Digoxin and increased mortality among patients recovering from acute myocardial infarction: importance of digoxin dose. The SPRINT Study Group.

Digoxin therapy has been suggested to increase mortality risk in survivors of acute myocardial infarction. Since digoxin is a drug with a narrow therapeutic/toxic ratio, we raised the hypothesis that the association between digoxin and post myocardial infarction mortality may have a dose-dependent relationship. The purpose of this study was to evaluate this hypothesis. We retrospectively analyzed data from 1731 survivors of acute myocardial infarction. At the time of hospital discharge, 175 patients (10%) were taking digoxin. The exact dosage of digoxin was ascertained in 153 (87%) patients. Patients were divided into two groups based on the weekly dosage of digoxin at hospital discharge: The first group included 41 patients who were treated with a low dose (< or = 1.5 mg per week, usually 0.125 mg daily). The second group included 112 patients treated with a full dose (> 1.5 mg per week, usually 0.25 mg daily). Both groups were comparable with regard to mean age, gender, history of prior myocardial infarction, diabetes mellitus, hypertension, and prior angina. There were no significant differences in the incidence of in-hospital complications, such as heart failure, atrial fibrillation, ventricular tachycardia, ventricular fibrillation, and postinfarction angina. One year mortality was significantly higher among patients treated with a full dose [19 of 112 (17%)] than patients treated with a low dose of digoxin [1 of 41 (2%); p < 0.02] Multivariate analysis performed by the Cox proportional hazards model identified treatment with a full dose of digoxin as an independent determinant associated with increased death during the first year after myocardial infarction (hazard ratio 10.7; 95% confidence interval 1.4-80.5). Thus, mortality among myocardial infarction survivors treated with digoxin was related to a full-dose therapy. Patients treated with a low dose experienced a low mortality rate. Our findings raise concern that digoxin may exert a dose-dependent deleterious effect upon the survival of patients recovering from acute myocardial infarction.