Institute of Cardiology, Jagiellonian University School of Medicine, Kraków, Poland; John Paul II Hospital, Kraków, Poland.
Pol Arch Intern Med. 2022 Feb 28;132(2). doi: 10.20452/pamw.16208.
Statins, 3‑hydroxy‑methylglutaryl coenzyme A reductase inhibitors, reduce the rate of cardiovascular events in primary and secondary prevention, and represent a cornerstone in the management of atherosclerotic vascular disease. Statins were also shown to be effective in lowering the risk of venous thromboembolism (VTE) in its primary and secondary prevention, but their use in VTE prophylaxis is still not approved and recommended in current guidelines. Several antithrombotic mechanisms of these cholesterol‑lowering agents, largely independent of the magnitude of low‑ density lipoprotein cholesterol reduction, were demonstrated in a broad spectrum of experimental in vitro and in vivo models. However, these studies yielded inconsistent results, such as substantial differences related to the use of specific statins, their dose or final concentration, and even the clinical setting (patients with cardiovascular disease or VTE vs healthy subjects). Anticoagulant properties of statins, reported for the first time 25 years ago, involve downregulation of tissue factor expression with a subsequent decreased thrombin generation and inhibition of thrombin‑mediated reactions, including factor V and factor XIII activation, and enhanced endothelial thrombomodulin expression resulting in increased protein C activation. Enhanced fibrinolysis was also reported partly as a result of reduced activity of fibrinolysis inhibitors such as plasminogen activator inhibitor‑1 (PAI‑1) and thrombin‑activatable fibrinolysis inhibitor. This review summarizes the findings of the studies from the 1990s until the most recent reports to update our knowledge on the impact of statins on blood coagulation and its potential clinical relevance.
他汀类药物，即 3-羟甲基戊二酰辅酶 A 还原酶抑制剂，可降低一级和二级预防中的心血管事件发生率，是动脉粥样硬化性血管疾病治疗的基石。他汀类药物在一级和二级预防中降低静脉血栓栓塞症（VTE）风险也已得到证实，但目前的指南并不推荐也不批准将其用于 VTE 预防。这些降脂药物具有多种抗血栓形成机制，在广泛的体外和体内实验模型中，这些机制在很大程度上独立于低密度脂蛋白胆固醇降低的幅度。然而，这些研究结果并不一致，例如与使用特定他汀类药物、剂量或最终浓度甚至临床环境（心血管疾病或 VTE 患者与健康受试者）有关的实质性差异。25 年前首次报道了他汀类药物的抗凝特性，涉及组织因子表达下调，随后凝血酶生成减少，以及抑制凝血酶介导的反应，包括因子 V 和因子 XIII 的激活，增强内皮血栓调节蛋白表达，从而增加蛋白 C 的激活。部分增强的纤溶也被报道是由于纤溶抑制剂如纤溶酶原激活物抑制剂-1（PAI-1）和凝血酶激活的纤溶抑制剂活性降低所致。本综述总结了 20 世纪 90 年代至最近报告的研究结果，更新了我们对他汀类药物对血液凝固的影响及其潜在临床意义的认识。
