British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
JAMA Cardiol. 2023 Jun 1;8(6):554-563. doi: 10.1001/jamacardio.2023.0711.
In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF).
To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population.
DESIGN, SETTING, AND PARTICIPANTS: In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022.
Dapagliflozin, 10 mg, once daily or matching placebo.
The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death.
Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF.
In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF.
ClinicalTrials.gov Identifier: NCT03619213.
在 Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) 试验中，达格列净降低了射血分数轻度降低或保留的心衰（HF）患者心力衰竭（HF）恶化的首次事件或心血管死亡的风险。
评估达格列净对该人群总（即首次和复发性）HF 事件和心血管死亡的影响。
设计、地点和参与者：在 DELIVER 试验的这项预设分析中，采用 Lin、Wei、Yang 和 Ying（LWYY）的比例率方法和联合脆弱性模型来检查达格列净对总 HF 事件和心血管死亡的影响。检查了几个亚组，以测试达格列净的效果是否存在异质性，包括左心室射血分数。参与者于 2018 年 8 月至 2020 年 12 月入组，数据于 2022 年 8 月至 10 月进行分析。
达格列净，10mg，每日一次或匹配安慰剂。
结局为 HF 恶化的总发作次数（HF 住院或需要静脉内 HF 治疗的紧急 HF 就诊）和心血管死亡。
在 6263 名纳入患者中，2747 名（43.9%）为女性，平均（SD）年龄为 71.7（9.6）岁。安慰剂组有 1057 次 HF 事件和心血管死亡，达格列净组有 815 次。HF 事件较多的患者具有更严重 HF 的特征，例如更高的 N 末端 B 型利钠肽前体水平、更差的肾功能、更多的 HF 住院史和更长的 HF 持续时间，尽管射血分数与无 HF 事件的患者相似。在 LWYY 模型中，与安慰剂相比，达格列净治疗总 HF 事件和心血管死亡的风险比为 0.77（95%CI，0.67-0.89；P<0.001），而传统首次事件分析的风险比为 0.82（95%CI，0.73-0.92；P<0.001）。在联合脆弱性模型中，总 HF 事件的风险比为 0.72（95%CI，0.65-0.81；P<0.001），心血管死亡的风险比为 0.87（95%CI，0.72-1.05；P=0.14）。HF 住院（无紧急 HF 就诊）和心血管死亡的结果相似，在所有亚组中，包括射血分数定义的亚组，结果也相似。
在 DELIVER 试验中，达格列净降低了总 HF 事件（首次和随后的 HF 住院和紧急 HF 就诊）和心血管死亡的发生率，无论患者特征如何，包括射血分数。
ClinicalTrials.gov 标识符：NCT03619213。
