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 ¡Ý20 % increase in estimated glomerular filtration rate (eGFR). IRF occurred in 15.5 % of the population (mean improvement in eGFR 34.5 ¡À 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).
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.