Effects of empagliflozin on hyperuricaemia and heart failure

Empagliflozin, a sodium-glucose cotransporter-2 inhibitor, induces a rapid and sustained reduction in serum uric acid levels and decreases the risk of cardiovascular death or hospitalization for heart failure. These findings of a secondary analysis of data from the EMPEROR-Reduced study were published in the European Heart Journal. The post hoc analysis1 evaluates the relationship between serum uric acid (SUA) levels and the dynamics of BSU with the effects of empagliflozin treatment on hospitalization, mortality and renal function in patients with heart failure (HF) with reduced ejection fraction (ICFEr). Read: DOAC dosing in older patients with nonvalvular atrial fibrillation Elements of methodology The EMPEROR-Reduced2 study is a randomized, double-blind, parallel-group, placebo-controlled trial that evaluated the effects of empagliflozin on the morbidity and mortality of patients with rICFE (EF ≤ 40%) and that were receiving all appropriate treatments for HF. Patients were randomly assigned in a 1:1 ratio to receive empagliflozin 10 mg once daily or a placebo, in addition to their usual treatments. BUA was measured (in mg/dL) at four and 12 weeks, then every six months for the duration of treatment (median follow-up approximately 20 months). Hyperuricaemia was defined as BUN > 7.0 mg/dL for males and > 5.7 mg/dL for females. The primary endpoint was a composite of cardiovascular death or HF hospitalization. The first secondary endpoint was the occurrence of all hospitalizations for HF (first event and recurrent events). Read: Will angiotensin receptor II blockers play a role in epilepsy prevention? Principle results Of the 3,730 patients in the trial, 3676 (98.6%) with an initial assessment of BUA were included in the analysis. The mean AUS was 7.29 ± 2.06 mg/dL in males and 6.54 ± 2.03 mg/dL in females. Hyperuricemia was prevalent in 53% of patients, with no gender difference. A high mean BUA level (9.38 ± 1.49 mg/dL) was associated with HF severity and worse outcomes in terms of composite measures, cardiovascular mortality, or all-cause mortality, compared with a low BUA rate (4.99 ± 0.84; p < 0.001 for all comparisons). In the placebo group, the risk of clinical outcomes increased along with BUA rates for the primary endpoint, first or recurrent hospitalization, cardiovascular mortality, and all-cause mortality (p < 0.001 for all tendencies). Empaglifozin caused a significant reduction in uric acid levels within four weeks of starting treatment (empagliflozin vs placebo: mean change -1.11 ± 0.03 mg/dL, p < 0.01) and the magnitude of the effect remained stable throughout the treatment period. Empagliflozin reduced clinically relevant hyperuricemia events by 32% (HR: 0.68; 95% CI: 0.52 – 0.89; p=0.004). In conclusion, hyperuricemia has already been identified as a pathophysiological characteristic of HF and as a marker of increased oxidative stress.3-5 Like previous studies, this one shows that high levels of BUA are associated with reduced functional capacity, disease severity and advanced mortality in HF. In addition, treatment with empagliflozin induced a rapid and sustained response of BSU and decreased the risk of hyperuricaemic events. References 1. Doehner, W. et al. (2022). Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial. European Heart Journal 43, 3435–3446. 2. Packer M et al. (2019). Evaluation of the effect of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality of patients with chronic heart failure and a reduced ejection fraction: rationale for and design of the EMPEROR-reduced trial. Eur J Heart Fail 21, 1270–1278. 3. Leyva F et al. (1998). Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 19, 1814–1822. 4. Leyva F et al. (1997). Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 18, 858–865. 5. Mantovani A. et al. (2018). Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: a post-hoc analysis of the GISSI-HF (gruppo italiano per lo studio della sopravvivenza nella insufficienza Cardiaca-heart failure) trial. Metabolism 83, 205–215. This article has been translated from its original French and originally appeared on our sister site Profession Santé. Read: One-stop shop: New Canadian cardiovascular disease guideline pulls together dozens of recommendations

Effects of empagliflozin on hyperuricaemia and heart failure

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