Methods: Patients were randomized (1:1:1) to EMPA 10 mg, 25 mg or PBO. The composite kidney outcome of incident or worsening nephropathy, defined as progression to macroalbuminuria, doubling of serum creatinine, initiation of renal replacement therapy, or death from renal disease, was analyzed in patients with or without HF at baseline. The incidence of first sustained decline in eGFR from baseline of =40% was also evaluated. Cox proportional hazards models were used to investigate the consistency of treatment effect across subgroups.
Results: Of 7020 treated patients, 706 (10.1%) had HF at baseline. Overall, the incidence of kidney outcome events was numerically higher in patients with HF than without HF. In the HF group, EMPA reduced the risk of incident or worsening nephropathy by 47% (HR 0.53 [95% CI: 0.36–0.77]) (Figure), consistent with the effects in the overall study population (treatment interaction p-value: 0.42). EMPA reduced progression to macroalbuminuria by 50% (HR 0.50 [0.33–0.75]). The composite of hard renal endpoints (doubling of serum creatinine, initiation of renal replacement therapy, or death from renal disease) was reduced in the overall trial population, and the effect was consistent in the HF subgroup (HR 0.78 [0.36–1.67]) (Figure). The time to first sustained eGFR decline from baseline of =40% was reduced overall with consistency of effect seen in the HF population (HR 0.66 [0.33–1.33]). All effects in patients with HF were consistent with those in the overall study population (p-values for interaction >0.05).
Conclusions: In the EMPA-REG OUTCOME trial, patients with T2D and concomitant HF at baseline were at high risk of progressive CKD. In this vulnerable population, EMPA reduced the risk of clinically relevant kidney events. The renoprotective effects were observed on a background of standard of care and were consistent with those reported for the overall study population. The potential of empagliflozin to slow CKD progression in patients with HF (with or without diabetes) is being further investigated in ongoing trials in patients with reduced (EMPEROR-Reduced) or preserved ejection fraction (EMPEROR-Preserved).