Higher Digoxin Levels Associated With Increased Mortality In Men With Heart Failure/Left Ventricular Dysfunction

Higher serum digoxin concentrations (SDCs) have been associated with increased mortality in men with heart failure and left ventricular dysfunction, research from the United States indicates.

Investigators from Yale University in New Haven, Connecticut, and the University of Colorado Heath Sciences Centre in Denver say that the finding suggests the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimised in the SDC range of 0.5 nanograms per millilitre to 0.8 ng/mL.

“Our analyses suggest that previously accepted SDCs of 1.2 ng/mL and higher may be harmful and that currently recommended therapeutic SDCs of approximately 1.0 ng/mL may not provide any clinical benefit compared with placebo,” the researchers say.

The researchers did a post hoc analysis of the randomised, double-blind, placebo-controlled DIG trial conducted from August 1991 to December 1995.

Patients randomly assigned to digoxin were divided into three groups based on SDC at one month: 572 had levels of 0.5 ng/mL to 0.8 ng/mL, 322 had levels of 0.9 ng/mL to 1.1 ng/mL and 277 had levels of 1.2 ng/mL or higher. They were compared with 2,611 patients randomly assigned to receive placebo.

All-cause mortality at 37 months was the main outcome measure used.

Higher SDCs were associated with increased crude all-cause mortality rates, the researchers say. The rate for men in the 0.5 ng/mL-to-0.8 ng/mL group was 29.9%. It was 38.8% for those in the 0.9 ng/mL-to-1.1 ng/mL group and 48% for those in the 1.2 ng/mL or higher group.

Patients in the 0.5 ng/mL-to-0.8 ng/mL group had a 6.3% lower mortality rate compared with placebo patients. Patients in the 1.2 ng/mL or higher group had an 11.8% higher absolute mortality rate than placebo patients.

The investigators say the association between SDC and mortality persisted after multivariate adjustment.

“Given that no study has demonstrated any substantive clinical benefit for higher SDCs, prudent practice would support an SDC of 0.5 ng/mL to 0.8 ng/mL as a revised therapeutic range,” they state.

JAMA, 2003;289:871-878.