Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
Clin Ther. 2024 Nov;46(11):841-850. doi: 10.1016/j.clinthera.2024.06.010. Epub 2024 Jul 10.
Atherosclerotic cardiovascular disease remains a prominent global cause of mortality, with coronary artery disease representing its most prevalent manifestation. Recently, a novel class of antidiabetic medication, namely sodium-glucose cotransporter-2 (SGLT2) inhibitors, has been reported to have remarkable cardiorenal advantages for individuals with type 2 diabetes mellitus (DM), and they may reduce cardiorenal risk even in individuals without pre-existing DM. Currently, there is no evidence regarding the safety and efficacy of these drugs in acute coronary syndrome (ACS), regardless of diabetes status. This review aims to comprehensively present the available preclinical and clinical evidence regarding the potential role of SGLT2 inhibitors in the context of ACS, as adjuncts to standard-of-care treatment for this patient population, while also discussing potential short- and long-term cardiovascular benefits.
A literature search was performed through MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Scopus until February 26, 2024. Eligible were preclinical and clinical studies, comprising randomized controlled trials (RCTs), real-world studies, and meta-analyses.
Evidence from preclinical models indicates that the use of SGLT2 inhibitors is associated with a blunted ischemia-reperfusion injury and decreased myocardial infarct size, particularly after prior treatment. Although RCTs and real-world data hint at a potential benefit in acute ischemic settings, showing improvements in left ventricular systolic and diastolic function, decongestion, and various cardiometabolic parameters such as glycemia,body weight, and blood pressure, the recently published DAPA-MI (Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure) trial did not establish a clear advantage regarding surrogate cardiovascular end points of interest. SGLT2 inhibitors appear to provide a benefit in reducing contrast-induced acute kidney injury events in patients with ACS undergoing percutaneous coronary intervention. However, data on other safety concerns, such as treatment discontinuation because of hypotension, hypovolemia, or ketoacidosis, are currently limited.
Despite the well-established cardiovascular benefits observed in the general population with type 2 DM and, more recently, in other patient groups irrespective of diabetes status, existing evidence does not support the use of SGLT2 inhibitors in the context of ACS. Definitive answers to this intriguing research question, which could potentially expand the therapeutic indications of this novel drug class, require large-scale, well-designed RCTs.
动脉粥样硬化性心血管疾病仍然是全球主要的死亡原因，其中冠状动脉疾病是最常见的表现形式。最近，一类新型的抗糖尿病药物，即钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂，已被报道对 2 型糖尿病（DM）患者具有显著的心肾优势，并且即使在没有预先存在的 DM 的患者中，它们也可能降低心肾风险。目前，无论糖尿病状况如何，这些药物在急性冠状动脉综合征（ACS）中的安全性和疗效都没有证据。本综述旨在全面介绍 SGLT2 抑制剂在 ACS 背景下作为该患者群体标准治疗辅助的潜在作用的现有临床前和临床证据，同时讨论潜在的短期和长期心血管获益。
通过 MEDLINE（通过 PubMed）、Cochrane 对照试验中心注册库和 Scopus 进行文献检索，检索时间截至 2024 年 2 月 26 日。符合条件的是临床前和临床研究，包括随机对照试验（RCT）、真实世界研究和荟萃分析。
临床前模型的证据表明，使用 SGLT2 抑制剂与缺血再灌注损伤减轻和心肌梗死面积减小相关，特别是在预先治疗后。尽管 RCT 和真实世界数据提示在急性缺血环境中可能有潜在获益，显示左心室收缩和舒张功能、充血以及各种心脏代谢参数（如血糖、体重和血压）的改善，但最近发表的 DAPA-MI（无糖尿病或心力衰竭的达格列净治疗心肌梗死）试验并未在感兴趣的替代心血管终点方面确立明确优势。SGLT2 抑制剂似乎在降低接受经皮冠状动脉介入治疗的 ACS 患者的对比剂诱导的急性肾损伤事件方面提供了获益。然而，目前关于其他安全性问题的数据，如因低血压、低血容量或酮症酸中毒而停药的数据有限。
尽管在 2 型 DM 患者以及最近在其他无论糖尿病状况如何的患者群体中观察到了明确的心血管获益，但现有证据不支持在 ACS 背景下使用 SGLT2 抑制剂。这个有趣的研究问题的明确答案，可能会扩大这一新药类别的治疗适应症，需要大规模、精心设计的 RCT。
