美国密苏里大学堪萨斯分校Mikhail N. Kosiborod研究小组完成SGLT2抑制剂达格列净治疗射血分数保留型心力衰竭的临床试验。相关论文于2021年10月28日在线发表在《自然—医学》杂志上。

研究人员表示，心力衰竭和射血分数保留（HFpEF）患者的症状和功能限制负担很重，而且生活质量很差。通过针对心脏代谢异常，钠葡萄糖共转运体2（SGLT2）抑制剂可以改善这些障碍。

在一项针对HFpEF患者的多中心随机试验（NCT03030235）中，研究人员评估了SGLT2抑制剂达格列净是否能在治疗开始后的12周内改善堪萨斯城心肌病问卷临床总结评分（KCCQ-CS）这一衡量心衰相关健康状况的主要终点。次要终点包括6分钟步行测试（6MWT）、KCCQ总分（KCCQ-OS）、KCCQ-CS和-OS的临床意义的变化，以及体重、钠尿肽、糖化血红蛋白和收缩压的变化。总共有324名患者被随机分配到达格列净或安慰剂。

达帕格列净改善了KCCQ-CS（效应大小，5.8分（95%置信区间（CI）2.3-9.2，P=0.001），达到了预定的主要终点，这是由于KCCQ总症状评分（KCCQ-TS）（5.8分（95%CI 2.0-9.6，P=0.003））和身体限制评分（5.3分（95%CI 0.7-10.0，P=0.026））的改善。达格列净还改善了6MWT（平均效应大小为20.1米（95% CI 5.6-34.7，P=0.007））、KCCQ-OS（4.5分（95% CI 1.1-7.8，P=0. 009），KCCQ-OS改善5分或更多的参与者比例（几率（OR）=1.73（95% CI 1.05-2.85，P=0.03））和体重减少（平均效应大小，0.72公斤（95% CI 0.01-1.42，P=0.046））。其他次要终点没有明显差异。达格列净和安慰剂之间的不良事件相似（分别为44名（27.2%）与38名（23.5%）患者）。

这些结果表明，12周的达格列净治疗可显著改善患者报告的症状、身体限制和运动功能，并且对慢性HFpEF的耐受性良好。

附：英文原文

Title: The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial

Author: Nassif, Michael E., Windsor, Sheryl L., Borlaug, Barry A., Kitzman, Dalane W., Shah, Sanjiv J., Tang, Fengming, Khariton, Yevgeniy, Malik, Ali O., Khumri, Taiyeb, Umpierrez, Guillermo, Lamba, Sumant, Sharma, Kavita, Khan, Sadiya S., Chandra, Lokesh, Gordon, Robert A., Ryan, John J., Chaudhry, Sunit-Preet, Joseph, Susan M., Chow, Chen H., Kanwar, Manreet K., Pursley, Michael, Siraj, Elias S., Lewis, Gregory D., Clemson, Barry S., Fong, Michael, Kosiborod, Mikhail N.

Issue&Volume: 2021-10-28

Abstract: Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P=0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P=0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P=0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1m (95% CI 5.6–34.7, P=0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P=0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR)=1.73 (95% CI 1.05–2.85, P=0.03)) and reduced weight (mean effect size, 0.72kg (95% CI 0.01–1.42, P=0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

DOI: 10.1038/s41591-021-01536-x

Source: https://www.nature.com/articles/s41591-021-01536-x