BACKGROUND Goals of management in patients with heart failure and reduced ejection fraction include reducing death and hospitalizations, and improving health status (symptoms, physical function, and quality of life). In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), sodium-glucose cotransporter-2 inhibitor, dapagliflozin, reduced death and hospitalizations, and improved symptoms in patients with heart failure and reduced ejection fraction. In this analysis, we examine the effects of dapagliflozin on a broad range of health status outcomes, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). METHODS KCCQ was evaluated at randomization, 4 and 8 months. Patients were divided by baseline KCCQ total symptom score (TSS); Cox proportional hazards models examined the effects of dapagliflozin on clinical events across these subgroups. We also evaluated the effects of dapagliflozin on KCCQ-TSS, clinical summary score, and overall summary score. Responder analyses were performed to compare proportions of dapagliflozin versus placebo-treated patients with clinically meaningful changes in KCCQ at 8 months. RESULTS A total of 4443 patients had available KCCQ at baseline (median KCCQ-TSS, 77.1 [interquartile range, 58.3-91.7]). The effects of dapagliflozin vs placebo on reducing cardiovascular death or worsening heart failure were consistent across the range of KCCQ-TSS (lowest to highest tertile: hazard ratio, 0.70 [95% CI, 0.57-0.86]; hazard ratio, 0.77 [95% CI, 0.61-0.98]; hazard ratio, 0.62 [95% CI, 0.46-0.83]; P for heterogeneity=0.52). Patients treated with dapagliflozin had greater improvement in mean KCCQ-TSS, clinical summary score, and overall summary score at 8 months (2.8, 2.5 and 2.3 points higher versus placebo; P<0.0001 for all). Fewer patients treated with dapagliflozin had a deterioration in KCCQ-TSS (odds ratio, 0.84 [95% CI, 0.78-0.90]; P<0.0001); and more patients had at least small, moderate, and large improvements (odds ratio, 1.15 [95% CI, 1.08-1.23]; odds ratio, 1.15 [95% CI, 1.08-1.22]; odds ratio, 1.14 [95% CI, 1.07-1.22]; number needed to treat=14, 15, and 18, respectively; P<0.0001 for all; results consistent for KCCQ clinical summary score and overall summary score). CONCLUSIONS Dapagliflozin reduced cardiovascular death and worsening heart failure across the range of baseline KCCQ, and improved symptoms, physical function, and quality of life in patients with heart failure and reduced ejection fraction. Furthermore, dapagliflozin increased the proportion of patients experiencing at least small, moderate, and large improvements in health status; these effects were clinically important. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.

中文翻译：

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Dapagliflozin对心力衰竭和射血分数降低的患者的症状，功能和生活质量的影响：DAPA-HF试验的结果。

背景技术心力衰竭和射血分数降低的患者的治疗目标包括减少死亡和住院，以及改善健康状况（症状，身体功能和生活质量）。在DAPA-HF试验（达格列净和预防心力衰竭的不良结果）中，钠葡萄糖共转运蛋白2抑制剂达格列净减少了死亡和住院，并改善了心力衰竭患者的症状和射血分数。在这项分析中，我们使用堪萨斯城心肌病问卷（KCCQ）检查了dapagliflozin对广泛健康状况结果的影响。方法随机，4个月和8个月评估KCCQ。将患者除以基线KCCQ总症状评分（TSS）；考克斯比例风险模型检查了达格列净对这些亚组临床事件的影响。我们还评估了dapagliflozin对KCCQ-TSS，临床总结分数和总体总结分数的影响。进行了响应者分析，以比较在8个月时KCCQ具有临床意义变化的达格列净与安慰剂治疗患者的比例。结果共有4443名患者在基线时可获得KCCQ（中位KCCQ-TSS，77.1 [四分位间距，58.3-91.7]）。在KCCQ-TSS范围内，达格列净vs安慰剂对减少心血管疾病死亡或加重心力衰竭的作用是一致的（最低至最高三分位数：危险比，0.70 [95％CI，0.57-0.86]；危险比，0.77 [95％] CI：0.61-0.98]；危险比：0.62 [95％CI，0.46-0.83]；异质性P = 0.52）。达格列净治疗的患者在8个月时的平均KCCQ-TSS，临床总结得分和总体总结得分均有较大改善（与安慰剂相比分别提高了2.8、2.5和2.3点；所有指标均P <0.0001）。接受达格列净治疗的患者中KCCQ-TSS恶化的几率降低（比值比为0.84 [95％CI，0.78-0.90]； P <0.0001）；且更多的患者至少有小，中，大的改善（赔率，1.15 [95％CI，1.08-1.23]；优势比，1.15 [95％CI，1.08-1.22]；优势比，1.14 [95％CI，95％CI ，1.07-1.22]；需要治疗的数量分别为14、15和18；所有P <0.0001；结果与KCCQ临床总结分数和总体总结分数一致。结论达格列净在基线KCCQ范围内可减少心血管疾病的死亡和恶化的心力衰竭，并改善症状，身体机能，心力衰竭和射血分数降低的患者的生活质量。此外，达格列净增加了至少部分改善了健康状况的患者的比例；这些作用在临床上很重要。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT03036124。