were more likely in the diltiazem group. The pattern of adverse events was also different, with an increased incidence of bradycardia in the diltiazem group.