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The effects on curdiac function of captopril (CPT) and digoxin (D) were compared in a study of 16 patients with chronic heart failure due to ischemic heart disease (15) and to congestive cardiomyopathy (I) (New York Heart Association class II n.13 and class III n.3). All patients were normotensive and in sinus rhythm. CPT 25 mg every 8 hours (t.i.d.) or D 0.25 mg once daily was given in a single-blind crossover design: A placebo (PLC) t.i.d. was given for 5 to 10 days, then CPT or D. according to a random sequence, replaced three or one of the PLC tablets; after one month, CPT and D were switched to PLC for 5 to 10 days; subsequently, the PLC tablets were replaced by CPT in the patients who previously received D and vice versa, and both treatments were again continued for one month. PLC. CPT. and D tablets were all identical. Diuretics once daily were given throughout the study. Plasma renin activity (PRA). plasma aldosterone (ALDO). plasma noradrenaline (NA). and adrenaline (A) were determined at the end of the two PLC periods and the two active treatments. A hand grip and a bicycle exercise were performed at the end of the two PLC periods and the two active treatments. No difference was noted between the PLC periods. PRA increased with CPT and did not change with D. ALDO was decreased by both CPT and D. NA and A were similarly decreased by both drugs, both supine and standing. Cardiac function (evaluated by systolic time intervals) and exercise tolerance (evaluated by exercise duration, total work performed, oxygen consumption, and ventilation) were improved by both drugs. The blood pressure was lower during CPT than D treatment (P<0.05). but no other difference was noted when CPT and D were compared. No side effects were noted with cither drug. Therefore. CPT with its lower toxicity and wider therapeutic range might be considered as an alternative to D in patients in sinus rhythm with chronic heart failure. NYHA functional class II-III.