BACKGROUND The DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) showed that dapagliflozin added to other guideline-recommended therapies reduced the risk of mortality and heart failure hospitalization and improved symptoms in patients with heart failure and reduced ejection fraction. We examined the effects of dapagliflozin according to age, given potential concerns about the efficacy and safety of therapies in the elderly. METHODS Patients in New York Heart Association functional class II or greater with a left ventricular ejection fraction ≤40% and a modest elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide) were eligible. Key exclusion criteria included systolic blood pressure <95 mm Hg and estimated glomerular filtration rate <30 mL·min-1·1.73 m-2. The primary outcome was the composite of an episode of worsening heart failure (heart failure hospitalization or urgent heart failure visit) or cardiovascular death, whichever occurred first. RESULTS A total of 4744 patients 22 to 94 years of age (mean age, 66.3 [SD 10.9] years) were randomized: 636 patients (13.4%) were <55 years of age, 1242 (26.2%) were 55 to 64 years of age, 1717 (36.2%) were 65 to 74 years of age, and 1149 (24.2%) were ≥75 years of age. The rate of the primary outcome (per 100 person-years, placebo arm) in each age group was 13.6 (95% CI, 10.4-17.9), 15.7 (95% CI, 13.2-18.7), 15.1 (95% CI, 13.1-17.5), and 18.0 (95% CI, 15.2-21.4) with corresponding dapagliflozin/placebo hazard ratios of 0.87 (95% CI, 0.60-1.28), 0.71 (95% CI, 0.55-0.93), 0.76 (95% CI, 0.61-0.95), and 0.68 (95% CI, 0.53-0.88; P for interaction=0.76). Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and symptoms. Although adverse events and study drug discontinuation increased with age, neither was significantly more common with dapagliflozin in any age group. CONCLUSIONS Dapagliflozin reduced the risk of death and worsening heart failure and improved symptoms across the broad spectrum of age studied in DAPA-HF. There was no significant imbalance in tolerability or safety events between dapagliflozin and placebo, even in elderly individuals. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT03036124.

中文翻译：

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Dapagliflozin在根据年龄减少射血分数的心力衰竭中的疗效和安全性：DAPA-HF的见解。

背景技术DAPA-HF试验（达格列净和预防心力衰竭的不良结果）表明，达格列净与其他指南推荐的治疗方法相结合，可降低死亡率和心力衰竭住院的风险，并改善心力衰竭患者的症状并减少射血分数。考虑到对老年人的疗效和安全性的潜在担忧，我们根据年龄检查了达格列净的作用。方法符合纽约心脏协会功能性II级或更高水平，左心室射血分数≤40％且NT-proBNP（N端pro-B型利尿钠肽）适度升高的患者是合格的。关键排除标准包括收缩压<95 mm Hg和估计的肾小球滤过率<30 mL·min-1·1.73 m-2。主要结局是心力衰竭加重（心力衰竭住院或紧急心力衰竭就诊）或心血管死亡发作的综合结果，以较先发生者为准。结果共有4744名22至94岁的患者（平均年龄为66.3 [SD 10.9]岁）被随机分组​​：636名患者（13.4％）为<55岁，1242（26.2％）为55至64岁。年龄为65至74岁的年龄为1717岁（36.2％），≥75岁的年龄为1149（24.2％）。每个年龄段的主要结局发生率（每100人年，安慰剂组）为13.6（95％CI，10.4-17.9），15.7（95％CI，13.2-18.7），15.1（95％CI，13.1） -17.5）和18.0（95％CI，15.2-21.4），达格列净/安慰剂的危险比分别为0.87（95％CI，0.60-1.28），0.71（95％CI，0.55-0.93），0.76（95％CI） ，0.61-0.95）和0.68（95％CI，0.53-0.88；交互作用的P = 0.76）。观察到主要结局，全因死亡率和症状的组成部分具有一致的益处。尽管不良反应和研究药物的停用随着年龄的增长而增加，但在任何年龄组中，达格列净都不明显更常见。结论在DAPA-HF研究中，达格列净降低了广泛年龄段的死亡风险和心力衰竭，并改善了症状。达格列净与安慰剂之间的耐受性或安全性事件之间均无显着失衡，即使在老年人中也是如此。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT03036124。达格列净在任何年龄组中都没有明显更常见。结论在DAPA-HF研究中，达格列净降低了广泛年龄段的死亡风险和心力衰竭，并改善了症状。达格列净与安慰剂之间在耐受性或安全性事件上没有显着的失衡，即使在老年患者中也是如此。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT03036124。达格列净在任何年龄组中都没有明显更常见。结论在DAPA-HF研究中，达格列净降低了广泛年龄段的死亡风险和心力衰竭，并改善了症状。达格列净与安慰剂之间的耐受性或安全性事件之间均无显着失衡，即使在老年人中也是如此。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：NCT03036124。