WITHDRAWAL OF DIGOXIN FROM PATIENTS WITH CHRONIC HEART-FAILURE TREATED WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

Background. Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is n ot clear whether the drug has a role when patients are receiving angio tensin-converting-enzyme inhibitors, as is often the case in current p ractice. Methods. We studied 178 patients with New York Heart Associat ion class 11 or Ill heart failure and left ventricular ejection fracti ons of 35 percent or less in normal sinus rhythm who were clinically s table while receiving digoxin, diuretics, and an angiotensin-convertin g-enzyme inhibitor (captopril or enalapril). The patients were randoml y assigned in a double-blind fashion either to continue receiving digo xin (85 patients) or to be switched to placebo (93 patients) for 12 we eks. Otherwise, their medical therapy for heart failure was not change d. Results. Worsening heart failure necessitating withdrawal from the study developed in 23 patients switched to placebo, but in only 4 pati ents who continued to receive digoxin (P<0.001). The relative risk of worsening heart failure in the placebo group as compared with the digo xin group was 5.9 (95 percent confidence interval, 2.1 to 17.2). All m easures of functional capacity deteriorated in the patients receiving placebo as compared with those continuing to receive digoxin (P = 0.03 3 for maximal exercise tolerance, P = 0.01 for submaximal exercise end urance, and P = 0.019 for New York Heart Association class). In additi on, the patients switched from digoxin to placebo had lower quality-of -life scores (P = 0.04), decreased ejection fractions (P = 0.001), and increases in heart rate (P = 0.001) and body weight (P<0.001). Conclu sions. These findings indicate that the withdrawal of digoxin carries considerable risks for patients with chronic heart failure and impaire d systolic function who have remained clinically stable while receivin g digoxin and angiotensin-converting-enzyme inhibitors.