Wolfram Doehner, Stefan D Anker, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Andrew J S Coats, João Pedro Ferreira, Ingrid Henrichmoeller, Martina Brueckmann, Elke Schueler, Stuart J Pocock, James L Januzzi, Milton Packer
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The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear.</p><p><strong>Objectives: </strong>The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. 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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).</p><p><strong>Conclusions: </strong>Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. 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Heart failure","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jchf.2024.08.020","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
背景：钠-葡萄糖共转运体 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）。这种代谢效应与射血分数保留型心力衰竭（HFpEF）患者的相关性尚不清楚：作者研究了 Empagliflozin 对 SUA 水平的影响与 HFpEF 患者疗效的关系：这项对EMPEROR-Preserved（EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951）试验的事后分析评估了降低SUA与试验结果终点（HFpEF患者的心血管死亡率或HF住院治疗的复合主要结果、其单个组成部分以及全因死亡率）的关系的临床效果：49%的患者患有高尿酸血症（女性 SUA >5.7 mg/dL，男性 >7.0 mg/dL）。SUA升高（SUA最高三分位数为8.8 ± 1.4 g/dL）与晚期心房颤动严重程度和不良预后风险较高有关（主要终点HR：1.23 [95% CI：0.98-1.53]；P = 0.07；心房颤动住院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 ± 0.03 mg/dL；P < 0.0001）和整个随访期间均有所降低，所有预设亚组的SUA均有所降低。恩格列净可将高尿酸血症临床事件（急性痛风、痛风性关节炎或开始抗痛风治疗）减少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的变化是主要终点治疗获益的独立相关因素（P = 0.07）：结论：高尿酸血症是高频血友病的常见并发症，与晚期疾病严重程度和不良预后有关。Empagliflozin能快速、持续地降低SUA水平，减少与高尿酸血症相关的临床事件。
Uric Acid and SGLT2 Inhibition With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.
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.
期刊介绍：
JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.
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