Fedele Damiano, Casuso Alvarez Marcello, Maida Angelo, Vasumini Nicolò, Amicone Sara, Canton Lisa, Di Leo Michele, Basile Marco, Manaresi Tommaso, Angeli Francesco, Armillotta Matteo, Bergamaschi Luca, Pizzi Carmine
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum, University of Bologna, Via Zamboni, 33, Bologna 40126, Italy.
Cardiovascular Division, Morgagni-Pierantoni University Hospital, Via Carlo Forlanini, 34, Forlì 47121, Italy.
Eur Heart J Cardiovasc Pharmacother. 2025 Aug 12;11(5):441-450. doi: 10.1093/ehjcvp/pvaf040.
The ability of sodium-glucose co-transporter 2 (SGLT2) inhibitors to prevent atrial fibrillation (AF) has been evaluated in various studies with conflicting results. This study aimed to determine whether SGLT2 inhibitors have a protective effect against AF depending on the baseline clinical condition in which the randomized controlled trials (RCTs) were conducted.
A trial-level meta-analysis was performed including 52 RCTs (112 031 patients) comparing SGLT2 inhibitors with placebo and reporting the number of patients who developed AF in each arm. Risk ratios (RRs) for AF development with 95% confidence intervals (95% CIs) were pooled using a random-effects model. Subgroup analyses were performed by classifying RCTs according to the inclusion criteria of each trial [diabetes, chronic kidney disease, heart failure with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF)]. Overall, SGLT2 inhibitors prevented AF (RR = 0.86, 95% CI 0.77-0.96). In the subgroup analysis, the AF-preventive ability of SGLT2 inhibitors was influenced by HF, being preserved in RCTs recruiting 9141 patients with HFrEF, but not in those recruiting 12 877 subjects with HFmrEF/HFpEF (P-value for group difference = 0.01). Meta-regression showed a reduced efficacy of SGLT2 inhibitors in preventing AF when more patients with hypertension or higher EF were enrolled (P < 0.01 for both).
Sodium-glucose co-transporter 2 inhibitors prevent AF. Their protective effect was confirmed in the HFrEF subgroup, but not in RCTs recruiting patients with HFmrEF/HFpEF, possibly indicating a different pathophysiology leading to AF among these conditions. However, given the limitations of a trial-level analysis, these findings are exploratory, pending confirmation from patient-level data.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂预防心房颤动（AF）的能力已在多项研究中进行评估，但结果相互矛盾。本研究旨在确定SGLT2抑制剂是否根据进行随机对照试验（RCT）时的基线临床状况对AF具有保护作用。
进行了一项试验水平的荟萃分析，纳入52项RCT（112031例患者），比较SGLT2抑制剂与安慰剂，并报告每组发生AF的患者数量。使用随机效应模型汇总AF发生的风险比（RR）及95%置信区间（95%CI）。根据每个试验的纳入标准[糖尿病、慢性肾脏病、射血分数降低的心力衰竭（HFrEF）、轻度射血分数降低（HFmrEF）和射血分数保留（HFpEF）]对RCT进行分类，进行亚组分析。总体而言，SGLT2抑制剂可预防AF（RR = 0.86，95%CI 0.77 - 0.96）。在亚组分析中，SGLT2抑制剂预防AF的能力受心力衰竭影响，在招募9141例HFrEF患者的RCT中具有保护作用，但在招募12877例HFmrEF/HFpEF受试者的RCT中则不然（组间差异P值 = 0.01）。荟萃回归显示，当纳入更多高血压患者或更高射血分数的患者时，SGLT2抑制剂预防AF的疗效降低（两者P均 < 0.01）。
钠-葡萄糖协同转运蛋白2抑制剂可预防AF。其保护作用在HFrEF亚组中得到证实，但在招募HFmrEF/HFpEF患者的RCT中未得到证实，这可能表明这些情况下导致AF的病理生理学不同。然而，鉴于试验水平分析的局限性，这些发现具有探索性，有待患者水平数据的证实。
