Floyd Christopher N, Ferro Albert
Department of Clinical Pharmacology, Cardiovascular Division, British Heart Foundation Centre of Research Excellence, King's College London, London, UK.
Prostaglandins Other Lipid Mediat. 2015 Jul;120:21-7. doi: 10.1016/j.prostaglandins.2015.03.011. Epub 2015 Apr 11.
Antiplatelet drugs are prescribed to patients with cardiovascular disease in order to reduce their risk of clinically important atherothrombotic events. However, a proportion of patients fail to appropriately respond to these drugs in a heterogeneous phenomenon known as 'antiplatelet drug resistance'. Individuals who are identified as being resistant have a higher cardiovascular risk, but currently there is no clinically validated approach to identify and treat these individuals. Large randomised control trials have attempted to personalise antiplatelet therapy based on platelet function testing, but these have failed to demonstrate improved clinical outcomes. An alternative approach to this non-specific assessment of platelet function is to consider whether antiplatelet therapy may be personalised based on the identification of molecular mechanisms that are known to confer resistance. Here we present molecular insights into the mechanisms for aspirin and clopidogrel resistance, with a discussion of their clinical implications.
抗血小板药物被开给心血管疾病患者，以降低他们发生具有临床重要意义的动脉粥样硬化血栓形成事件的风险。然而，一部分患者对这些药物没有适当反应，这是一种被称为“抗血小板药物抵抗”的异质性现象。被确定为有抵抗性的个体心血管风险更高，但目前尚无经过临床验证的方法来识别和治疗这些个体。大型随机对照试验试图根据血小板功能测试来实现抗血小板治疗的个性化，但这些试验未能证明临床结果得到改善。这种对血小板功能的非特异性评估的另一种方法是考虑是否可以基于已知赋予抵抗性的分子机制的识别来实现抗血小板治疗的个性化。在此，我们阐述了对阿司匹林和氯吡格雷抵抗机制的分子见解，并讨论了它们的临床意义。
