Effectiveness and Safety of Digoxin among Contemporary Adults With Incident Systolic Heart Failure

This cohort study, which investigated 2891 patients with newly diagnosed systolic HF (18% received digoxin during the study), reported that incident digoxin use was associated with higher rates of death (14.2 vs. 11.3 per 100 person-years) but no difference in HF hospitalisation.

The NICE clinical guideline on chronic heart failure, 2010, recommends digoxin for worsening or severe heart failure due to left ventricular systolic dysfunction despite first- and second-line treatment for heart failure.

 

This cohort study identified patients who had not been previously exposed to digoxin. The authors used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalisation, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. They also conducted analyses stratified by sex and concurrent β-blocker use.

 

After a median follow-up period was 2.5 years, there were a total of 801 deaths (737 off digoxin and 64 on digoxin). The crude rate of death was significantly higher on digoxin therapy (14.2 per 100 person-years) than off digoxin therapy (11.3 per 100 person-years; P=0.04). After adjustment for potential confounders, current digoxin use was associated with a 72% higher relative rate of death (adjusted hazard ratio [HR], 1.72; 95% CI, 1.25–2.36). During follow-up, there were 1723 hospitalisations for HF overall (1596 off digoxin, 127 on digoxin). The crude rate of hospitalisation for HF was higher for patients receiving digoxin (28.2 per 100 person-years) compared with those off digoxin therapy (24.4 per 100 person-years; P=0.06). After adjustment for potential confounders, current digoxin use was not significantly associated with hospitalisation for HF (adjusted HR, 1.05; 95% CI, 0.82–1.34).

 

The authors highlighted the following limitations to the study:

• As an observational study of outcomes associated with a therapy, it is not possible to fully rule out the possibility of residual confounding. Digoxin is currently indicated in patients with systolic HF and persistent symptoms despite maximal medical therapy, and the study may not have completely eliminated confounding by indication.
• Even though the study was conducted within a large healthcare delivery system in northern California, the results may not be fully generalisable to other populations cared for in different settings.

 

The Digitalis Investigation Group (DIG) randomized trial showed that digoxin did not lower mortality among patients with systolic heart failure but did reduce hospitalisations for worsening heart failure.

 

The DIG trial enrolled highly selected patients between 1991 and 1993, before several substantial advances in heart failure therapy and a significant shift in the epidemiology of systolic heart failure toward more ischemic cardiomyopathy. The authors of this cohort study state that their findings suggest that the use of digoxin should be re-evaluated for the treatment of systolic HF in the modern era.