Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial
Abstract
Abstract Background The sodium-glucose cotransporter-2 inhibitor empagliflozin decreases the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid (SUA), but the relevance of this effect in patients with HF is unclear. This study aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA. Methods The association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality was investigated in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was studied in relation to SUA as continuous variable, to clinical hyperuricaemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) and in subgroups of patients of tertiles of SUA. Results Hyperuricaemia was prevalent in 53% of patients with no sex differences. Elevated SUA (highest tertile, mean SUA 9.38 ± 1.49 mg/dL) was associated with advanced severity of HF and with worst outcome [composite outcome, hazard ratio (HR) 1.64 (95% confidence interval, CI 1.28–2.10); cardiovascular mortality, HR 1.98 (95% CI 1.35–2.91); all-cause mortality, HR 1.8 (95% CI 1.29–2.49), all P < 0.001] in multivariate adjusted analyses, as compared with the lowest tertile. SUA was reduced following treatment with empagliflozin at 4 weeks (vs.…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 3,676 participants or records.
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