Chapman M John
National Institute for Health and Medical Research (INSERM), Unité 551, Dyslipoprotéinemies et Athérosclérose: Génétique, Métabolisme et Thérapeutique, Hôpital de la Pitié, 75651-Paris Cedex 13, France.
Pharmacol Ther. 2007 Jan;113(1):184-96. doi: 10.1016/j.pharmthera.2006.08.005. Epub 2006 Sep 15.
Atherothrombosis results from direct interaction between the atherosclerotic plaque and arterial thrombosis, and underlies most forms of cardiovascular disease (CVD). The pathophysiology of atherosclerosis is now recognised to involve endothelial dysfunction and dyslipidemia with cholesterol accumulation, as well as critical immuno-inflammatory and apoptotic dimensions. Erosion or rupture of a vulnerable, lipid-rich, inflammatory atherosclerotic plaque triggers the formation of a platelet-rich thrombus that may partially or completely occlude the artery, with resultant clinical scenarios including stable and unstable angina, acute myocardial infarction (MI) and ischaemic stroke. Insight into the pathophysiology of atherothrombosis indicates that an integrated risk factor approach, focusing particularly on management of dyslipidaemia (with a statin) and thrombosis (with aspirin), may constitute an optimal therapeutic approach. Both agents have established roles in secondary prevention. Statin action on atherogenic lipoproteins mediates plaque stabilisation, modification of plaque morphology and attenuation of inflammation, and may lead to plaque regression, while aspirin reduces platelet activation and aggregation, decreases release of inflammatory cytokines at sites of vascular injury and attenuates vasoconstriction. Given these complementary modes of action, this combination would be a logical choice for reducing atherothrombotic risk in patients with CVD. Meta-analysis of 5 major clinical studies has demonstrated that the combination of pravastatin plus aspirin was significantly more effective than either agent alone in reducing the relative risk of key cardiovascular endpoints including MI and ischaemic stroke. This combination may therefore represent an important, cost-efficient therapeutic approach to reduction of cardiovascular risk and prevention of recurrent events in stable CVD.
动脉粥样硬化血栓形成是动脉粥样硬化斑块与动脉血栓直接相互作用的结果，是大多数心血管疾病（CVD）的基础。现在人们认识到动脉粥样硬化的病理生理学涉及内皮功能障碍、伴有胆固醇积聚的血脂异常，以及关键的免疫炎症和细胞凋亡方面。易损的、富含脂质的、炎症性动脉粥样硬化斑块的糜烂或破裂会触发富含血小板的血栓形成，该血栓可能部分或完全阻塞动脉，导致的临床情况包括稳定型和不稳定型心绞痛、急性心肌梗死（MI）和缺血性中风。对动脉粥样硬化血栓形成病理生理学的深入了解表明，一种综合的危险因素方法，尤其侧重于血脂异常（使用他汀类药物）和血栓形成（使用阿司匹林）的管理，可能构成一种最佳治疗方法。这两种药物在二级预防中都已确立了作用。他汀类药物对致动脉粥样硬化脂蛋白的作用介导斑块稳定、斑块形态改变和炎症减轻，并可能导致斑块消退，而阿司匹林可减少血小板活化和聚集，减少血管损伤部位炎症细胞因子的释放，并减轻血管收缩。鉴于这些互补的作用方式，这种联合用药将是降低CVD患者动脉粥样硬化血栓形成风险的合理选择。对5项主要临床研究的荟萃分析表明，普伐他汀加阿司匹林的联合用药在降低包括MI和缺血性中风在内的关键心血管终点的相对风险方面，比单独使用任何一种药物都显著更有效。因此，这种联合用药可能代表一种重要的、具有成本效益的治疗方法，用于降低心血管风险和预防稳定型CVD的复发事件。
