Gaertner Sébastien, Cordeanu Eléna-Mihaela, Nouri Salah, Mirea Corina, Stephan Dominique
Department of Hypertension, Vascular Disease and Clinical Pharmacology, Strasbourg Regional University Hospital, 1, place de l'Hôpital, BP 426, 67091 Strasbourg, France.
Department of Hypertension, Vascular Disease and Clinical Pharmacology, Strasbourg Regional University Hospital, 1, place de l'Hôpital, BP 426, 67091 Strasbourg, France.
Arch Cardiovasc Dis. 2016 Mar;109(3):216-22. doi: 10.1016/j.acvd.2015.11.007. Epub 2016 Jan 14.
The pleiotropic effects of statins, beyond their cholesterol-lowering properties, are much debated. In primary prevention, several observational cohort and case-control studies appear to show that statins reduce the incidence of venous thromboembolism by about 30%. In a single randomized placebo-controlled clinical trial (JUPITER), which included 17,000 patients, rosuvastatin 20mg/day reduced the risk of venous thromboembolism by 43%. However, these patients were at low risk of venous thromboembolism, and the frequency of the event was, in principle, low. In secondary prevention, several observational studies and post-hoc analyses of randomized clinical trials have suggested that statins may prevent recurrence of venous thromboembolism. However, none of these studies had enough scientific weight to form the basis of a recommendation to use statins for secondary prevention. The putative preventive effect of statins appears to be independent of plasma cholesterol concentration and could be a pharmacological property of the statin class, although a dose-effect relationship has not been demonstrated. The mechanism through which statins might prevent venous thrombosis is thought to involve their anti-inflammatory and antioxidant effects or perhaps a more specific action, by blocking the degradation of antithrombotic proteins. A mechanism involving the action of statins on interactions between risk factors for atherosclerosis and venous thromboembolism is supported by some studies, but not all. In the absence of firm evidence, statins cannot currently be recommended for primary or secondary prevention of venous thromboembolism.
他汀类药物除了具有降低胆固醇的特性外,其多效性作用备受争议。在一级预防中,多项观察性队列研究和病例对照研究似乎表明,他汀类药物可使静脉血栓栓塞的发生率降低约30%。在一项纳入了17000名患者的单中心随机安慰剂对照临床试验(JUPITER)中,每天服用20mg瑞舒伐他汀可使静脉血栓栓塞风险降低43%。然而,这些患者发生静脉血栓栓塞的风险较低,且该事件的发生率原则上也较低。在二级预防中,多项观察性研究以及随机临床试验的事后分析表明,他汀类药物可能预防静脉血栓栓塞的复发。然而,这些研究均没有足够的科学依据来形成使用他汀类药物进行二级预防的推荐基础。他汀类药物假定的预防作用似乎独立于血浆胆固醇浓度,可能是他汀类药物类别的药理学特性,尽管尚未证实存在剂量效应关系。他汀类药物预防静脉血栓形成的机制被认为涉及其抗炎和抗氧化作用,或者可能是通过阻断抗血栓蛋白的降解而产生更具特异性的作用。一些研究支持他汀类药物作用于动脉粥样硬化和静脉血栓栓塞危险因素之间相互作用的机制,但并非所有研究都支持。在缺乏确凿证据的情况下,目前不能推荐使用他汀类药物进行静脉血栓栓塞的一级或二级预防。