TY - JOUR
T1 - Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure
T2 - A meta-analysis of 34 randomized controlled trials
AU - Fernandes, Gilson C.
AU - Fernandes, Amanda
AU - Cardoso, Rhanderson
AU - Penalver, Jorge
AU - Knijnik, Leonardo
AU - Mitrani, Raul D.
AU - Myerburg, Robert J.
AU - Goldberger, Jeffrey J.
N1 - Funding Information:
Funding sources: The authors have no funding sources to disclose.
Publisher Copyright:
© 2021 Heart Rhythm Society
PY - 2021/7
Y1 - 2021/7
N2 - Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated. Objective: The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF. Methods: We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD). Results: We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53–67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69–0.95; P = .008) and the “SCD” component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54–0.97; P = .03) compared with control. There was no significant difference in incident VA or the “cardiac arrest” SCD component between groups. Conclusion: SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.
AB - Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated. Objective: The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF. Methods: We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD). Results: We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53–67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69–0.95; P = .008) and the “SCD” component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54–0.97; P = .03) compared with control. There was no significant difference in incident VA or the “cardiac arrest” SCD component between groups. Conclusion: SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.
KW - Atrial fibrillation
KW - Meta-analysis
KW - Sodium-glucose cotransporter 2 inhibitors
KW - Sudden cardiac death
KW - Ventricular arrhythmia
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U2 - 10.1016/j.hrthm.2021.03.028
DO - 10.1016/j.hrthm.2021.03.028
M3 - Article
C2 - 33757845
AN - SCOPUS:85104640590
VL - 18
SP - 1098
EP - 1105
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 7
ER -