Doehner Wolfram, Anker Stefan D, Butler Javed, Zannad Faiez, Filippatos Gerasimos, Coats Andrew J S, Ferreira João Pedro, Henrichmoeller Ingrid, Brueckmann Martina, Schueler Elke, Pocock Stuart J, Januzzi James L, Packer Milton
Berlin Institute of Health - Center for Regenerative Therapies, and Department of Cardiology (CVK), Deutsches Herzzentrum der Charité and German Centre for Cardiovascular Research Partner Site Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Berlin Institute of Health - Center for Regenerative Therapies, and Department of Cardiology (CVK), Deutsches Herzzentrum der Charité and German Centre for Cardiovascular Research Partner Site Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany.
JACC Heart Fail. 2024 Dec;12(12):2057-2070. doi: 10.1016/j.jchf.2024.08.020. Epub 2024 Oct 23.
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.
The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF.
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).
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).
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.
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）水平。这种代谢效应在射血分数保留的心力衰竭（HFpEF）患者中的相关性尚不清楚。
作者研究了恩格列净对HFpEF患者SUA水平的影响及其治疗效果。
这项对EMPEROR-Preserved（恩格列净治疗射血分数保留的慢性心力衰竭患者试验；NCT03057951）试验的事后分析评估了SUA降低与试验结局终点（心血管死亡或HF住院的复合主要终点、其各个组成部分以及HFpEF患者的全因死亡率）之间的临床关系。
49%的患者存在高尿酸血症（女性SUA>5.7mg/dL，男性>7.0mg/dL）。SUA升高（最高三分位数SUA为8.8±1.4g/dL）与HF严重程度加重及不良结局风险较高相关（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在早期（4周后与安慰剂相比-0.99±0.03mg/dL；P<0.0001）及整个随访期间均降低，所有预先指定的亚组均有降低。恩格列净使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）减少了38%（HR：0.62[95%CI：0.51-0.76]；P<0.0001）。对主要终点的治疗益处不受基线SUA的影响（HR：0.79[95%CI：0.69-0.90]；P=0.0004）。SUA的变化是对主要终点治疗益处的独立相关因素（P=0.07）。
高尿酸血症是HFpEF的常见并发症，与疾病严重程度加重和不良结局相关。恩格列净可使SUA水平及与高尿酸血症相关的临床事件迅速且持续降低。
