Digoxin - the oldest compound in cardiovascular medicine - has an important role to play in treating high risk patients with heart failure (HF), according to the latest analysis from National Health Blood and Lung Institute Digitalis Investigation Group (DIG) trial.
This analysis was conducted specifically in patients with NYHA class III-IV, left ventricular ejection fractions (LVEF) less than 25% and cardio thoracic ratios (CTRs) less than 50%.
Hospitalisation for HF is associated with post discharge mortality and re-admission rates that can be as high as 15 and 30% respectively at 60 to 90 days post discharge, despite the widespread use of evidence based therapies.
Digoxin was approved in USA by Food and Drug Administration (FDA) in 1998 for HF. But it is not commonly used in practice. In 2004, the OPTIMIZE-HF registry showed that only 30% of patients with HF and reduced EF (HF-REF) were treated with digoxin prior to admission. Furthermore, digoxin was added to only 8% of patients prior to discharge.
In the original DIG trial published in 1997 in New England of Medicine, 6,800 patients with HF-REF (LVEF <45%) and normal sinus rhythm were randomised to receive digoxin or placebo in addition to diuretics and ACE inhibitors. Results showed that while digoxin did not have an effect on mortality, it significantly reduced the rate of hospitalisation due to worsening HF.
In the current analysis, data for the 4,367 patients in the original analysis who met criteria for one of three high risk conditions was considered. The high risk characteristics, which were analysed separately, were NYHA III-IV, LVEF <25% or cardiothoracic ratio > 55%.
Results at 24 months show that for all-cause mortality or all-cause hospitalisation, patients randomised to digoxin did significantly better than those randomised to placebo. For NYHA class III-IV the HR was 0.88 (P=0.012); for LVEF < 25% the HR was 0.84 (p=0.001); and for those with CTRs >55% the HR was 0.85 (p=0.002).
Furthermore, the analysis showed that at two years, significantly less patients receiving digoxin experienced heart failure related mortality or heart failure related hospitalization. For NYHA class III to IV the HR was 0.65 (P<0.001); for LVEF < 25% the HR was 0.61 (p<0.001) and for CTRs > 55% the HR was 0.65 (p<0.001).
In conclusion, this trial demonstrated clinical benefits of digoxin in heart failure patients with NYHA III-IV, LVEF <25% or cardiothoracic ratio > 55%.