The study, presented in the Late Breaking Clinical Trial Update Session yesterday, reports a new analysis 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. This unacceptably high event rate occurs despite widespread use of evidence based therapies.
Digoxin was approved in USA by Food and Drug Administration (FDA) in 1998 for HF. But since then, use of digoxin has declined dramatically. In the OPTIMIZE-HF registry (Am Heart J. 2004;148: 43-51), 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.
“The decrease in use is likely to be due to the fact that digoxin is an orphan drug which isn’t promoted by the pharmaceutical industry,” said Dr Mihai Gheorghiade, the lead author and presenter of the study.
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 show that the mean age of patients in the study was 64 years, that 26% of patients were female and 17% African-American. 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).
Again, the analysis showed that at two years, significantly less patients receiving digoxin experienced heart failure related mortality or heart failure related hospitalisation. 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).
“Right now, one of the most pressing problems we have in the United States is to reduce 30-day hospital re-admissions for HF. This study shows that digoxin is effective in reducing hospitalisation in patients with HF-REF who have severe signs and symptoms of HF,” said Gheorghiade, from the Centre of Cardiovascular Innovation at Northwestern University Feinberg School of Medicine in Chicago. These results however, he stressed, were obtained in patients not receiving beta blocker therapy or aldosterone blocking agents.
“The real significance is that digoxin is an inexpensive and relatively safe drug that’s already approved for use in HF and that should be considered in patients with sinus rhythm or AF and reduced EF when severe signs and symptoms persist after a hospitalisation for HF.”