Geisler Tobias, Zürn Christine, Paterok Maria, Göhring-Frischholz Katrin, Bigalke Boris, Stellos Konstantinos, Seizer Peter, Kraemer Bjoern F, Dippon Jürgen, May Andreas E, Herdeg Christian, Gawaz Meinrad
Medizinische Klinik III, University Hospital Tübingen, Otfried-Müller-Strasse 10 72076, Tübingen, Germany.
Eur Heart J. 2008 Jul;29(13):1635-43. doi: 10.1093/eurheartj/ehn212. Epub 2008 May 24.
There are growing data suggesting a clinical relevance of residual platelet aggregation (RPA) in patients undergoing PCI. Drug-drug interaction of statins and clopidogrel has been controversially discussed in ex vivo studies and clinical trials. The aim of the present study was to investigate the effects of peri-procedural statin medication on the metabolization of aspirin and clopidogrel with regard to platelet aggregation and clinical outcome in patients undergoing coronary intervention.
Patients with coronary stenting for symptomatic coronary artery disease are routinely evaluated by platelet function analysis in a monocentre registry, and for the present study, a consecutive cohort of 1155 patients were analysed. About 87.7% of the patients were treated with statins at the time of platelet function analysis. Residual platelet activity assessed by adenosine diphosphate (20 micromol/L)-induced platelet aggregation was not significantly influenced by statin treatment. Nor the significant effects of CYP3A4-metabolization pathway on post-treatment aggregation were recorded, although there was even a trend to lower RPA values in patients treated with CYP3A4-metabolized statins. Further, in an inter-individual analysis comparing patients treated with CYP3A4- and non-CYP3A4-metabolized statins, no time-dependent difference of clopidogreĺs anti-aggregatory effects was observed. Clinical follow-up of major adverse events (myocardial infarction, ischaemic stroke, death) in 991 patients within 3 months revealed no significant adverse effects of statin treatment on clinical outcome. Instead, statin treatment was independently associated with lower incidence of composite events (HR 0.44, 95% confidence interval 0.23-0.83, P = 0.01).
Peri-procedural co-administration of statins does not increase the post-interventional RPA in cardiovascular patients treated with dual antiplatelet therapy and does not worsen the clinical prognosis of these patients.
越来越多的数据表明，残余血小板聚集（RPA）在接受经皮冠状动脉介入治疗（PCI）的患者中具有临床相关性。他汀类药物与氯吡格雷的药物相互作用在体外研究和临床试验中一直存在争议。本研究的目的是探讨围手术期他汀类药物治疗对阿司匹林和氯吡格雷代谢的影响，以及对接受冠状动脉介入治疗患者血小板聚集和临床结局的影响。
在一个单中心登记处，对有症状冠状动脉疾病的冠状动脉支架置入患者进行血小板功能分析，作为常规评估。在本研究中，对连续的1155例患者进行了分析。在进行血小板功能分析时，约87.7%的患者接受了他汀类药物治疗。用二磷酸腺苷（20微摩尔/升）诱导的血小板聚集评估的残余血小板活性不受他汀类药物治疗的显著影响。虽然使用CYP3A4代谢的他汀类药物治疗的患者的RPA值甚至有降低的趋势，但也未记录到CYP3A4代谢途径对治疗后聚集的显著影响。此外，在一项个体间分析中，比较使用CYP3A4代谢和非CYP3A4代谢的他汀类药物治疗的患者，未观察到氯吡格雷抗聚集作用的时间依赖性差异。对991例患者在3个月内的主要不良事件（心肌梗死、缺血性中风、死亡）进行临床随访，结果显示他汀类药物治疗对临床结局无显著不良影响。相反，他汀类药物治疗与复合事件发生率较低独立相关（风险比0.44，95%置信区间0.23 - 0.83，P = 0.01）。
在接受双重抗血小板治疗的心血管疾病患者中，围手术期联合使用他汀类药物不会增加介入治疗后的RPA，也不会使这些患者的临床预后恶化。
