Using Digitoxin to Manage Heart Failure Cases with Reduced Ejection Fraction
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on October 15th, 2025
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Cardiac glycosides such as digoxin are frequently prescribed to manage heart failure. However, previous studies have found digoxin to have limited effectiveness in managing heart failure with reduced ejection fraction. Due to recent advancement in other cardiovascular therapy, the German government has sponsored a study to examine the usage of digitoxin to manage heart failure with reduced ejection fraction.
The trial enrolled 1,212 patients with chronic heart failure and left ventricular ejection fraction below 40%. The average age was 66 years. Most participants (66%) were classified as NYHA III, experiencing symptoms with less than ordinary activity. While 30% were NYHA II and 4% NYHA IV. Half of the cases were ischemic in origin. Device therapy was common, with 65% receiving implantable cardioverter–defibrillators and 25% cardiac resynchronization therapy. Standard medications included beta-blockers (95%) and mineralocorticoid receptor antagonists (76%), followed by angiotensin receptor–neprilysin inhibitors (40%) and ACE inhibitors (36%). Fewer than 20% used angiotensin-receptor blockers or SGLT2 inhibitors, and only about 1% were on a cardiac glycoside at baseline.
Patients were randomized to receive either placebo or oral digitoxin starting at 0.07 mg daily, titrated between 0.05 and 0.1 mg to maintain serum concentrations of 8–18 ng/mL. Digitoxin, unlike digoxin, offers superior gastrointestinal absorption, higher protein binding, and elimination via enterohepatic excretion, reducing renal burden. After a median follow-up of 36 months, digitoxin reduced the composite risk of death or hospitalization by 18%. Subgroup analysis suggested the greatest benefit among patients with BMI <30, without hypertension, and without implanted cardiac devices. Concomitant use of other heart failure medications did not appear to enhance digitoxin’s effect.
The trial enrolled 1,212 patients with chronic heart failure and left ventricular ejection fraction below 40%. The average age was 66 years. Most participants (66%) were classified as NYHA III, experiencing symptoms with less than ordinary activity. While 30% were NYHA II and 4% NYHA IV. Half of the cases were ischemic in origin. Device therapy was common, with 65% receiving implantable cardioverter–defibrillators and 25% cardiac resynchronization therapy. Standard medications included beta-blockers (95%) and mineralocorticoid receptor antagonists (76%), followed by angiotensin receptor–neprilysin inhibitors (40%) and ACE inhibitors (36%). Fewer than 20% used angiotensin-receptor blockers or SGLT2 inhibitors, and only about 1% were on a cardiac glycoside at baseline.
Patients were randomized to receive either placebo or oral digitoxin starting at 0.07 mg daily, titrated between 0.05 and 0.1 mg to maintain serum concentrations of 8–18 ng/mL. Digitoxin, unlike digoxin, offers superior gastrointestinal absorption, higher protein binding, and elimination via enterohepatic excretion, reducing renal burden. After a median follow-up of 36 months, digitoxin reduced the composite risk of death or hospitalization by 18%. Subgroup analysis suggested the greatest benefit among patients with BMI <30, without hypertension, and without implanted cardiac devices. Concomitant use of other heart failure medications did not appear to enhance digitoxin’s effect.