The impact of serum concentration‐guided digoxin therapy on mortality of heart failure patients: A long‐term follow‐up, propensity‐matched cohort study

BACKGROUND: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC‐guided. AIM: To assess the impact of SDC‐guided digoxin therapy on mortality in HFrEF patients. METHODS: Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC‐guided (target SDC: 0.5‐0.9 ng/mL). All‐cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM). RESULTS: After 7.1 ± 4.7 years follow‐up period (FUP) all‐cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity‐adjusted HR = 1.430; 95% CI = 1.134‐1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all‐cause mortality (HR = 1.750; 95% CI = 1.257‐2.436, P = .001 and HR = 1.687; 95% CI = 1.153‐2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827‐1.570, P = .426), compared to digoxin nonusers. CONCLUSIONS: According to our propensity‐matched analysis, SDC‐guided digoxin therapy was associated with increased all‐cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.