Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
JAMA Cardiol. 2022 Dec 1;7(12):1227-1234. doi: 10.1001/jamacardio.2022.3736.
In 2 trials enrolling patients with heart failure (HF) across the spectrum of ejection fraction (EF), dapagliflozin has been shown to reduce the rate of the composite of worsening HF events or death from cardiovascular (CV) causes.
To examine the effects of dapagliflozin on cause-specific CV and non-CV mortality across the spectrum of EF.
DESIGN, SETTING, AND PARTICIPANTS: This was a participant-level, pooled, prespecified secondary analysis of data from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, or DAPA-HF trial (participant left ventricular EF [LVEF] ≤40%), and Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure, or DELIVER trial (participant LVEF >40%), to assess the effects of randomized treatment on cause-specific mortality. The trials assigned adjacent populations of patients with chronic HF, New York Heart Association class II-IV symptoms, and elevated natriuretic peptides to treatment with dapagliflozin (10 mg, once daily) or placebo. The primary outcome for each study was a composite of worsening HF events (hospitalization or urgent heart failure visits) or CV death. Clinical outcomes, including all deaths, were adjudicated as to cause by clinical end points committees blinded to treatment assignment.
Dapagliflozin vs placebo.
The mode of death in relation to baseline EF was examined, as well as the effect of randomized treatment on cause-specific death in Cox regression models. Relationships with continuous EF were modeled using Poisson regression.
Of 11 007 patients in the pooled data set, there were 1628 deaths during follow-up (mean [SD] age, 71.7 [10.3] years; 1139 male [70.0%]). Of those who died, 872 (53.5%) were ascribed to CV deaths, 487 (29.9%) to non-CV deaths, and 269 (16.5%) to undetermined causes. Of CV deaths, 289 (33.1%; this represented 17.8% of total deaths) were due to HF, 441 (50.6%; 27.1% of total deaths) were sudden, 69 (7.9%; 4.2% of total deaths) were due to stroke, 47 (5.4%; 2.9% of total deaths) to myocardial infarction, and 26 (3.0%; 1.6% of total deaths) were due to other CV causes. The proportion of non-CV deaths was higher in those with higher EF. In the pooled population, across the spectrum of EF, treatment with dapagliflozin was associated with lower rates of CV death (hazard ratio [HR], 0.86; 95% CI, 0.75-0.98; P = .02), principally due to lower rates of sudden death (HR, 0.84; 95% CI, 0.70-1.01; P = .07) and HF death (HR, 0.88; 95% CI, 0.70-1.11; P = .30), with little difference in rates of death from stroke or MI.
In a pooled analysis of patients with HF in the DAPA-HF and DELIVER randomized clinical trials, across the full spectrum of LVEF, dapagliflozin significantly reduced risks of CV death with contributions from lower rates of sudden death and death from progressive HF.
ClinicalTrials.gov Identifier: NCT03036124, NCT03619213.
在两项针对射血分数（EF）不同范围的心衰患者的临床试验中，达格列净已被证明可降低因心血管（CV）原因导致的 HF 恶化事件或死亡的复合发生率。
研究达格列净对 EF 不同范围的 CV 和非 CV 死亡率的影响。
设计、设置和参与者：这是一项对来自 Dapagliflozin 和预防心力衰竭不良结局（DAPA-HF）试验（参与者左心室 EF[LVEF]≤40%）和 Dapagliflozin 评价改善射血分数保留心力衰竭患者的生活（DELIVER）试验（参与者 LVEF>40%）的数据进行的参与者水平、汇总、预先指定的二次分析，以评估随机治疗对特定原因死亡率的影响。这些试验将慢性 HF、纽约心脏协会（NYHA）心功能 II-IV 级症状和升高的利钠肽的患者相邻分组，接受达格列净（10mg，每日一次）或安慰剂治疗。每项研究的主要终点是 HF 恶化事件（住院或紧急心衰就诊）或 CV 死亡的复合事件。包括所有死亡在内的临床结局由临床终点委员会根据治疗分配情况进行死因裁决。
达格列净与安慰剂。
根据基线 EF 检查死亡模式，使用 Cox 回归模型评估随机治疗对特定原因死亡的影响。使用泊松回归模型与连续 EF 建立关系。
在汇总数据集中的 11007 例患者中，随访期间有 1628 例死亡（平均[SD]年龄 71.7[10.3]岁；1139 例男性[70.0%]）。在死亡的患者中，872 例（53.5%）归因于 CV 死亡，487 例（29.9%）归因于非 CV 死亡，269 例（16.5%）归因于不明原因。在 CV 死亡中，289 例（33.1%；占总死亡人数的 17.8%）是由于 HF，441 例（50.6%；占总死亡人数的 27.1%）是猝死，69 例（7.9%；占总死亡人数的 4.2%）是由于中风，47 例（5.4%；占总死亡人数的 2.9%）是由于心肌梗死，26 例（3.0%；占总死亡人数的 1.6%）是由于其他 CV 原因。EF 较高的患者中非 CV 死亡的比例更高。在汇总人群中，EF 不同的患者中，达格列净治疗与较低的 CV 死亡率相关（风险比[HR]，0.86；95%CI，0.75-0.98；P=0.02），主要是由于猝死（HR，0.84；95%CI，0.70-1.01；P=0.07）和 HF 死亡（HR，0.88；95%CI，0.70-1.11；P=0.30）的发生率较低，而中风或 MI 死亡的发生率差异不大。
在 DAPA-HF 和 DELIVER 随机临床试验的 HF 患者的汇总分析中，EF 全范围内，达格列净显著降低了 CV 死亡风险，这得益于猝死和进展性 HF 死亡发生率的降低。
ClinicalTrials.gov 标识符：NCT03036124、NCT03619213。
