Curtain James P, Docherty Kieran F, Jhund Pardeep S, Petrie Mark C, Inzucchi Silvio E, Køber Lars, Kosiborod Mikhail N, Martinez Felipe A, Ponikowski Piotr, Sabatine Marc S, Bengtsson Olof, Langkilde Anna Maria, Sjöstrand Mikaela, Solomon Scott D, McMurray John J V
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Scotland, UK.
Section of Endocrinology, Yale School of Medicine, New Haven, CT, USA.
Eur Heart J. 2021 Sep 21;42(36):3727-3738. doi: 10.1093/eurheartj/ehab560.
The aim of this study was to examine the effect of dapagliflozin on the incidence of ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF).
In a post hoc analysis of DAPA-HF, we examined serious adverse event reports related to ventricular arrhythmias or cardiac arrest, in addition to adjudicated sudden death. The effect of dapagliflozin, compared with placebo, on the composite of the first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death was examined using Cox proportional hazards models. A serious ventricular arrhythmia was reported in 115 (2.4%) of the 4744 patients in DAPA-HF (ventricular fibrillation in 15 patients, ventricular tachycardia in 86, 'other' ventricular arrhythmia/tachyarrhythmia in 12, and torsade de pointes in 2 patients). A total of 206 (41%) of the 500 cardiovascular deaths occurred suddenly. Eight patients survived resuscitation from cardiac arrest. Independent predictors of the composite outcome (first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest or sudden death), ranked by chi-square value, were log-transformed N-terminal pro-B-type natriuretic peptide, history of ventricular arrhythmia, left ventricular ejection fraction, systolic blood pressure, history of myocardial infarction, male sex, body mass index, serum sodium concentration, non-white race, treatment with dapagliflozin, and cardiac resynchronization therapy. Of participants assigned to dapagliflozin, 140/2373 patients (5.9%) experienced the composite outcome compared with 175/2371 patients (7.4%) in the placebo group [hazard ratio 0.79 (95% confidence interval 0.63-0.99), P = 0.037], and the effect was consistent across each of the components of the composite outcome.
Dapagliflozin reduced the risk of any serious ventricular arrhythmia, cardiac arrest, or sudden death when added to conventional therapy in patients with HFrEF.
ClinicalTrials.gov unique identifier: NCT03036124 (DAPA-HF).
本研究旨在探讨达格列净对射血分数降低的心力衰竭（HFrEF）患者室性心律失常和心源性猝死发生率的影响。
在对DAPA-HF研究的事后分析中，我们除了判定的心源性猝死外，还检查了与室性心律失常或心脏骤停相关的严重不良事件报告。使用Cox比例风险模型研究了达格列净与安慰剂相比，对首次发生任何严重室性心律失常、复苏成功的心脏骤停或心源性猝死这一复合终点的影响。在DAPA-HF研究的4744例患者中，有115例（2.4%）报告了严重室性心律失常（15例为心室颤动，86例为室性心动过速，12例为“其他”室性心律失常/快速心律失常，2例为尖端扭转型室性心动过速）。500例心血管死亡患者中共有206例（41%）为心源性猝死。8例患者心脏骤停复苏成功。按卡方值排序，复合终点（首次发生任何严重室性心律失常、复苏成功的心脏骤停或心源性猝死）的独立预测因素为对数转换后的N末端B型利钠肽原、室性心律失常病史、左心室射血分数、收缩压、心肌梗死病史、男性、体重指数、血清钠浓度、非白人种族、使用达格列净治疗以及心脏再同步治疗。在分配接受达格列净治疗的参与者中，140/2373例患者（5.9%）发生了复合终点事件，而安慰剂组为175/2371例患者（7.4%）[风险比0.79（95%置信区间0.63-0.99），P = 0.037]，且该效应在复合终点的各个组成部分中均一致。
在HFrEF患者的常规治疗中加用达格列净可降低任何严重室性心律失常、心脏骤停或心源性猝死的风险。
ClinicalTrials.gov唯一标识符：NCT03036124（DAPA-HF）。
