Author + information
- Received April 8, 1985
- Revision received June 18, 1985
- Accepted September 18, 1985
- Published online February 1, 1986.
- Dennis P. Humen, MD, FRCP(C)*,
- Pamela O'Brien, BScN,
- Paul Purves, BSc, RTNM,
- Donald Johnson, MD, FRCP(C) and
- William J. Kostuk, MD, FRCP(C), FACCa
- ↵aAddress for reprints: William J. Kostuk, MD, Cardiac Investigation Unit, University Hospital, Box 5339, Terminal A, London, Ontario, N6A 5A5 Canada.
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 betablockade 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 < 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 < 0.05 and 336 ± 76 seconds, p < 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. Cardiac index was higher at rest (3.2 ± 0.6 liters/min per m2) and during exercise (5.5 ± 1.2 liters/min per m2) with diltiazem therapy in relation to an increased heart rate (rest 66 ± 8 beats/min, exercise 95 ± 10).
Combination therapy of propranolol and diltiazem (particularly with the higher diltiazem dose of 360 mg/day) results in significant improvement in exercise capacity and reduction in symptoms without an increase in adverse effects or significant deterioration of left ventricular function in patients who have continued symptoms of angina on monotherapy alone.
↵* Present address: Division of Cardiology, University of Alberta, Hospital, Edmonton, Alberta, Canada.
This study was supported in part by The Ontario Heart and Stroke Foundation, Toronto, Ontario, Canada and Nordic Laboratories, Montreal, Quebec, Canada.
- Received April 8, 1985.
- Revision received June 18, 1985.
- Accepted September 18, 1985.
- American College of Cardiology Foundation