New Trial Shows Benefit Of Digitoxin In Patients With Severe Heart Failure Symptoms

Digitoxin reduced nan consequence of a composite of all-cause decease and hospitalization for worsening bosom nonaccomplishment (HF) among patients pinch precocious HF and a reduced ejection fraction (HFrEF), according to a late-breaking proceedings presented successful a Hot Line convention coming astatine ESC Congress 2025.

Explaining nan rationale, Principal Investigator, Professor Udo Bavendiek from Hannover Medical School, Germany, said: "Cardiac glycosides, specified arsenic digitoxin and digoxin person been utilized to dainty bosom nonaccomplishment for 2 centuries. However, grounds for their beneficial effects successful HFrEF comes chiefly from a azygous randomised trial, nan DIG proceedings published successful 1997. Digoxin had an wide neutral effect connected nan superior endpoint of mortality successful nan DIG trial; however, little serum digoxin levels seemed to beryllium associated pinch improvements, while higher digoxin levels worsened prognosis. Notably, hospitalizations for worsening HF, a prespecified secondary outcome, were reduced pinch digoxin and nan top benefits were seen successful patients pinch pronounced HF symptoms and markedly reduced near ventricular ejection fraction (LVEF). We designed nan DIGIT-HF proceedings pinch digitoxin - which has unchangeable humor concentrations moreover successful patients pinch renal dysfunction - and included patients pinch HF and a pronounced HF denotation burden."

DIGIT-HF was a double-blind, placebo-controlled randomized proceedings conducted astatine 55 sites successful Germany, Austria and Serbia. Patients were eligible for inclusion if they had symptomatic HFrEF: NYHA functional people II and a LVEF of ≤30% aliases NYHA people III-IV and LVEF ≤40%. Patients were randomised 1:1 to digitoxin aliases placebo connected apical of standard-care treatment. Patients successful nan digitoxin group initially received 0.07 mg erstwhile regular pinch double-blind dose accommodation to 0.05 mg aliases 0.1 mg erstwhile regular aft 6 weeks to execute a digitoxin target attraction of 8-18 ng/ml. The superior result was a composite of all-cause decease and infirmary admittance for worsening HF (whichever occurred first), analysed according to nan intention-to-treat (ITT) principle.

The 1,212 patients successful nan ITT organization had a mean property of 66 years, pinch 20% being female. The mean LVEF was 29% and nan HF denotation load was precocious - 70% of patients had NYHA people III aliases IV. Contemporary pharmacological HF therapy was good implemented crossed nan population, including precocious uptake of defibrillator-based devices (64%; cardiac resynchronisation therapy 25%).

Over a median of 36 months, nan superior result occurred successful 39.5% of patients successful nan digitoxin group and 44.1% successful nan placebo group (hazard ratio [HR] 0.82; 95% assurance interval [CI] 0.69 to 0.98; p=0.03).

In total, 27.2% of patients successful nan digitoxin group and 29.5% successful nan placebo group died (HR 0.86; 95% CI 0.69 to 1.07). A first infirmary admittance for worsening HF occurred successful 28.1% of patients successful nan digitoxin group and 30.4% successful nan placebo group (HR 0.85; 95% CI 0.69 to 1.05). The full number of deaths from immoderate origin and hospitalizations for worsening HF was 537 successful nan digitoxin group and 531 successful nan placebo group (rate ratio 0.85; 95% CI 0.67 to 1.09).

The superior result appeared affirmative successful each pre-specified subgroups, but those pinch bosom complaint ≥75 bpm aliases systolic humor unit ≤120 mmHg appeared to beryllium associated pinch peculiar benefit. Regarding safety, superior adverse events occurred successful 4.7% of patients successful nan digitoxin group and 2.8% successful nan placebo group, predominantly cardiac disorders (3.4% and 1.8%, respectively).

Professor Bavendiek concluded: "We were capable to show that utilizing a elemental dose-titration protocol, digitoxin importantly reduced all-cause decease and hospitalization for worsening HF successful patients pinch well-implemented HF therapy, contempt lower-than-expected enrolment. Based connected our findings, digitoxin represents an further action for patients pinch HFrEF, peculiarly those pinch atrial fibrillation, higher bosom rates, debased humor unit aliases impaired kidney function."