Coronary artery disease.

With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebocontrolled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (1 18 ± 28 mm Hg/min) was significantly greater (p < .05) than that by propranolol (135 + 27 mm Hg/min) or verapamil alone (163 ± 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased (p < .05) cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exerciseinduced hypokinesis (placebo 52 ± 20%, combination 61 + 23%; p < .01). No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil. Compared with single-drug therapy, the combination causes no further change in LV function of resting subjects and improves exercise function. This improvement was most likely due to a reduction in myocardial oxygen demand. Circulation 68, No. 6, 1280-1289, 1983. COMBINATION THERAPY with /8-adrenergic-receptor antagonists and nitrates is a well-established part of the treatment of chronic exertional angina. Recently, reports have shown that calcium-channel antagonists such as verapamil have antianginal properties comparable to those of propranolol.'-1 Moreover, in selected patients, the combination of propranolol and From the Cardiac Investigation Unit, University Hospital, and the Department of Medicine, University of Western Ontario, London, Ontario. Supported by the Ontario Heart Foundation. Address for correspondence: Dr. W. J. Kostuk, Cardiac Investigation Unit, University Hospital, Box 5339, Terminal A, London, Ontario, Canada N6A 5A5. Received April 15, 1983; revision accepted Sept. 1, 1983. 1280 verapamil may provide an antianginal effect superior to either drug alone.4' 9 10 The antianginal properties of propranolol differ in some respects from those of verapamil, providing a rationale for the use of combined therapy. Propranolol reduces the heart rate and blood pressure response both in patients at rest and during maximal exercise, thus decreasing myocardial oxygen demand. While verapamil reduces heart rate and blood pressure during submaximal exercise,4 the rate-pressure product at maximal exercise is usually similar or only slightly lower than that observed during the control period.' Despite this finding, clinical improvement with a reduction in the incidence of angina is often evident at maximal exercise, suggesting that verCIRCULATION by gest on N ovem er 2, 2017 http://ciajournals.org/ D ow nladed from THERAPY AND PREVENTION-CORONARY ARTERY DISEASE apamil has another mechanism of action that is responsible for its beneficial effect in patients with exertional angina. Both a coronary artery vasodilatory action" and improvement in diastolic filling properties have been suggested.'2 Unfortunately, since both drugs exert significant negative inotropic and chronotropic effects, concern has arisen regarding the adverse effects of fl-blockade and calcium-antagonist combination