Potential Effects of Digoxin on Long-Term Renal and Clinical Outcomes in Chronic Heart Failure

Abstract Background Digitalis glycosides are known to improve the hemodynamic and neurohormonal perturbations that contribute to heart failure (HF)–induced renal dysfunction (RD). The objective of this study was to determine if randomization to digoxin is associated with improvement in renal function (IRF) and to evaluate if patients with digoxin-induced IRF have improved clinical outcomes. Methods and Results Patients in the Digitalis Investigation Group (DIG) dataset with protocol-driven 1-year serum creatinine levels (performed in a central laboratory; n = 980) were studied. IRF was defined as a postrandomization ≥20% increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5% of the population (mean improvement in eGFR 34.5 ± 15.4%) and was more common in patients randomized to digoxin (adjusted odds ratio 1.6; P = .02). In patients without IRF, digoxin was not associated with reduced death or hospitalization (adjusted hazard ratio [HR] 0.96, 95% CI 0.8–1.2; P = .67). However, in the group with IRF, digoxin was associated with substantially improved hospitalization-free survival (adjusted HR 0.49, 95% CI 0.3–0.8; P = .006; P interaction = .026). Conclusions In this subset of the DIG trial, digoxin was associated with long-term improvement in kidney function and, in patients demonstrating this favorable renal response, reduction in death or hospitalization. Additional research is necessary to confirm these hypothesis-generating findings.