Empagliflozin may reduce serum uric acid in HF patients, lower mortality risk: EMPEROR-reduced trial
Germany: In patients with heart failure, hyperuricemia is a common comorbidity and is an independent predictor of advanced disease severity and increased mortality, the researchers' state in a study published in European Heart Journal.
Findings from the EMPEROR-reduced trial showed that treatment with empagliflozin rapidly reduced the levels of serum uric acid (SUA) and of clinical events due to hyperuricemia. Empagliflozin's benefit on the primary outcome was seen independently of SUA.
Previous studies have shown that the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin lowers the risk of cardiovascular death or hospitalization for heart failure (HF) in patients with HF with reduced ejection fraction. Empagliflozin reduces serum uric acid but there is no clarity on the relevance of this effect in HF patients.
Against the above background, Wolfram Doehner, Berlin Institute of Health Center for Regenerative Therapies, Charité Universitätsmedizin Berlin, Augustenburger Platz, Berlin, Germany, and colleagues aimed to investigate the effect of empagliflozin on SUA levels and the therapeutic efficacy of empagliflozin in relation to SUA.
For this purpose, the researchers investigated the association between SUA and the composite primary outcome of cardiovascular death or hospitalization for worsening HF, its components, and all-cause mortality in 3676 patients of the EMPEROR-Reduced trial (98.6% of the study cohort). The treatment effect of empagliflozin was examined in association with SUA as a continuous variable, in clinical hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) and in subgroups of patients with tertiles of SUA.
Key findings of the study include:
- 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 the worst outcome [composite outcome, hazard ratio (HR) 1.64; cardiovascular mortality, HR 1.98; all-cause mortality, HR 1.8] in multivariate-adjusted analyses, as compared with the lowest tertile. SUA was reduced following treatment with empagliflozin at 4 weeks (vs. placebo: −1.12 ± 0.04 mg/dL) and remained lower throughout follow-up, with a similar reduction in all prespecified subgroups.
- Empagliflozin reduced events of clinically relevant hyperuricemia (acute gout, gouty arthritis, or initiation of anti-gout therapy) by 32% [HR 0.68].
- The beneficial effect of empagliflozin on the primary endpoint was independent of baseline SUA [HR 0.76) and of the change in SUA at 4 weeks [HR 0.81].
- As a hypothesis-generating finding, an interaction between SUA and treatment effect suggested a benefit of empagliflozin on mortality (cardiovascular and all-cause mortality) in patients with elevated SUA.
To conclude, empagliflozin induced a fast and sustained lowering of SUA levels and decreased events of clinically relevant hyperuricemia by 32%.
Reference:
Wolfram Doehner, Stefan D Anker, Javed Butler, Faiez Zannad, Gerasimos Filippatos, João Pedro Ferreira, Afshin Salsali, Carolyn Kaempfer, Martina Brueckmann, Stuart J Pocock, James L Januzzi, Milton Packer, Uric acid and sodium-glucose cotransporter-2 inhibition with empagliflozin in heart failure with reduced ejection fraction: the EMPEROR-reduced trial, European Heart Journal, 2022;, ehac320, https://doi.org/10.1093/eurheartj/ehac320
