BHF Cardiovascular Research Centre, University of Glasgow, UK (A.M.J., P.D., K.F.D., P.S.J., J.J.V.M.).
Department of Cardiology, University of Minnesota, Minneapolis (I.S.A.).
Circulation. 2020 Sep 15;142(11):1040-1054. doi: 10.1161/CIRCULATIONAHA.120.047077. Epub 2020 Jul 16.
In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo.
We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms.
Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on <40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking >40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively ( for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow-up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization.
The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
在 DAPA-HF 试验（达格列净与心力衰竭不良结局预防）中，钠-葡萄糖协同转运蛋白 2 抑制剂达格列净降低了射血分数降低的心力衰竭患者心力衰竭恶化和死亡的风险。我们研究了达格列净与安慰剂相比，与背景利尿剂治疗和随机分配至达格列净或安慰剂后利尿剂治疗的变化相关的疗效和耐受性。
我们研究了以下亚组的研究治疗效果：无利尿剂和利尿剂剂量等效于呋塞米<40、40 和>40mg 每日基线。我们研究了主要复合终点心血管死亡或心力衰竭恶化事件及其组成部分、全因死亡和症状。
在 4616 名可分析患者中，736 名（15.9%）无利尿剂，1311 名（28.4%）<40mg，1365 名（29.6%）40mg，1204 名（26.1%）>40mg。与安慰剂相比，达格列净降低了每个亚组的主要终点风险：风险比分别为 0.57（95%CI，0.36-0.92）、0.83（95%CI，0.63-1.10）、0.77（95%CI，0.60-0.99）和 0.78（95%CI，0.63-0.97）（交互检验=0.61）。服用任何利尿剂的患者的风险比为 0.78（95%CI，0.68-0.90）。症状改善和治疗耐受性在利尿剂亚组中一致。在随访期间，大多数患者的利尿剂剂量没有变化，随机分配后达格列净组和安慰剂组的平均利尿剂剂量没有差异。
在 DAPA-HF 研究中检查的利尿剂亚组中，达格列净的疗效和安全性一致。登记：网址：https://www.clinicaltrials.gov；独特标识符：NCT03036124。
