Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Pat...Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function （LOF） and gain of function （GOF） genotype,adenosine 5＇-diphosphate （ADP）-channel platelet inhibition rate （PIR） tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results：High on-treatment platelet reactivity （HTPR） prevalence defined by PIR 〈30% by TEG in ADP-channel was 32.76% （38/116）.With respect to the normal wild type,CYP2C 19＊2,and ＊3 LOF alleles,and ＊ 17 GOF alleles,patients were classified into three metabolism phenotypes：41.38% were extensive metabolizers （EMs）,56.90% were intermediate metabolizers （IMs）,and 1.72% were poor metabolizers （PMs）.Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of ＊2,＊3,and ＊ 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen （17.24%） ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions：Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.展开更多
Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population...Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.展开更多
目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳...目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳入标准的临床研究进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价,再采用Rev man 5.1统计软件进行Meta分析。结果:共纳入17项RCT,合计2 757例患者。Meta分析结果显示,负荷剂量下,无论采用Verify Now P2Y12(VN)检测法[MD=15.43,95%CI(-0.39,31.25),P=0.06]或血管扩张刺激磷酸蛋白(VASP)检测法[MD=-3.04,95%CI(-8.98,2.90),P=0.32],替格瑞洛与普拉格雷对血小板反应性的效果相当,两组比较差异均无统计学意义;维持剂量下,无论采用VN检测法[MD=-48.94,95%CI(-58.04,-39.84),P<0.001]或VASP检测法[MD=-14.32,95%CI(-20.45,-8.20),P<0.001],替格瑞洛对血小板反应性的效果均优于普拉格雷,两组比较差异均有统计学意义。结论:在初期负荷剂量使用抗血小板药物时,选用替格瑞洛或普拉格雷对血小板反应性的影响没有显著差异,而后期维持剂量使用抗血小板药物时,替格瑞洛对血小板反应性的效果优于普拉格雷。展开更多
Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center...Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.展开更多
文摘Background：To investigate the contributions ofCYP2C 19 polymorphisms to the various clopidogrel responses tested by thrombelastography （TEG） in Chinese patients with the acute coronary syndrome （ACS）.Methods：Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy.CYP2C 19 loss of function （LOF） and gain of function （GOF） genotype,adenosine 5＇-diphosphate （ADP）-channel platelet inhibition rate （PIR） tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients.Results：High on-treatment platelet reactivity （HTPR） prevalence defined by PIR 〈30% by TEG in ADP-channel was 32.76% （38/116）.With respect to the normal wild type,CYP2C 19＊2,and ＊3 LOF alleles,and ＊ 17 GOF alleles,patients were classified into three metabolism phenotypes：41.38% were extensive metabolizers （EMs）,56.90% were intermediate metabolizers （IMs）,and 1.72% were poor metabolizers （PMs）.Of the enrolled patients,31.47%,5.17%,and 0.43%,respectively,were carriers of ＊2,＊3,and ＊ 17 alleles.The HTPR incidence differed significantly according to CYP2C 19 genotypes,accounting for 18.75%,41.54%,and 100.00% in EMs,IMs,and PMs,respectively.Eighteen （17.24%） ischemic events occurred during the 3-month follow-up,and there was a significant difference in ischemic events between HTPR group and nonhigh on-treatment platelet reactivity group.Conclusions：Genetic CYP2C 19 polymorphisms are relative to the inferior,the antiplatelet activity after clopidogrel admission and may increase the incidence of ischemic events in patients with ACS.
文摘Background The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. However, the effect of coexisting polymorphisms of other genes has not yet been reported in the Chinese population. This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patients. Methods In 577 Han Chinese patients undergoing stent placement because of acute coronary syndrome had platelet reactivity assessed by thromboelastography, and the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase detection reaction. Primary clinical endpoints included cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, and stent thrombosis. The secondary clinical endpoints were thrombolysis in myocardial infarction bleeding. The follow-up period was 12 months. Results Genotyping revealed 194 carriers of the wild type GG genotype of CYP2C19 and the wild type CC genotype of P2Y12 （group 1）, 102 carriers of the wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 （group 2）, 163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype of P2Y12 （group 3）, and 118 carriers of the mutational A allele of CYP2C19 and the mutational T allele of P2Y12 （group 4）. Group 4 had the lowest ADP-inhibition （49.74＋32.61） and the highest prevalence of clopidogrel low response （29.7%） of the four groups. The rate of the composite of primary clinical endpoints increased more in group 4 （8.5%） than in the other three groups; the rate of composite primary endpoints in group 2 （2.9%） and group 3 （3.7%） were not significantly different than that of group 1 （1.5%）. Conclusion Coexisting polymorphisms of different genes affected clopidogrel responsiveness and clinical outcome more than single polymorphism in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention.
文摘目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳入标准的临床研究进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价,再采用Rev man 5.1统计软件进行Meta分析。结果:共纳入17项RCT,合计2 757例患者。Meta分析结果显示,负荷剂量下,无论采用Verify Now P2Y12(VN)检测法[MD=15.43,95%CI(-0.39,31.25),P=0.06]或血管扩张刺激磷酸蛋白(VASP)检测法[MD=-3.04,95%CI(-8.98,2.90),P=0.32],替格瑞洛与普拉格雷对血小板反应性的效果相当,两组比较差异均无统计学意义;维持剂量下,无论采用VN检测法[MD=-48.94,95%CI(-58.04,-39.84),P<0.001]或VASP检测法[MD=-14.32,95%CI(-20.45,-8.20),P<0.001],替格瑞洛对血小板反应性的效果均优于普拉格雷,两组比较差异均有统计学意义。结论:在初期负荷剂量使用抗血小板药物时,选用替格瑞洛或普拉格雷对血小板反应性的影响没有显著差异,而后期维持剂量使用抗血小板药物时,替格瑞洛对血小板反应性的效果优于普拉格雷。
基金The present trial was supported by grants from the National Science Foundation of China （No. NSFC 81770342）, Nanjing Health and Family Planning Commission （No. YKK16124）, and Nanjing Municipal Commission of Science and Technology （No. 201715026）.
文摘Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.
