Therapy and Prevention Pharmacology

The effects of oral diltiazem (360 mg/day) on exercise tolerance, left ventricular performance, and plasma lactate and catecholamine levels were studied in 13 patients with atherosclerotic coronary artery disease in a placebo-controlled, randomized, double-blind protocol. Exercise duration to the onset of ischemic ST segment depression, time to angina pectoris, and time to peak exercise improved by 120, 174, and 144 sec, respectively (p < .0001). Left ventricular ejection fraction, as determined by radionuclide angiography, increased in patients at rest from 52 + 11% (mean + SD) during placebo therapy to 58 11% during diltiazem therapy (p < .001); at peak exercise ejection fraction increased from 44 11% during placebo treatment to 52 + 15% during diltiazem therapy (p < .01). The mean plasma norepinephrine level in patients at rest increased from 498 + 221 pg/ml during placebo treatment to 667 + 272 pg/ml during diltiazem therapy (p < .05). Resting standing blood pressure and supine and standing diastolic blood pressures decreased significantly with diltiazem. In all 10 patients followed over a long term, oral diltiazem caused persistent improvement in exercise performance at 12 to 20 weeks, without evidence of placebo effects. Thus, diltiazem is highly effective in divided doses of 360 mg/day for the therapy of chronic angina pectoris due to coronary artery disease. Circulation 68, No. 1, 139-147, 1983. DILTIAZEM HYDROCHLORIDE has been shown to be effective in the treatment of exertional angina pectoris in doses of 240 mg/day.1 Although divided doses of up to 360 mg/day have been useful in treating patients with variant angina,2'3 previously reported studies have not evaluated this dose for the long-term therapy of patients with exertional angina pectoris. Dose titration studies have shown that beneficial effects of diltiazem can be demonstrated by exercise treadmill testing in patients with coronary artery disease at doses From the Division of Cardiology, University ofTexas Health Science Center and Audie Murphy Veterans Administration Medical Center, San Antonio. Supported in part by a grant-in-aid from the American Heart Association, Texas Affiliate; the Veterans Administration; and NIH grant 5T32HL07350. Presented in part at the American Heart Association Scientific Sessions, November 15-18, 1982, Dallas, and American College of Cardiology Annual Scientific Sessions, April 25-29, 1982, Atlanta. Address for correspondence: Michael H. Crawford, M.D., Department of Medicine, University of Texas Health Sciences Center, 7703 Floyd Curl Dr., San Antonio, TX 78284. Received Jan. 4, 1983; revision accepted March 24, 1983. Vol. 68, No. 1, July 1983 of 240 mg/day, but not at lower doses."7 Single doses of 90 to 120 mg have also been demonstrated to be effective.8 9 Little data exist concerning the effects of higher doses of diltiazem (360 mg/day) on resting hemodynamics and left ventricular performance during exercise. Therefore, the purpose of this study was to evaluate the safety, efficacy, and hemodynamic effects of 360 mg/day diltiazem in divided doses for the treatment of chronic stable exertional angina pectoris. Materials and methods Patient selection. Thirteen patients between the ages of 49 and 70 years (mean 61.5) were included in the study group. Study patients were required to have had stable angina pectoris for at least 3 months, to have typical exertional chest pain relieved by nitroglycerin, and to have previous exercise treadmill test results positive for both chest pain and ischemic ST segment depression in an anterolateral precordial lead. Patients who had had a myocardial infarction in the preceding 6 months or had concurrent congestive heart failure, valvular heart disease, significant arrhythmias, or hypertension were excluded. Of the 13 patients who participated, 11 had previously documented myocardial infarctions. Of the 10 patients undergoing 139 by gest on A uust 7, 2017 http://ciajournals.org/ D ow nladed from