Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
JACC Heart Fail. 2020 Oct;8(10):811-818. doi: 10.1016/j.jchf.2020.04.008. Epub 2020 Jul 8.
This study assessed the efficacy and safety of dapagliflozin in patients who were or were not taking sacubitril/valsartan at baseline in the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial.
Both the angiotensin receptor neprilysin-inhibitor sacubitril/valsartan and the sodium glucose co-transporter 2 inhibitor dapagliflozin reduced cardiovascular death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Whether either of these classes of drugs influences the effectiveness or safety of the other remains unknown.
DAPA-HF was a 4,744 patient trial that compared dapagliflozin with placebo in patients with HFrEF. Patients were analyzed according to whether they were taking sacubitril/valsartan at randomization. The efficacy of dapagliflozin on the primary composite outcome (CV death or episode of worsening heart failure), its components, and all-cause death was examined according to sacubitril/valsartan and the interaction tested. Predefined safety outcomes were examined by sacubitril/valsartan group.
A total of 508 patients (10.7%) enrolled in DAPA-HF were treated with sacubitril/valsartan at baseline. Patients prescribed sacubitril/valsartan were more likely to be from North America or Europe, to have lower ejection fractions and systolic and diastolic blood pressures, but were similar with respect to age, New York Heart Association functional class, history of diabetes, and use of other evidence-based HF therapies. The benefit of dapagliflozin compared with placebo was similar in patients taking sacubitril/valsartan (hazard ratio: 0.75; 95% confidence interval 0.50 to 1.13) compared with those not taking sacubitril/valsartan (hazard ratio: 0.74; 95% confidence interval 0.65 to 0.86) for the primary endpoint of cardiovascular death or worsening HF; similar findings were observed for secondary endpoints. All measures of safety, including episodes related to hypovolemia, were similar among patients randomized to dapagliflozin or placebo, whether they received background sacubitril/valsartan.
Dapagliflozin was similarly efficacious and safe in patients who were and who were not taking sacubitril/valsartan in the DAPA-HF trial, which suggested that the use of both agents together could further lower morbidity and mortality in patients with HFrEF. (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure [DAPA-HF]; NCT03036124).
本研究评估了达格列净在基线时服用或未服用沙库巴曲缬沙坦的患者中的疗效和安全性，该研究在 DAPA-HF（评估达格列净对射血分数降低的心力衰竭患者心力衰竭恶化或心血管死亡发生率的影响的研究）试验中进行。
血管紧张素受体脑啡肽酶抑制剂沙库巴曲缬沙坦和钠-葡萄糖共转运蛋白 2 抑制剂达格列净均可降低射血分数降低的心力衰竭（HFrEF）患者的心血管死亡和心力衰竭（HF）住院率。这两类药物中的任何一种是否会影响另一种药物的有效性或安全性尚不清楚。
DAPA-HF 是一项纳入 4744 例患者的试验，比较了达格列净与安慰剂在 HFrEF 患者中的疗效。根据随机分组时是否服用沙库巴曲缬沙坦，对患者进行分析。根据沙库巴曲缬沙坦和交互作用检验，评估达格列净对主要复合终点（心血管死亡或心力衰竭恶化事件）、其组成部分和全因死亡的疗效。根据沙库巴曲缬沙坦组检查预先确定的安全性结局。
共有 508 例（10.7%）患者在 DAPA-HF 中基线时接受沙库巴曲缬沙坦治疗。服用沙库巴曲缬沙坦的患者更可能来自北美或欧洲，射血分数和收缩压及舒张压更低，但在年龄、纽约心脏协会功能分级、糖尿病史和其他基于证据的心力衰竭治疗方面相似。与未服用沙库巴曲缬沙坦的患者相比，服用沙库巴曲缬沙坦的患者接受达格列净治疗与安慰剂相比，其主要终点（心血管死亡或心力衰竭恶化）的获益相似（风险比：0.75；95%置信区间 0.50 至 1.13）；次要终点也观察到相似的结果。接受达格列净或安慰剂治疗的患者中，所有安全性指标（包括与血容量不足相关的事件）均相似，无论患者是否接受沙库巴曲缬沙坦背景治疗。
在 DAPA-HF 试验中，服用和未服用沙库巴曲缬沙坦的患者中，达格列净的疗效和安全性相似，这表明这两种药物联合使用可进一步降低射血分数降低的心力衰竭患者的发病率和死亡率。（达格列净和预防心力衰竭不良结局[DAPA-HF]；NCT03036124）。
