Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigate...

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Main Authors: Miao Lin, Shiyu Zhang, Lu Zhang, Chengying Yang, Yang Luo, Yajin Peng, Xiaoqiu Tan, Qiang Wen, Xinrong Fan, Xianhong Ou
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Systematic Reviews
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Online Access:https://doi.org/10.1186/s13643-025-02766-7
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author Miao Lin
Shiyu Zhang
Lu Zhang
Chengying Yang
Yang Luo
Yajin Peng
Xiaoqiu Tan
Qiang Wen
Xinrong Fan
Xianhong Ou
author_facet Miao Lin
Shiyu Zhang
Lu Zhang
Chengying Yang
Yang Luo
Yajin Peng
Xiaoqiu Tan
Qiang Wen
Xinrong Fan
Xianhong Ou
author_sort Miao Lin
collection DOAJ
description Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigated. To assess the beneficial impact of SGLT2 inhibitors on VAs in patients at various stages of HF, a systematic review and meta-analysis of randomized controlled trials involving SGLT2 inhibitors in this patient population was performed. Methods A comprehensive search of the PubMed, Embase, Ovid, ProQuest, Scopus, and Cochrane databases was performed for clinical trials published up to November 21, 2024. The primary outcomes of interest were incidences of VAs and sudden cardiac death (SCD) between the groups receiving SGLT2 inhibitors and the control drugs. For the outcomes observed in the populations of the included trials and in specific subgroups, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled and meta-analysed across the analyses. Results A total of 23 randomized trials (22 placebo-controlled trials and 1 active-controlled trial) involving 74,380 patients (37,372 receiving SGLT2 inhibitors and 37,008 in the control group) were included. The analysed SGLT2 inhibitors included canagliflozin, dapagliflozin, empagliflozin, bexagliflozin, sotagliflozin, and ertugliflozin. The participants were non-advanced HF patients, including at-risk for HF, pre-HF, and symptomatic HF, with follow-up duration ranging from 12 to 296 weeks. Compared with the control, treatment with SGLT2 inhibitors was associated with significantly reduced risk of VAs (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74–0.98; P = 0.02) and SCD (RR 0.79, 95% CI 0.64–0.98; P = 0.03). Subgroup analyses indicated that longer follow-up (≥ 1 year) taking SGLT2 inhibitors can still reduce the risk of VAs (RR 0.79, 95% CI 0.65–0.96; P = 0.02) and SCD (RR 0.80, 95% CI 0.65–0.99; P = 0.04). Conclusion SGLT2 inhibitors have beneficial effects on lowering risks of VAs and SCD in patients with type 2 diabetes, cardiovascular diseases, heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mildly reduced ejection fraction (HFmrEF), with longer follow-up duration reinforcing these findings. However, future prospective trials are needed to verify the effects of SGLT2 inhibitors on VAs and SCD. Systematic review registration PROSPERO (CRD42024601914)
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spelling doaj-art-52b445c2353c4da4a27102b121e8c3072025-02-02T12:10:57ZengBMCSystematic Reviews2046-40532025-02-0114111210.1186/s13643-025-02766-7Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trialsMiao Lin0Shiyu Zhang1Lu Zhang2Chengying Yang3Yang Luo4Yajin Peng5Xiaoqiu Tan6Qiang Wen7Xinrong Fan8Xianhong Ou9Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityDepartment of Cardiology, The Affiliated Hospital of Southwest Medical UniversityDepartment of Cardiology, The Affiliated Hospital of Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Cardiology, The Affiliated Hospital of Southwest Medical UniversityKey Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical UniversityAbstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to lower the risk of re-hospitalization and cardiovascular mortality among heart failure (HF) patients. Nevertheless, the impact of these agents on ventricular arrhythmias (VAs) has not been thoroughly investigated. To assess the beneficial impact of SGLT2 inhibitors on VAs in patients at various stages of HF, a systematic review and meta-analysis of randomized controlled trials involving SGLT2 inhibitors in this patient population was performed. Methods A comprehensive search of the PubMed, Embase, Ovid, ProQuest, Scopus, and Cochrane databases was performed for clinical trials published up to November 21, 2024. The primary outcomes of interest were incidences of VAs and sudden cardiac death (SCD) between the groups receiving SGLT2 inhibitors and the control drugs. For the outcomes observed in the populations of the included trials and in specific subgroups, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled and meta-analysed across the analyses. Results A total of 23 randomized trials (22 placebo-controlled trials and 1 active-controlled trial) involving 74,380 patients (37,372 receiving SGLT2 inhibitors and 37,008 in the control group) were included. The analysed SGLT2 inhibitors included canagliflozin, dapagliflozin, empagliflozin, bexagliflozin, sotagliflozin, and ertugliflozin. The participants were non-advanced HF patients, including at-risk for HF, pre-HF, and symptomatic HF, with follow-up duration ranging from 12 to 296 weeks. Compared with the control, treatment with SGLT2 inhibitors was associated with significantly reduced risk of VAs (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74–0.98; P = 0.02) and SCD (RR 0.79, 95% CI 0.64–0.98; P = 0.03). Subgroup analyses indicated that longer follow-up (≥ 1 year) taking SGLT2 inhibitors can still reduce the risk of VAs (RR 0.79, 95% CI 0.65–0.96; P = 0.02) and SCD (RR 0.80, 95% CI 0.65–0.99; P = 0.04). Conclusion SGLT2 inhibitors have beneficial effects on lowering risks of VAs and SCD in patients with type 2 diabetes, cardiovascular diseases, heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with mildly reduced ejection fraction (HFmrEF), with longer follow-up duration reinforcing these findings. However, future prospective trials are needed to verify the effects of SGLT2 inhibitors on VAs and SCD. Systematic review registration PROSPERO (CRD42024601914)https://doi.org/10.1186/s13643-025-02766-7Heart failureSGLT2 inhibitorSudden cardiac deathVentricular arrhythmiasMeta-analysis
spellingShingle Miao Lin
Shiyu Zhang
Lu Zhang
Chengying Yang
Yang Luo
Yajin Peng
Xiaoqiu Tan
Qiang Wen
Xinrong Fan
Xianhong Ou
Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
Systematic Reviews
Heart failure
SGLT2 inhibitor
Sudden cardiac death
Ventricular arrhythmias
Meta-analysis
title Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
title_full Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
title_fullStr Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
title_full_unstemmed Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
title_short Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials
title_sort redefining outcomes of ventricular arrhythmia for sglt2 inhibitor medication in heart failure patients a meta analysis of randomized controlled trials
topic Heart failure
SGLT2 inhibitor
Sudden cardiac death
Ventricular arrhythmias
Meta-analysis
url https://doi.org/10.1186/s13643-025-02766-7
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