BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (P.S.J., K.F.D., M.C.P., J.J.V.M.).
Center for Heart Diseases, University Hospital, Wroclaw Medical University, Poland (P.P.).
Circulation. 2021 May 18;143(20):1962-1972. doi: 10.1161/CIRCULATIONAHA.121.053659. Epub 2021 Apr 9.
Patients with heart failure (HF) and reduced ejection fraction will experience multiple hospitalizations for heart failure during the course of their disease. We assessed the efficacy of dapagliflozin on reducing the rate of total (ie, first and repeat) hospitalizations for heart failure in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure).
The total number of HF hospitalizations and cardiovascular deaths was examined by using the proportional-rates approach of Lei-Wei-Yang-Ying and a joint frailty model for each of recurrent HF hospitalizations and time to cardiovascular death. Variables associated with the risk of recurrent hospitalizations were explored in a multivariable Lei-Wei-Yang-Ying model.
Of 2371 participants randomly assigned to placebo, 318 experienced 469 hospitalizations for HF; of 2373 assigned to dapagliflozin, 230 patients experienced 340 admissions. In a multivariable model, factors associated with a higher risk of recurrent HF hospitalizations included higher heart rate, higher N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. In the Lei-Wei-Yang-Ying model, the rate ratio for the effect of dapagliflozin on recurrent HF hospitalizations or cardiovascular death was 0.75 (95% CI, 0.65-0.88), =0.0002. In the joint frailty model, the rate ratio for total HF hospitalizations was 0.71 (95% CI, 0.61-0.82), <0.0001, whereas, for cardiovascular death, the hazard ratio was 0.81 (95% CI, 0.67-0.98), =0.0282.
Dapagliflozin reduced the risk of total (first and repeat) HF hospitalizations and cardiovascular death. Time-to-first event analysis underestimated the benefit of dapagliflozin in HF and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
射血分数降低的心力衰竭（HF）患者在疾病过程中会经历多次心力衰竭住院治疗。我们评估了达格列净降低 DAPA-HF 试验（达格列净和预防心力衰竭不良结局）中心力衰竭总（即首次和重复）住院率的疗效。
采用 Lei-Wei-Yang-Ying 的比例风险方法和复发心力衰竭和心血管死亡时间的联合脆弱性模型，分别检查心力衰竭总住院次数和心血管死亡。在多变量 Lei-Wei-Yang-Ying 模型中探讨了与复发住院风险相关的变量。
2371 名随机分配至安慰剂的患者中，318 名发生 469 次心力衰竭住院；2373 名随机分配至达格列净的患者中，230 名发生 340 次住院。在多变量模型中，与心力衰竭复发住院风险较高相关的因素包括心率较高、N 末端 pro-B 型利钠肽较高和纽约心脏协会（NYHA）心功能分级较高。在 Lei-Wei-Yang-Ying 模型中，达格列净对心力衰竭复发住院或心血管死亡的效果比为 0.75（95%CI，0.65-0.88），=0.0002。在联合脆弱性模型中，心力衰竭总住院的风险比为 0.71（95%CI，0.61-0.82），<0.0001，而心血管死亡的风险比为 0.81（95%CI，0.67-0.98），=0.0282。
达格列净降低了心力衰竭和射血分数降低患者的总（首次和重复）心力衰竭住院风险和心血管死亡风险。首次事件时间分析低估了达格列净在心力衰竭和射血分数降低患者中的获益。
