Abstract
AimsThe 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).Methods and resultsIn 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.ConclusionsDapagliflozin reduced the risk of any serious ventricular arrhythmia, cardiac arrest, or sudden death when added to conventional therapy in patients with HFrEF.Clinical trial registration ClinicalTrials.gov unique identifier: NCT03036124 (DAPA-HF).
Highlights
One patient who had the same time to the occurrence of a serious ventricular arrhythmia and resuscitated cardiac arrest was counted as a resuscitated cardiac arrest in the analysis of the primary composite outcome
The main finding of this analysis was that dapagliflozin reduced the risk of the composite outcome of an investigator-reported serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death in patients with heart failure and reduced ejection fraction (HFrEF) (Graphical Abstract)
In DAPA-HF, ventricular arrhythmias were identified through adverse event reporting by investigators, rather than by systematic monitoring
Summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce both worsening heart failure and death from cardiovascular causes in patients with heart failure and reduced ejection fraction (HFrEF).[1,2,3,4] Ventricular arrhythmias are common and are one of the key causes of death in HFrEF, as indicated by the benefit of implantable cardioverter defibrillators (ICDs) on sudden death.[5,6,7,8,9] rates of sudden death have been declining over the past three decades with improving pharmacological therapy, this mode of death remains the principal cause of mortality in ambulatory patients with HFrEF, those with mild symptoms.[10]It is important, to investigate the effect of new therapies for HFrEF on ventricular arrhythmias and mode of death, including sudden death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce both worsening heart failure and death from cardiovascular causes in patients with heart failure and reduced ejection fraction (HFrEF).[1,2,3,4] Ventricular arrhythmias are common and are one of the key causes of death in HFrEF, as indicated by the benefit of implantable cardioverter defibrillators (ICDs) on sudden death.[5,6,7,8,9] rates of sudden death have been declining over the past three decades with improving pharmacological therapy, this mode of death remains the principal cause of mortality in ambulatory patients with HFrEF, those with mild symptoms.[10]. Potential antiarrhythmic actions include favourable effects on left ventricular loading conditions and remodelling, autonomic nervous system activity, serum electrolytes, the cardiac sodium channel current (late /Na), and the myocardial sodiumhydrogen (Naþ/Hþ) exchanger.[11,12,13,14,15,16,17,18,19]
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