THERAPY AND PREVENTION Beneficial effects of timolol on infarct size and late ventricular tachycardia in patients with acute myocardial infarction

This investigation was undertaken to study the effects of 8-adrenergic blockade with timolol on infarct size and on the incidence of late ventricular tachycardia in patients with acute myocardial infarction of less than 6 hr of evolution. Patients were assigned randomly either to a placebo-treated group (98 patients) or to a timolol-treated group (102 patients). The patients were treated with 5.5 mg iv timolol (or matched placebo) as a bolus divided into four doses during the first 2 hr followed by 10 mg orally twice daily for 1 month. Cumulative total creatine kinase (CK) release, which reflects the amount of myocardial necrosis was 1677 + 132 IU/liter in the placebo group (n = 83) and 1274 + 73 IU/liter in the timolol group (n = 81, p<.01), a 24% reduction. Cumulative release ofCK-MB was 138 + 8 IU/liter in the placebo group and 106 + 8 IU/liter in the timolol group (p< .01), a 23% reduction. Twenty-four hour Holter electrocardiograms were obtained on days 7, 14, 21, and 28 after the onset of the acute myocardial infarction in 80 patients in the placebo group and 82 patients in the timolol group. The incidence of ventricular tachycardia was lower in the timolol than in the placebo group (7 vs 16 patients, p .05). We conclude that early administration of intravenous timolol followed by oral treatment in patients with acute myocardial infarction reduces infarct size as assessed by CK and CK-MB serum activity, and decreases the occurrence of late ventricular tachycardia. Circulation 76, No. 3, 610-617, 1987. THE PROGNOSIS of patients with acute myocardial infarction is related to the extent of the infarcted zone, 1 2to the occurrence of serious late ventricular arrhythmias ,3-6 and to the recurrence of myocardial ischemia. 8 Experimental studies have shown that ,3-adrenergic blockade reduces myocardial ischemic damage when administered early after coronary artery occlusion.9-14 Initial clinical studies that examined the effects of /3adrenergic-blocking agents on myocardial damage showed promising results.to 15 16 Results of subsequent investigations, however, were conflicting. Some of these investigations have been criticized because of the lack of an adequate control group,16 the small Supported by a grant from Merck Sharp and Dohme Argentina. Address for correspondence: Fernando Roque, M.D._ Departamento de Enfermedades Cardiovasculares, Clinica Olivos, Arenales 1525 Vicente Lopez (1602), Buenos Aires, Argentina. Received Jan. 5, 1987; revision accepted April 30, 1987. *Participating institutions and investigators are listed before the references. 610 number of patients studied,15 17 or because of the relative delay in starting treatment. 18 Recently, timolol was shown to decrease myocardial infarct size as judged by enzymatic and vectorcardiographic