Association of SGLT2 Inhibitors With Risk of Atrial Fibrillation and Stroke in Patients With and Without Type 2 Diabetes: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Zheng, Rujie; Wang, Yue; Tang, Jiyu; Duan, Jie-Ying; Yuan, Ming-Yue; Zhang, Jinying

doi:10.1097/fjc.0000000000001183

Cited by 43 publications

(29 citation statements)

References 51 publications

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“…We observed that SGLT2i use was associated with a lower risk of incident AF compared with GLP-1RA use, consistent with the existing literature [ 31 ]. SGLT2i use was shown to be associated with lower risk of incident AF compared with placebo [ 7 ]. In contrast, results from both meta-analyses of randomized controlled trials and observational studies showed no significant benefits with GLP-1RA use on reducing incident AF compared with placebo [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding GLP-1RA, exploratory analysis of REWIND trial suggested that dulaglutide was associated with lower risk of ischemic stroke but neutral on hemorrhagic stroke compared with placebo [ 6 ]. Furthermore, SGLT2i was shown to be associated with lower risk of incident atrial fibrillation (AF) [ 7 ], but not for GLP-1RA [ 8 ]. Whether this may imply differential benefits on the risk of cardioembolic stroke between SGLT2i and GLP1-RA users remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong

Lui

Tang

et al. 2023

Cardiovasc Diabetol

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Background There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them. Methods A population-based, retrospective cohort of patients with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models. Results A total of 5840 patients (2920 SGLT2i users; 2920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months, there were 111 (1.9%) events of stroke (SGLT2i: 62, 2.1%; GLP-1RA: 49 1.7%). SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR 1.46, 95% CI 0.99–2.17, p = 0.058). SGLT2i users had higher risk of ischemic stroke (HR 1.53, 95% CI 1.01–2.33, p = 0.044) but similar risk of hemorrhagic stroke compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR 0.43, 95% CI 0.23–0.79, p = 0.006), risk of cardioembolic stroke was similar. Conclusions Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong

Lui

Tang

et al. 2023

Cardiovasc Diabetol

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“…21,22 A meta-analysis of existing RCTs suggests that SGLT2 inhibitors may indeed be associated with a lower risk of incident AF (odds ratio 0.82 [95% CI 0.72-0.93]; P = 0.002), consistent with our study. 23 While the potential antiarrhythmic mechanisms of SGLT2 inhibitors 11,24,25 should theoretically result in a reduction of both supraventricular and ventricular arrhythmias, the bulk of the evidence from RCTs suggests that SGLT2 inhibitors do not affect ventricular arrhythmias or sudden cardiac death. 26,27 In one meta-analysis, however, a significantly lower risk of VT was observed (relative risk 0.73 [95% CI 0.53-0.99]).…”

Section: Discussionmentioning

confidence: 99%

Incident heart failure, arrhythmias and cardiovascular outcomes with sodium‐glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes: Insights from a global federated electronic medical record database

Fawzy

Rivera‐Caravaca

Underhill³

et al. 2022

Diabetes Obesity Metabolism

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Aim To investigate the impact of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes. Methods All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity‐score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non‐SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all‐cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest. Results A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non‐SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68‐0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all‐cause mortality (HR 0.61, 95% CI 0.58‐0.64), cardiac arrest (HR 0.70, 95% CI 0.63‐0.78), incident AF (HR 0.81, 95% CI 0.76‐0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88‐0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88‐0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71‐0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88‐1.00). Conclusion Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.

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“…A recent metanalysis by Zheng et al included 20 randomized trials involving 63,604 patients, most of them with DM. The primary analysis evaluated the incidence of AF and stroke [ 78 ]. The SGLT2 inhibitors evaluated were dapagliflozin (seven studies, 28,834 patients), empagliflozin (five studies, 9082 patients), canagliflozin (seven studies, 17,440 patients), and ertugliflozin (one study, 8246 patients).…”

Section: Effect Of Sglt2 Inhibition In Atrial Fibrillation: Clinical ...mentioning

confidence: 99%

A New Hope: Sodium-Glucose Cotransporter-2 Inhibition to Prevent Atrial Fibrillation

Karamichalakis

Kolovos

Paraskevaidis

et al. 2022

JCDD

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Atrial arrhythmias are common in patients with diabetes mellitus (DM), and despite recent advances in pharmaceutical and invasive treatments, atrial fibrillation (AF) and atrial flutter (AFl) are still associated with substantial mortality and morbidity. Clinical trial data imply a protective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on the occurrence of AF and AFl. This review summarizes the state of knowledge regarding DM-mediated mechanisms responsible for AF genesis and recurrence but also discusses the recent data from experimental studies, published trials and metanalyses.

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Association of SGLT2 Inhibitors With Risk of Atrial Fibrillation and Stroke in Patients With and Without Type 2 Diabetes: A Systemic Review and Meta-Analysis of Randomized Controlled Trials

Abstract: Supplemental Digital Content is Available in the Text.

Cited by 43 publications

References 51 publications

Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong

Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong

Incident heart failure, arrhythmias and cardiovascular outcomes with sodium‐glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes: Insights from a global federated electronic medical record database

A New Hope: Sodium-Glucose Cotransporter-2 Inhibition to Prevent Atrial Fibrillation

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