Elfect of the addition of propranolol to therapy with nifedipine for unstable angina pectoris : a randomized , double-blind , placebo-controlled trial

The value of the addition of f8-blockers to coronary vasodilator therapy in the treatment of patients with unstable angina at rest is controversial. We conducted a double-blind, randomized, placebo-controlled 4 week trial of propranolol in 81 patients with unstable angina, 39 of whom were assigned to placebo and 42 ofwhom received propranolol in a dose of at least 160 mg daily. All patients were also treated with coronary vasodilators, including 80 mg nifedipine daily and long-acting nitrates. The incidences of cardiac death, myocardial infarction, and requirement for bypass surgery or coronary angioplasty did not differ between the two groups (propranolol = 16; placebo = 18). The propranolol group had a lower cumulative probability of experiencing recurrent resting angina than the placebo group (p = .0 13), and over the first 4 days of the trial the mean number of clinical episodes of angina (propranolol 0.9 + 0.2, placebo 1.8 ± 0.3, p = .036), duration of angina (propranolol 15.1 + 4.3 min, placebo 38.1 + 8.4, p = .014), and nitroglycerin requirement (propranolol 1.1 + 0.3 tablets, placebo 3.5 + 0.8, p = .003) were also fewer. Continuous electrocardiographic recording for ischemic ST segment changes revealed fewer daily ischemic episodes in the propranolol group (2.0 + 0.5) than in the placebo group (3.8 + 0.7, p = .03), and a shorter duration of ischemia (propranolol 43 + 10 min, placebo 104 + 28 min, p =.039). Thus propranolol, in patients with unstable angina, in the presence of nitrates and nifedipine is not detrimental and reduces the frequency and duration of symptomatic and silent ischemic episodes. Circulation 73, No. 2, 331-337, 1986. THE EFFICACY of /3-blockers in the treatment of patients with stable, demand-related angina has been demonstrated.'-' Their use is controversial, however, in patients with resting angina. Although the negative inotropic and chronotropic properties of fl-blockers are theoretically advantageous in the treatment of myocardial ischemia, the primary pathophysiologic event in From the Division of Cardiology, Department of Medicine, Francis Scott Key Medical Center and The Johns Hopkins Hospital, Baltimore. Dr. Gottlieb was supported in part by a Research Fellowship Award from the American Heart Association, Maryland Affiliate. Computational assistance was received from CLINFO, sponsored by a grant (5 MOl RR 35-20) from the National Institutes of Health. Address for correspondence: Sidney 0. Gottlieb, M.D., Director,  The Johns Hopkins Medical Institutions, 4940 Eastern Ave., Baltimore, MD 21224.  1985; revision accepted Nov. 7, 1985. Presented in part at the 57th Scientific Sessions of the American Heart Association, November 12-15, 1984, Miami Beach. Vol. 73, No. 2, February 1986 these patients is often a reduction in coronary flow caused by coronary vasoconstriction and/or platelet aggregation.45 Vasoconstriction is known to occur in atherosclerotic portions of coronary arteries,65 and to be potentiated by fl-blockade.6 W" Coronary vasodilator therapy, consisting of nitrates and often nifedipine, is generally used in the therapy of resting anginal2'and these drugs may prevent the potential undesirable effects of fl-blockade. Conversely, treatment with vasodilators alone may in some instances produce a significant reflex sympathetic tachycardia that may increase myocardial oxygen demand and therefore be detrimental in patients with high-grade coronary artery stenoses.16 Thus, patients with fixed atherosclerotic coronary disease and resting angina in whom coronary spasm may be superimposed on obstructive lesions may benefit from the anti-ischemic effects of 331 by gest on A ril 0, 2017 http://ciajournals.org/ D ow nladed from