We sought to assess the incidence of aspirin resistance after off-pump coronary artery bypass(OPCAB) surgery,and investigate whether clopidogrel can improve aspirin response and be safely applied early after OPCAB surgery.Sixty patients who underwent standard OPCAB surgery were randomized into two groups.One group(30 patients)received mono-antiplatelet treatment(MAPT) with aspirin 100 mg daily and the other group received dual antiplatelet treatment(DAPT) with aspirin 100 mg daily plus clopidogrel 75 mg daily.Platelet aggregations in response to arachidonic acid(PL_(AA)) and adenosine diphosphate(ADP)(PL_(ADP)) were measured preoperatively and on days 1 to 6,8 and10 after the antiplatelet agents were administered.A PL_(AA) level above 20%was defined as aspirin resistance.Postoperative bleeding and other perioperative variables were also recorded.There were no significant differences between the two groups in baseline characteristics,average number of distal anastomosis,operation time,postoperative bleeding,ventilation time and postoperative hospital stay.However,the incidence of aspirin resistance was significantly lower in the DAPT group than that in the MAPT group on the first and second day after antiplatelet agents were given(62.1%vs.32.1%,34.5%vs.10.7%,respectively,both P < 0.05).There was no significant difference in postoperative complication between the two groups.DAPT with aspirin and clopidogrel can be safely applied to OPCAB patients early after the procedure.Moreover,clopidogrel reduces the incidence of OPCAB-related aspirin resistance.
Xuezhong WangXiaoxuan GongTiantian ZhuQiu ZhangYangyang ZhangXiaowei WangZhijian YangChunjian Lia
Clopidogrel is a pro-drug which needs two-step metabolism to produce the active thiol metabolite.This study aimed to explore an efficient method to simultaneously determine the plasma clopidogrel,2-oxo-clopidogrel(2-Oxo-CLP),and the clopidogrel active metabolite(CAM).A high-throughput liquid chromatography tandem mass spectrometry(LC-MS/MS)was therefore developed.The analytes were extracted from plasma by using methyl tert-butyl ether(MTBE).Chromatographic separation was performed on a C18 column under an isocratic elution,accompanied with acetonitrile and deionized water containing 0.1%formic acid.After optimizing the condition of LC-MS/MS,a stable linearity was observed in the standard curves over the concentration ranges of 0.05 to 50.0 ng/mL for clopidogrel,0.5 to 50.0 ng/mL for 2-Oxo-CLP,and 0.5 to 100 ng/mL for clopidogrel active metabolite derivative(CAMD).The retention time was 4.78 minutes,3.79 minutes,3.59 minutes,and 4.82 minutes for clopidogrel,2-Oxo-CLP,CAMD,and internal standard,respectively.Both the relative standard deviation and the relative error were within the requirement of operating criteria.No significant degradation of clopidogrel,2-Oxo-CLP,and CAMD occurred under different storage conditions.This method was successfully validated in 3 patients with coronary artery disease.The results showed that the current LC-MS/MS method was efficient for simultaneously detecting clopidogrel,2-Oxo-CLP,and CAM with fine linearity,accuracy,precision,and stability.
Lei XuRan LiJuan LiZhou DongJiaxin ZongChuchu TanZekang YeLu ShiXiaoxuan GongChunjian Li
