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 cotransporter 2 (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 12 weeks 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, 324 patients 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 20.1 m (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, 0.72 kg (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 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

射血分数保留的心力衰竭（HFpEF）患者的症状负担重，功能受限，生活质量差。通过针对心脏代谢异常，钠葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂可以改善这些障碍。在这项对 HFpEF 患者进行的多中心随机试验 (NCT03030235) 中，我们评估了 SGLT2 抑制剂达格列净是否改善了堪萨斯城心肌病问卷临床总结评分 (KCCQ-CS)（衡量心力衰竭相关健康状况的一项指标）的主要终点。治疗开始后 12 周。次要终点包括 6 分钟步行测试 (6MWT)、KCCQ 总体总结评分 (KCCQ-OS)、KCCQ-CS 和 -OS 有临床意义的变化，以及体重、利钠肽、糖化血红蛋白和收缩压的变化。总共 324 名患者被随机分配接受达格列净或安慰剂治疗。达格列净改善了 KCCQ-CS（效果大小，5.8 分（95% 置信区间 (CI) 2.3-9.2， P = 0.001），满足预定义的主要终点，因为 KCCQ 总症状评分 (KCCQ-TS) 均有所改善 (5.8分数（95% CI 2.0-9.6， P = 0.003））和身体限制分数（5.3 分（95% CI 0.7-10.0， P = 0.026））达格列净也改善了 6MWT（平均效应大小为 20.1 m（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 分或以上的参与者比例（优势比 (OR)） = 1.73（95% CI 1.05–2.85， P = 0.03））和体重减轻（平均效应大小，0.72 kg（95% CI 0.01–1.42， P = 0.046））其他次要终点没有显着差异。 达格列净和安慰剂之间的不良事件相似（分别为 44 例（27.2%）和 38 例（23.5%）患者。这些结果表明，12 周的达格列净治疗显着改善了患者报告的症状、身体限制和运动功能，并且在慢性 HFpEF 中具有良好的耐受性。