Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction
Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction
复制标题
达格列净对射血分数降低的心力衰竭患者的症状、功能和生活质量的影响
作者：
M. Kosiborod;P. Jhund;K. Docherty;M. Diez;M. Petrie;S. Verma;J. Nicolau;B. Merkely;M. Kitakaze;D. DeMets;S. Inzucchi;L. Køber;F. Martinez;P. Ponikowski;M. Sabatine;S. Solomon;O. Bengtsson;D. Lindholm;A. Niklasson;M. Sjöstrand;A. Langkilde;J. McMurray
文本中提供了补充数字内容。背景资料：心力衰竭和射血分数降低患者的管理目标包括减少死亡和住院，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不良结局）中，钠-葡萄糖协同转运蛋白-2抑制剂达格列净减少了心力衰竭和射血分数降低患者的死亡和住院率，并改善了症状。在这项分析中，我们使用堪萨斯城心肌病问卷（KCCQ）检查了达格列净对广泛健康状况结局的影响。方法：在随机化、4个月和8个月时评估KCCQ。患者按基线KCCQ总症状评分（TSS）分组;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。我们还评估了达格列净对KCCQ-TSS、临床综合评分和总体综合评分的影响。进行应答者分析，以比较达格列净与安慰剂治疗患者在8个月时KCCQ发生具有临床意义变化的比例。结果：共有4443例患者在基线时有可用的KCCQ（中位KCCQ-TSS，77.1 [四分位距，58.3-91.7]）。在KCCQ-TSS范围内，达格列净与安慰剂相比在降低心血管死亡或心力衰竭恶化方面的作用一致（最低至最高三分位数：风险比，0.70 [95% CI，0.57-0.86];风险比，0.77 [95% CI，0.61-0.98];风险比，0.62 [95% CI，0.46-0.83];异质性P =0.52）。接受达格列净治疗的患者在8个月时平均KCCQ-TSS、临床总结评分和总体总结评分的改善更大（与安慰剂相比高2.8、2.5和2.3分; P均<0.0001）。接受达格列净治疗的患者中KCCQ-TSS恶化的患者较少（比值比，0.84 [95%CI，0.78-0.90]; P<0.0001）;更多的患者至少有小、中、大的改善（比值比，1.15 [95% CI，1.08-1.23];比值比，1.15 [95% CI，1.08-1.22];比值比，1.14 [95% CI，1.07-1.22];需要治疗的人数分别为14、15和18;所有患者P<0.0001;结果与KCCQ临床总结评分和总体总结评分一致）。结论：在基线KCCQ范围内，达格列净降低了心血管死亡和心力衰竭恶化，并改善了心力衰竭和射血分数降低患者的症状、身体功能和生活质量。此外，达格列净增加了健康状况至少有小、中、大改善的患者比例;这些效应具有临床重要性。临床试验注册：URL：https://www.clinicaltrials.gov。唯一标识符：NCT 03036124。
Supplemental Digital Content is available in the text. 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.
影响因子：
120.7
作者：
Flynn, Kathryn E.;Pina, Ileana L.;Whellan, David J.;Lin, Li;Blumenthal, James A.;Ellis, Stephen J.;Fine, Lawrence J.;Howlett, Jonathan G.;Keteyian, Steven J.;Kitzman, Dalane W.;Kraus, William E.;Miller, Nancy Houston;Schulman, Kevin A.;Spertus, John A.;O'Connor, Christopher M.;Weinfurt, Kevin P.
通讯作者：
Weinfurt, Kevin P.
影响因子：
37.8
作者：
Nassif, Michael E.;Windsor, Sheryl L.;Cox, John M.
通讯作者：
Cox, John M.