Background:Effective therapies for HFrEF usually reduce NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and it is important to establish whether new treatments are effective across the range of NT-proBNP.Methods:We evaluated both these questions in the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. Patients in New York Heart Association functional class II to IV with a left ventricular ejection fraction ≤40% and a NT-proBNP level ≥600 pg/mL (≥600 ng/L; ≥400 pg/mL if hospitalized for HF within the previous 12 months or ≥900 pg/mL if atrial fibrillation/flutter) were eligible. The primary outcome was the composite of an episode of worsening HF or cardiovascular death.Results:Of the 4744 randomized patients, 4742 had an available baseline NT-proBNP measurement (median, 1437 pg/mL [interquartile range, 857–2650 pg/mL]). Compared with placebo, treatment with dapagliflozin significantly reduced NT-proBNP from baseline to 8 months (absolute least-squares mean reduction, −303 pg/mL [95% CI, −457 to −150 pg/mL]; geometric mean ratio, 0.92 [95% CI, 0.88–0.96]). Dapagliflozin reduced the risk of worsening HF or cardiovascular death, irrespective of baseline NT-proBNP quartile; the hazard ratio for dapagliflozin versus placebo, from lowest to highest quartile was 0.43 (95% CI, 0.27–0.67), 0.77 (0.56–1.04), 0.78 (0.60–1.01), and 0.78 (0.64–0.95); P for interaction=0.09. Consistent benefits were observed for all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement (≥5 points) in Kansas City Cardiomyopathy Questionnaire total symptom score (P for interaction=0.99) and decreased the proportion with a deterioration ≥5 points (P for interaction=0.87) across baseline NT-proBNP quartiles.Conclusions:In patients with HFrEF, dapagliflozin reduced NT-proBNP by 300 pg/mL after 8 months of treatment compared with placebo. In addition, dapagliflozin reduced the risk of worsening HF and death, and improved symptoms, across the spectrum of baseline NT-proBNP levels included in DAPA-HF.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

中文翻译：

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根据 N 端 Pro-B 型利钠肽，达格列净在减少射血分数的心力衰竭中的疗效和安全性：来自 DAPA-HF 试验的见解

背景：HFrEF 的有效疗法通常会降低 NT-proBNP（N 末端前 B 型利钠肽）水平，重要的是确定新疗法是否在 NT-proBNP 范围内有效。方法：我们评估了这两种方法DAPA-HF（达格列净和预防心力衰竭不良结果）试验中的问题。左心室射血分数≤40% 和 NT-proBNP 水平≥600 pg/mL（≥600 ng/L；≥400 pg/mL，如果之前因心力衰竭住院，则为纽约心脏协会 II 至 IV 级患者） 12 个月或≥900 pg/mL，如果心房颤动/扑动）符合条件。主要结果是心衰恶化或心血管死亡的复合事件。结果：在 4744 名随机分组的患者中，4742 名有可用的基线 NT-proBNP 测量值（中位数，1437 pg/mL [四分位距，857–2650 皮克/毫升]）。与安慰剂相比，达格列净治疗可显着降低 NT-proBNP 从基线到 8 个月（绝对最小二乘平均降低，-303 pg/mL [95% CI，-457 至 -150 pg/mL]；几何平均比，0.92 [95% CI，0.88–0.96]）。无论基线 NT-proBNP 四分位数如何，达格列净均降低了心衰恶化或心血管死亡的风险；dapagliflozin 与安慰剂的风险比从最低到最高四分位数分别为 0.43（95% CI，0.27-0.67）、0.77（0.56-1.04）、0.78（0.60-1.01）和 0.78（0.64-0.95）；无论基线 NT-proBNP 四分位数如何，达格列净均降低了心衰恶化或心血管死亡的风险；dapagliflozin 与安慰剂的风险比从最低到最高四分位数分别为 0.43（95% CI，0.27-0.67）、0.77（0.56-1.04）、0.78（0.60-1.01）和 0.78（0.64-0.95）；无论基线 NT-proBNP 四分位数如何，达格列净均降低了心衰恶化或心血管死亡的风险；dapagliflozin 与安慰剂的风险比从最低到最高四分位数分别为 0.43（95% CI，0.27-0.67）、0.77（0.56-1.04）、0.78（0.60-1.01）和 0.78（0.64-0.95）；交互作用的P = 0.09。在全因死亡率方面观察到一致的益处。与安慰剂相比，达格列净增加了堪萨斯城心肌病问卷总症状评分（P =0.99）有显着改善（≥5分）的患者比例，降低了≥5分恶化的患者比例（P交互作用=0.87) 基线 NT-proBNP 四分位数。结论：在 HFrEF 患者中，与安慰剂相比，达格列净治疗 8 个月后 NT-proBNP 降低 300 pg/mL。此外，dapagliflozin 降低了 HF 恶化和死亡的风险，并改善了症状，在 DAPA-HF 中包含的基线 NT-proBNP 水平范围内。注册：URL：https://www.clinicaltrials.gov；唯一标识符：NCT03036124。