Influence of endpoint definitions on the effect of empagliflozin on major renal outcomes in the EMPEROR‐Preserved trial
Abstract
Large-scale trials have evaluated the effects of treatments on major renal outcomes, but the definition of a renal event has varied from trial to trial. In defining a renal event, trialists included patients who needed renal replacement therapy or whose estimated glomerular filtration rate (eGFR) declined to 40% were randomly assigned to placebo or empagliflozin for a median of 26 months. Empagliflozin reduced the primary endpoint of cardiovascular death or heart failure hospitalization by 21% [hazard ratio 0.79 (95% CI 0.69–0.90)] and decreased total (first and recurrent) hospitalizations for heart failure by 27% [hazard ratio 0.73 (95% CI 0.61–0.88)].3 When the influence of baseline ejection fraction on these results was evaluated according to prespecified subgroups of 41–49%, 50–59% and ≥60%, baseline ejection fraction did not influence the effect of empagliflozin on the primary endpoint. However, ejection fraction did influence the effect of empagliflozin on total hospitalizations for heart failure (Ptrend = 0.008), with an attenuated effect in patients with an ejection fraction ≥60%.4 In contrast to these favourable effects of empagliflozin on heart failure outcomes in EMPEROR-Preserved, empagliflozin did not exert a favourable effect on major renal outcomes using the EMPEROR definition,5 which relied on a threshold of a sustained ≥40% decrease in eGFR and did not include the occurrence of renal death. The hazard ratio for the effect of empagliflozin on major renal…
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