Saint Luke's Mid America Heart Institute, Kansas City, MO (M.N.K., M.E.N.).
School of Medicine, University of Missouri-Kansas City (M.N.K., M.E.N.).
Circulation. 2022 Jul 26;146(4):279-288. doi: 10.1161/CIRCULATIONAHA.122.059725. Epub 2022 Apr 4.
Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized).
Patients hospitalized for acute heart failure were randomized to empagliflozin 10 mg daily or placebo for 90 days. The KCCQ was assessed at randomization and 15, 30, and 90 days. The effects of empagliflozin on the primary end point of clinical benefit (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in KCCQ Total Symptom Score [TSS] change from baseline to 90 days) were examined post hoc across the tertiles of baseline KCCQ-TSS. In prespecified analyses, changes (randomization to day 90) in KCCQ domains, including TSS, physical limitations, quality of life, clinical summary, and overall summary scores were evaluated using a repeated measures model.
In total, 530 patients were randomized (265 each arm). Baseline KCCQ-TSS was low overall (mean [SD], 40.8 [24.0] points). Empagliflozin-treated patients experienced greater clinical benefit across the range of KCCQ-TSS, with no treatment effect heterogeneity (win ratio [95% CIs] from lowest to highest tertile: 1.49 [1.01-2.20], 1.37 [0.94-1.99], and 1.48 [1.00-2.20], respectively; for interaction=0.94). Beneficial effects of empagliflozin on health status were observed as early as 15 days and persisted through 90 days, at which point empagliflozin-treated patients experienced a greater improvement in KCCQ TSS, physical limitations, quality of life, clinical summary, and overall summary (placebo-adjusted mean differences [95% CI]: 4.45 [95% CI, 0.32-8.59], =0.03; 4.80 [95% CI, 0.00-9.61], =0.05; 4.66 [95% CI, 0.32-9.01], =0.04; 4.85 [95% CI, 0.77-8.92], =0.02; and 4.40 points [95% CI, 0.33-8.48], =0.03, respectively).
Initiation of empagliflozin in patients hospitalized for acute heart failure produced clinical benefit regardless of the degree of symptomatic impairment at baseline, and improved symptoms, physical limitations, and quality of life, with benefits seen as early as 15 days and maintained through 90 days.
URL: https://www.
gov; Unique identifier: NCT0415775.
因急性心力衰竭住院的患者健康状况较差，包括症状负担高、身体受限以及生活质量较差。SGLT2（钠-葡萄糖共转运蛋白 2）抑制剂可改善慢性心力衰竭患者的健康状况，但它们对急性心力衰竭患者的这些结局的影响尚未得到充分描述。我们通过堪萨斯城心肌病问卷（KCCQ），在 EMPULSE 试验（接受急性心力衰竭稳定治疗的患者中使用恩格列净）中研究了 SGLT2 抑制剂恩格列净对症状、身体受限和生活质量的影响。
因急性心力衰竭住院的患者被随机分配至恩格列净 10mg 每日一次或安慰剂治疗 90 天。在随机分组时以及第 15、30 和 90 天评估 KCCQ。使用事后分析，根据基线 KCCQ-TSS 的三分位数，检查恩格列净对主要终点临床获益（全因死亡、心力衰竭事件以及与基线相比 KCCQ 总症状评分[TSS]变化 5 分或更多的复合终点）的影响。在预先指定的分析中，使用重复测量模型评估 KCCQ 各域（包括 TSS、身体受限、生活质量、临床总结和总体总结评分）的变化（从随机分组到第 90 天）。
共有 530 例患者被随机分组（每组 265 例）。总体而言，基线 KCCQ-TSS 较低（平均[标准差]，40.8[24.0]分）。恩格列净治疗的患者在整个 KCCQ-TSS 范围内经历了更大的临床获益，且治疗效果无异质性（最低到最高三分位数的赢比值[95%CI]：1.49[1.01-2.20]、1.37[0.94-1.99]和 1.48[1.00-2.20]；=0.94）。恩格列净在 15 天内即可观察到对健康状况的有益影响，并持续至 90 天，此时恩格列净治疗的患者 KCCQ TSS、身体受限、生活质量、临床总结和总体总结均有更大改善（安慰剂调整后的平均差异[95%CI]：4.45[95%CI，0.32-8.59]，=0.03；4.80[95%CI，0.00-9.61]，=0.05；4.66[95%CI，0.32-9.01]，=0.04；4.85[95%CI，0.77-8.92]，=0.02；和 4.40 分[95%CI，0.33-8.48]，=0.03）。
急性心力衰竭住院患者起始使用恩格列净可带来临床获益，无论基线时症状严重程度如何，且可改善症状、身体受限和生活质量，益处可在 15 天内出现，并持续至 90 天。
美国国立卫生研究院临床试验注册数据库；独特标识符：NCT0415775。
