Clinical response and effects on left ventricular function of isosorbide dinitrate added to propranolol or diltiazem monotherapy in patients with chronic stable angina

Twenty-four patients were randomized to a double-blind, triple placebo controlled, latin square protocol to examine the relative efficacy of propranolol or diltiazem given as monotherapy or in combination with isosorbide dinitrate. Treatment phases were preceded and followed by placebo control periods. At the end of each phase, symptom-limited treadmill exercise stress tests were performed, as well as rest and exercise radionuclide ventriculography. Both forms of monotherapy were effective in reducing episodes of angina and nitroglycerin use, and in improving exercise tolerance. Diltiazem monotherapy was associated with slightly higher treadmill times (509.9 +/- 123 s) compared to propranolol (462.7 +/- 131 s, P less than 0.05). The addition of isosorbide dinitrate to either form of monotherapy allowed no further improvement in any of the measured clinical responses. Radionuclide ventriculography showed no significant difference in resting left ventricular function. The addition of isosorbide dinitrate to propranolol showed a reduction in end diastolic volume in keeping with a reduction in preload. In response to exercise, stress-induced left ventricular dysfunction was equal in all groups except for the diltiazem-nitrate combination, which was associated with a higher ejection fraction (56.2 +/- 8.6%) compared to monotherapy (52.6 +/- 10.9%, P less than 0.01). A higher cardiac output could be achieved in the groups treated with diltiazem; this was related to increased heart rate and maintenance of stroke volume. It was concluded that diltiazem is equally effective as propranolol for the treatment of chronic stable angina and, in terms of exercise capacity and cardiac output, superior to beta-blockade. The addition of isosorbide dinitrate appears to impart no overt benefits, but some evidence suggests a reduction in left ventricular decompensation in the face of stress.