MUNICH — Patients with heart failure who are treated with digoxin administered according to the standard nomogram risk getting an overdose that might kill them.
“We recommend treating patients who get digoxin with half the dose from the nomogram,” said Kirkwood F. Adams, Jr., M.D., at the annual congress of the European Society of Cardiology.
Half the standard dosage gives most patients a serum level of 0.5-0.9 ng/mL. A post hoc analysis of data collected in the landmark Digitalis Investigation Group (DIG) trial showed that patients with a serum level in this range had a 15%-20% reduced risk of death during follow-up, compared with patients who did not receive digoxin, reported Dr. Adams, a cardiologist at the University of North Carolina in Chapel Hill.
In contrast, patients who had serum levels of 1.2-1.5 ng/mL had a death rate that was 33% higher than that of matched placebo patients.
This risk is believed to be due to the neurohormonal effects of a relatively high serum level of the drug. At lower serum levels, digoxin probably has a small inotropic effect that is safe and beneficial, Dr. Adams told this newspaper.
In the DIG trial, conducted from 1991 to 1995, the 6,800 patients with stable heart failure were randomized to treatment with digoxin or placebo on top of what was standard heart failure treatment at that time.
The primary finding of the study was that digoxin treatment had no effect on mortality compared with placebo, but it did reduce the hospitalization rate (N. Engl. J. Med. 1997;336:525-33).
The post hoc analysis by Dr. Adams and his associates focused on the 1,843 patients in the digoxin arm of the study who had their serum level of the drug checked after they had been on treatment for 4 weeks, an indicator of their steady-state level of the drug. Of the patients who had this test done and entered into their records, 1,458 had a detectable level of drug.
The relationship between serum levels of digoxin after 4 weeks of treatment and mortality was similar in men and women.
The standard nomogram for calculating a digoxin dosage dates to 1974 and takes into account a patient's body mass index and renal function.
But there can be substantial variability in the actual serum level that individual patients maintain from a particular dosage. With the nomogram, most patients receive a dosage of 0.25 mg/day. A better dosage based on these findings would be 0.125 mg/day, Dr. Adams said.
All patients with heart failure who receive digoxin should have their serum level checked after 4 weeks and then have their dosage modified if the level is outside of the 0.5-0.9 ng/mL range, he added.