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Abstract Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I2 = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I2 = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I2 = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality. Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I2). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus.

IntroductionThe Watchman FLX is a novel device for transcatheter left atrial appendage occlusion (LAAO) specifically designed to improve procedural performance in more complex anatomies with a better safety profile. Recently, small prospective non-randomized studies have shown good procedural success and safety compared with previous experiences. Results from large multicenter registries are needed to confirm the safety and efficacy of the Watchman FLX device in a real-world setting.MethodsItalian FLX registry is a retrospective, non-randomized, multicentric study across 25 investigational centers in Italy including consecutive patients undergoing LAAO with the Watchman FLX between March 2019 and September 2021 (N = 772). The primary efficacy outcome was the technical success of the LAAO procedure (peri-device flow ≤ 5 mm) as assessed by intra-procedural imaging. The peri-procedural safety outcome was defined as the occurrence of one of the following events within 7 days after the procedure or by hospital discharge: death, stroke, transient ischemic attack, major extracranial bleeding (BARC type 3 or 5), pericardial effusion with tamponade or device embolization.ResultsA total of 772 patients were enrolled. The mean age was 76 ± 8 with a mean CHA2DS2-VASc score of 4.1 ± 1.4 and a mean HAS-BLED score of 3.7 ± 1.1. Technical success was achieved in 772 (100%) patients with the first device implanted in 760 (98.4%) patients. A peri-procedural safety outcome event occurred in 21 patients (2.7%) with major extracranial bleeding being the most common (1.7%). No device embolization occurred. At discharge 459 patients (59.4%) were treated with dual antiplatelet therapy (DAPT).ConclusionsThe Italian FLX registry represents the largest multicenter retrospective real-world study reporting periprocedural outcome of LAAO with the Watchman FLX device, resulting in a procedural success rate of 100% and a low incidence of peri-procedural major adverse events (2.7%).