Effects of Combined Therapy with SGLT2i and GLP-1RAs on Atrial Fibrillation Recurrence After Catheter Ablation in Diabetic Cohorts: One-Year Outcomes from Continuous Monitoring
Abstract
To evaluate the effect of sodium–glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and their combination on atrial fibrillation (AF) recurrence after catheter ablation in patients with type 2 diabetes mellitus (T2DM). In a prospective cohort study, patients with T2DM undergoing AF ablation were stratified into three groups: SGLT2i-users, GLP-1RAs-users, and combined SGLT2i/GLP-1RAs users. Diabetics under SGLT2i/GLP-1RAs therapy had worse glycemic control (HbA1c > 7%). AF recurrence was assessed over 12 months using implantable continuous monitoring (ICM). Secondary outcomes included the inflammatory/oxidative stress markers measured at the 12-month follow-up. At the follow-up end, patients treated with SGLT2i/GLP-1RAs versus monotherapy patients showed significantly lower AF recurrence and serum inflammatory/oxidative stress markers, despite having higher HbA1c levels (p < 0.05). Combined SGLT2i/GLP-1RAs therapy reduced AF recurrence following catheter ablation and inflammatory/oxidative stress in T2DM patients.
Introduction
Type 2 diabetes mellitus (T2DM) and worse glycemic control could increase atrial fibrillation (AF) recurrence post-catheter ablation [1]. Hyperglycemia and elevated levels of hemoglobin A1c (HbA1c) are both strongly associated with an increased rate of AF recurrence post-ablation in T2DM patients, via over-inflammation/oxidative stress [2]. In this context, new anti-T2DM therapies, as the sodium–glucose-transporter 2 inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), have been safely used to reduce AF recurrence post-catheter ablation in T2DM cohorts [3,4]. Intriguingly, SGLT2i could reduce AF recurrence after catheter ablation via anti-inflammatory/oxidative effects and favoring the myocardial substrate modulation [5]. These effects are linked to the amelioration of cardiac electrophysiological properties in T2DM patients and lead to the best clinical outcomes [5]. Similarly, GLP-1 RAs reduce the AF recurrence following ablation via anti-inflammatory/oxidative effects and significant weight loss [4,6]. Therefore, assuming the over-inflammation/oxidative stress and the worse glycemic control as the main causes of AF recurrence post ablative approach, we might speculate that adding the SGLT2i to chronic therapy with GLP-1RAs in patients with worse glycemic control (Hb1Ac > 7 mg/dl) might result in the amelioration of glycemic control, and then in the significant reduction in inflammatory/oxidative stress in these patients. These effects could consequently reduce the AF recurrence post-ablation. On the other hand, we have no conclusive data about the effects played by SGLT2i added to GLP-1RAs on the AF recurrence post-ablation in T2DM patients, and particularly in those with over-inflammation/oxidative stress and worse glycemic control. Furthermore, in the current study, we investigated the relationship between glycemic control, inflammatory/oxidative stress, and AF recurrence after ablation in T2DM patients divided into patients under SGLT2i therapy (SGLT2i-users) vs. patients under GLP-1RAs therapy (GLP-1RAs-users) vs. patients under combined therapy with SGLT2i and GLP-1RAs (GLP-1RAs/SGLT2i-users). The AF recurrence post-catheter ablation was evaluated at 1 year of follow-up by implantable continuous monitoring (ICM) devices. Secondly, we evaluated the inflammatory/oxidative stress burden in the three study cohorts of T2DM patients at the follow-up end.
Results
At 1 year, the combination therapy group had significantly higher CRT-response rate (66.3 %) compared to SGLT2i (59.6 %) and GLP-1RAs (59.2 %) groups (p = 0.014), and lower HF-hospitalization rates (15.7 % vs. 23.5 % and 24.4 %, respectively; p = 0.001). Multivariate Cox analysis confirmed combination therapy as an independent predictor of CRT response (HR 1.659, CI 95 % [1.320–2.085]; p 0.001) and reduced HF hospitalizations (0.822, CI 95 % [0.751–0.966]; p0.012) at 1 year of follow-up.
Conclusions
Combined therapy with SGLT2i and GLP-1RAs could reduce about 56% the AF recurrence at 1 year of follow-up post-catheter ablation. These effects are linked to the significant reduction in inflammatory cellular and molecular markers despite worse periprocedural and follow-up term glycemic control. The anti-inflammatory and cardioprotective properties (reduction in AF recurrence) could be due to the synergistic anti-inflammatory and cardioprotective effect of SGLT2i [9,10,11] added to GLP-1RAs therapy [12] in T2DM with paroxysmal AF undergoing catheter ablation, beyond glycemic control. These synergistic effects played by SGLT2i and GLP-1RAs could improve post-ablation outcomes in high-risk diabetic patients. Further randomized trials are warranted to confirm these observations and explore the mechanistic pathways underlying this therapeutic benefit.
Autori
by Celestino Sardu 1,2,*ORCID andRaffaele Marfella 1,2ORCID
Articolo Completo
Prof. Dott. Celestino Sardu
Cardiologo
Il Prof. Dottor Celestino Sardu Cardiologo, dal momento della sua presa in servizio, ha svolto attività di ricerca presso cattedra di Medicina Interna dell’Università della Campania “Luigi Vanvitelli” e in collaborazione con Centri esteri degli Stati Uniti d’ America (Tample University, Philadelphia; A. Einstein College of Medicine, NYC; Stanford University, Paolo Alto; USA)