血栓弹力图评价抗血小板药物疗效对颅内外动脉支架术后再狭窄的影响

Efficacy of antiplatelet aggregation drugs in in-stent restenosis after intra-or extra-cerebral stent placement: evaluation by thrombelastogramy

摘要:

目的 分析血栓弹力图仪（TEG）检测颅内外动脉支架置入术（PTAS）后患者服用阿司匹林和氯吡格雷后血小板聚集的抑制率，了解其疗效对PTAS术后支架内再狭窄（ISR）的影响。方法 收集颅内外动脉PTAS术后因缺血性中风复发或者术后6～12个月常规行脑动脉数字减影血管造影（DSA）随访且行TEG检测的49例患者（64处病变血管）的临床资料。根据DSA结果分为ISR组和对照组（无ISR），比较两组间的各种血管病危险因素、血清超敏C反应蛋白（hs-CRP）水平、花生四烯酸（AA）途径和腺苷二磷酸（ADP）受体途径诱导血小板抑制率间的差异，探讨影响ISR形成的因素。结果 （1）卒中复发组与无复发组比较：复发组（男∶女＝1∶5）与无复发组（男∶女＝39∶4）组间性别组成的差异有统计学意义（P＜0.01）；复发组血清hs-CRP水平显著高于无复发组[（8.9±11.0） vs （2.9±4.1）mg/L，P＜0.05]；而其余各变量间差异均无统计学意义（P＞0.05）。（2）ISR组与对照组比较：ISR组患病年龄显著小于对照组[（58.0±12.8） vs （64.6±9.8）岁；P＜0.05]；两组间糖尿病患者的比例差异具有统计学意义（P＜0.05）；ISR组颅内外支架再狭窄比例（6/14 vs 8/14）与对照组（7/50 vs 43/50）间的差异有统计学意义（P＜0.05）；ISR组血清hs-CRP浓度显著高于对照组[（6.1±7.6） vs （2.1±2.1）mg/L，P＝0.028]；ISR组AA和ADP平均抑制率分别为（58.0±43.8）%和（28.1±26.1）%，显著低于对照组的（83.4±23.1）%和（52.8±29.5）%（均P＜0.01）。（3）Logistic回归分析显示，在校正了其他因素的影响后，仅ADP抑制率（氯吡格雷疗效）与ISR的形成呈负相关（HR＝0.959；95% CI 0.921～0.998；P＝0.039）。结论 氯吡格雷抗血小板聚集的疗效与ISR的形成呈负相关，即氯吡咯雷抵抗在ISR的形成中起非常重要的作用。

Abstract:

Objective To evaluate the efficacy of antiplatelet aggregation drugs (aspirin and clopridogrel) in in-stent restenosis (ISR) after percutaneous transluminal angioplasty and stenting (PTAS) by using thromboelastography (TEG) to assess the inhibitory rates of platelet aggregation. Methods Clinical data of 49 patients who were rehospitalizated in 6 to 12 months after PTAS for conventional re-evaluation by digital subtraction angiography (DSA) and TEG, and 6 patients with recurrent ischemic stroke (infarction or transient) after intra-or extra-cerebral stent placement in Jinling Hospital in November 2010 to May 2012 were collected. All patients were assessed the inhibitory rates of arachidonic acid (AA) pathway and adenosine diphosphate (ADP) receptor pathway in platelets by TEG. DSA confirmed 14 ISR among 64 lesion vessels treated with stents (ISR group). Potential variables for restenosis and the inhibitory rates of AA pathway and ADP receptor pathway in platelets were analyzed for any predictive power for the ISR with SPSS version 15.0. Results (1) There was significant difference in male-to-female ratio between recurrent stroke group (male/female∶1/5) and non-recurrence group (male/female: 39/4; P＜0.01). The serum concentrations of high-sensitivity C reactive protein (hs-CRP) in patients with recurrent stroke were higher than those without recurrence [(8.9±11.0) vs (2.9±4.1) mg/L, P＜0.05)]. The differences of other variables between recurrent and non-recurrent groups were not significant (P＞0.05). (2) Compared with non-ISR (control) group, variables in ISR group including age [(58.0±12.8) vs (64.6±9.8) years], the ratio of diabetes, and the ratio of lesion distributions in intra-and extra-cranial vessels (6/14 vs 7/14, 7/50 vs 43/50) were all significantly different (P＜0.05). Moreover, the serum concentration of hs-CRP was remarkably higher in ISR group than in non-ISR group [(6.1±7.6) vs (2.1±2.1) mg/L, P＝0.028]. Additionally, inhibitory rates of AA pathway and ADP receptor in patients with ISR were (58.0±43.8)% and (28.1±26.1)% whereas those in patients without ISR were (83.4±23.1)% and (52.8±29.5)% respectively, with significant difference (P＜0.01). (3) Logistic regression analysis showed that the inhibitory rate of ADP receptor or efficacy of clopidogrel (HR＝0.959; 95% CI 0.921～0.998; P＝0.039) was the only independent negative predictor for ISR after adjustment of the influence of other variables. Conclusion Despite the differences of several variables are significant including age, diabetes, distribution of lesion location, serum concentration of hs-CRP, and efficacy of aspirin and clopidogrel between ISR and non-ISR groups, only the inhibitory rate of ADP receptor in platelets or efficacy of clopidogrel is associated with decreased risk of ISR.