Digoxin may be linked to increased mortality risk

Digoxin may be associated with increased mortality risk, especially in patients with atrial fibrillation, according to a systematic review and meta-analysis.

Researchers looked at English-language studies published in peer-reviewed journals beginning in 1993. Randomized, controlled trials, case-control studies, and cohort studies were included if they examined the relationship between digoxin and all-cause mortality in patients with atrial fibrillation or congestive heart failure and reported effect sizes as hazard ratios. The study results were published online May 4 by the European Heart Journal.

Nineteen trials were included in the meta-analysis. Of these, 9 involved patients with atrial fibrillation, 7 involved patients with congestive heart failure, and 3 involved patients with both conditions. A total of 326,426 patients were included in the studies, with a follow-up period ranging from 0.83 to 4.7 years. The researchers analyzed adjusted mortality results and found that digoxin use was associated with increased relative risk of all-cause mortality versus no digoxin use (hazard ratio, 1.21; 95% CI, 1.07 to 1.38; P<0.01). In the 235,047 patients who had atrial fibrillation, those who were taking digoxin had a higher mortality risk than those who were not (hazard ratio, 1.29; 95% CI, 1.21 to 1.39; P<0.01). A higher mortality risk associated with digoxin was also seen in the 91,379 patients with heart failure, but to a lesser extent (hazard ratio, 1.14; 95% CI, 1.06 to 1.22; P<0.01).

The authors noted that they did not have access to individual patient data, that residual confounding may have affected their results, and that data on digoxin dose or plasma levels were limited. However, they concluded that based on their findings, digoxin therapy appears to be associated with higher mortality risk in patients with atrial fibrillation and those with congestive heart failure, especially the former group. Randomized, controlled trials of dose-adjusted digoxin therapy are needed, the authors wrote. “Until such proper randomized controlled trials are being completed, digoxin should be used with great caution (including monitoring plasma levels), particularly when administered for rate control in AF,” they concluded.