New Monitoring Recommendations for Digoxin During the Last Decade Are Associated With Decreased Serum Digoxin Concentrations in Patient Samples

Digoxin has long been used to manage atrial fibrillation and heart failure. While therapeutic drug monitoring (TDM) became available in the late 1960s, recent studies suggest increased mortality at serum levels > 1.0 ng/mL, prompting reassessment of the traditionally accepted range (0.8-2.0 ng/mL). This study evaluated trends in digoxin concentrations from 2004 to 2024 to assess alignment with updated recommendations. We retrospectively analysed 37 489 routine digoxin measurements from Uppsala University Hospital (2004-2024), including patient age, sex, sampling date and digoxin levels. Analytical platforms changed from Abbott's Architect to Roche's Cobas Pro during the study period. Trends over time and sex differences were evaluated. Of the samples, 17 771 were from males (median age 77) and 19 718 from females (median age 83). Median digoxin concentrations were 0.9 nmol/L for males and 1.0 nmol/L for females. About 30% of samples exceeded 1.2 nmol/L. Digoxin concentrations decreased over time (Spearman R = -0.191, p < 0.000001), particularly in higher values. Associations with age were modest. Serum digoxin levels have declined over the past two decades, reflecting evolving guidelines, though elevated levels remain common, highlighting the need for ongoing clinical-laboratory alignment.