目的:动脉粥样硬化性心血管疾病仍然是全球主要的死亡原因,冠状动脉疾病代表其最普遍的表现。最近,一种新型的抗糖尿病药物,即钠-葡萄糖协同转运蛋白-2(SGLT2)抑制剂,据报道,2型糖尿病(DM)患者具有显着的心肾优势,即使在没有预先存在DM的个体中,它们也可以降低心肾风险。目前,没有证据表明这些药物在急性冠脉综合征(ACS)中的安全性和有效性,无论糖尿病状况如何。这篇综述旨在全面介绍有关SGLT2抑制剂在ACS中的潜在作用的临床前和临床证据。作为该患者人群的标准护理治疗的辅助手段,同时还讨论了潜在的短期和长期心血管益处。
方法:通过MEDLINE(通过PubMed)进行了文献检索,Cochrane中央控制试验登记册,和Scopus直到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),真实世界的研究,和荟萃分析。
结果:来自临床前模型的证据表明,SGLT2抑制剂的使用与迟钝的缺血再灌注损伤和减少的心肌梗死面积有关,特别是在之前的治疗之后。虽然随机对照试验和现实世界的数据暗示在急性缺血环境中的潜在益处,显示左心室收缩和舒张功能的改善,充血,和各种心脏代谢参数,如血糖,体重,还有血压,最近发表的DAPA-MI(Dapagliflozin在无糖尿病或心力衰竭的心肌梗死中的应用)试验未确定替代心血管终点的明显优势.在接受经皮冠状动脉介入治疗的ACS患者中,SGLT2抑制剂似乎在减少造影剂诱导的急性肾损伤事件方面具有益处。然而,有关其他安全问题的数据,如由于低血压而停止治疗,血容量不足,或者酮症酸中毒,目前有限。
结论:尽管在2型DM的普通人群中观察到了公认的心血管益处,最近,在其他患者组中,无论糖尿病状态如何,现有证据不支持在ACS中使用SGLT2抑制剂.这个有趣的研究问题的明确答案,这可能会扩大这种新型药物的治疗适应症,需要大规模,精心设计的RCT。
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.