Effort angina with adequate beta-receptor blockade: comparison with diltiazem alone and in combination

Calcium channel blockers and beta-receptor blockers improve symptoms of myocardial ischemia by potentially different mechanisms. Accordingly, combination therapy may entail additive benefits. Twenty-four patients with symptomatic stable effort angina despite full beta-blockade were randomized to a double-blind Latin square protocol in which they received propranolol in a dose producing full beta-receptor blockade, diltiazem, 240 mg/day, in divided doses and a combination of propranolol and diltiazem, 240 or 360 mg/day. Treadmill testing (Bruce protocol) was utilized to assess exercise tolerance, radionuclide ventriculography to assess left ventricular function and clinical follow-up to assess adverse effects and overall clinical response. Comparable treadmill exercise times were observed with monotherapy (344 +/- 83 seconds with propranolol and 341 +/- 87 seconds with diltiazem) and the lower dose combination (361 +/- 87 seconds). With propranolol and diltiazem, 360 mg/day, however, there was a significant increase in treadmill time (393 +/- 106 seconds; p less than 0.05). In five patients whose treadmill exercise was limited by angina on all therapies, there was a significant improvement in the time to onset of chest pain with both low dose and high dose combinations (311 +/- 71 seconds, p less than 0.05 and 336 +/- 76 seconds, p less than 0.01, respectively). Improved treadmill performance was supported by the clinical response, while an increase in adverse effects was not observed. Thirteen of 24 patients blindly selected the higher dose diltiazem combination as their optimal therapy. Left ventricular dilation was observed (by radionuclide ventriculography) in response to exercise in each phase of therapy; this was related to stress-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)