BACKGROUND Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. OBJECTIVES The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF. METHODS This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF). RESULTS Hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95% CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95% CI: 1.08-1.86]; P = 0.01). SUA was reduced early (after 4 weeks vs placebo -0.99 ± 0.03 mg/dL; P < 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95% CI: 0.51-0.76]; P < 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95% CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07). CONCLUSIONS Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.

中文翻译：

---

Empagliflozin 在射血分数保留的心力衰竭中抑制尿酸和 SGLT2：EMPEROR 保留试验。


背景钠-葡萄糖协同转运蛋白 2 （SGLT2） 抑制剂可改善心力衰竭 （HF） 患者的预后并降低血清尿酸 （SUA）。这种代谢效应对射血分数保留的心力衰竭 （HFpEF） 患者的相关性尚不清楚。目的 作者研究了恩格列净对 HFpEF 患者治疗效果 SUA 水平的影响。方法 EMPEROR-Preserved （EMPagliflozin outcomE tRial 在射血分数保留的 chrOnic heaRt 失败患者中的事后分析;NCT03057951） 试验评估了 SUA 降低与试验结局终点（心血管死亡率或 HF 住院的复合主要结局、其各个组成部分和 HFpEF 患者的全因死亡率）相关的临床效果。结果 高尿酸血症 （女性 SUA >5.7 mg/dL，男性 >7.0 mg/dL） 在 49% 的患者中普遍存在。升高的 SUA（最高三分位数 SUA 8.8 ± 1.4 g/dL）与晚期 HF 严重程度和更高的不良结局风险相关（主要终点 HR：1.23 [95% CI：0.98-1.53];P = 0.07;HF 住院 HR：1.42 [95% CI：1.08-1.86];P = 0.01）。SUA 早期降低 （4 周后与安慰剂相比 -0.99 ± 0.03 mg/dL;P < 0.0001）和整个随访过程中，所有预先指定的亚组均减少。恩格列净将高尿酸血症的临床事件（急性痛风、痛风性关节炎或开始抗痛风治疗）降低了 38% （HR： 0.62 [95% CI： 0.51-0.76];P < 0.0001）.主要终点的治疗获益不受基线 SUA 的影响 （HR： 0.79 [95% CI： 0.69-0.90];P = 0.0004）。SUA 的变化与主要终点的治疗获益呈独立相关性 （P = 0.07）。 结论 高尿酸血症是 HFpEF 的常见并发症，与疾病晚期严重程度和不良结局有关。恩格列净诱导 SUA 水平和与高尿酸血症相关的临床事件的快速和持续降低。