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Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.
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Objective To explore the risk factors of clopidogrel resistance (CR) in the elderly patients with atherosclerotic cardiovascular disease and to provide evidence for the antiplatelet therapy. Methods A total of 223 elderly patients (≥80 years old) with atherosclerotic cardiovascular disease treated in the Department of Geriatrics in the Peking University People's Hospital from January 18,2013 to November 30,2019 and meeting the inclusion criteria were enrolled in this study.The clinical data and laboratory test results were collected,including clinical disease,drug use,physical examination,complete blood cell analysis,biochemical indicators,and thromboelastogram (TEG).The rate of platelet inhibition induced by adenosine diphosphate was calculated according to the TEG.We assigned the patients into a CR group (n=84) and a control group (n=139) to analyze the incidence and influence factors of CR in the elderly patients with atherosclerotic cardiovascular disease. Results The incidence of CR was 37.7% in the elderly patients with atherosclerotic cardiovascular disease.The CR group had lower hemoglobin (t=3.533,P=0.001) and higher hypertension prevalence rate (χ2=6.581,P=0.006),proportion of multiple drugs (χ2=3.332,P=0.048),body mass index (BMI) (t=-2.181,P=0.030),total cholesterol (t=-2.264,P=0.025),triglycerides (Z=-2.937,P=0.003),low-density lipoprotein cholesterol (LDL-C) (t=-2.347,P=0.020),and proportion of women (χ2=5.562,P=0.014) than the control group.The results of multivariate Logistic regression showed that hemoglobin (OR=0.962,P<0.001),BMI (OR=1.154,P=0.003),and LDL-C (OR=1.688,P=0.018) were the factors influencing CR in the elderly patients with atherosclerotic cardiovascular disease. Conclusion Hemoglobin,BMI,and LDL-C may be independent factors associated with the occurrence of CR in the elderly patients with atherosclerotic cardiovascular disease.
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Aged , Aged, 80 and over , Female , Humans , Atherosclerosis , Cardiovascular Diseases , Cholesterol, LDL , Clopidogrel/therapeutic use , Risk FactorsABSTRACT
Objective:To analyze the relationship between CYP2C19 polymorphism and clopidogrel resistance (CR) in patients with acute coronary syndrome (ACS).Methods:One hundred and twenty-seven ACS patients treated with percutaneous coronary intervention (PCI) from June 2019 to June 2020 were enrolled, including 29 patients with CR(CR group) and 98 patients with none clopidogrel resistance (NCR, NCR group). The clinical data, coronary angiography results were compared between the two groups, the relationship of CYP2C19*2 and CYP2C19*3 polymorphisms and CR were analyzed.Results:The general data and coronary angiography between two groups had no significant differences ( P>0.05). There were differences in the distribution of isogenic genes and genotypes of CYP2C19 (rs4244285) and CYP2C19 (rs4986893) between the two groups ( P<0.05). Polymorphism of CYP2C19*2 and CYP2C19*3 was an important risk factor for CR ( OR = 14.688, 95% CI 3.652-59.063, P<0.01; OR = 7.228, 95% CI 2.412-21.663, P<0.01). Conclusions:CR is closely associated with CYP2C19*2 and CYP2C19*3 in ACS patients.
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Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.
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AIM: To investigate the effect of the polymorphism and metabolic type of cytochrome P450 (CYP) 2C19 gene on the inhibitory rate of platelet aggregation induced by ADP and relationship with resistance of clopidogrel. METHODS: A total of 163 patients that are administrated with aspirin and clopidogrel were collected from the Yijishan Hospital of Wannan Medical College from June 2016 to July 2017. The CYP2C19*2, *3 and *17 genotypes of patients were detected with fluorescence staining in situ hybridization, according to the genotype, CYP2C19 enzyme activity was divided into fast metabolic (RM), intermediate metabolic (IM), slow metabolic (PM) and ultrafast metabolic type (UM). After 5 days of drug delivery, the platelet aggregation inhibition rate (IPAADP) induced by ADP was detected by thrombus elasto graph. IPAADP differences between CYP2C19*2, *3 and *17 genotype and CYP2C19 enzyme metabolic type were evaluated. CYP2C19 genotype and metabolic type as well as their distribution in clopidogrel resistance group (CR) and non clopidogrel resistance group (NCR) were observed. RESULTS: The mutation rates of CYP2C19*2, *3 and *17 were 30.98%, 6.75% and 1.23%, respectively. The average IPAADP was (67.03±26.79)% and the incidence of CR was 26.99%, and the IPAADP was (31.29±12.60)%. The IPAADP of CYP2C19*2 and *3 gene carriers were decreased significantly (P0.05). There was no statistical difference in the distribution of CYP2C19 genotypes and metabolic types in NCR and CR (P>0.05). CONCLUSION: CYP2C19 genotypes have significant effect on IPAADP, but there is no association with the occurrence of CR, and the related study needs to be further verified.
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Clopidogrel plays an important role in anti-platelet aggregation, especially in acute coronary syndrome and percutaneous coronary intervention. However, clopidogrel resistance is common in clinical treatment. There are many factors response to clopidogrel resistance.Current researches concentrated in CYP450 enzyme gene polymorphism with clopidogrel resistance. There are few reviews on genetic polymorphisms of transporter and receptor binding sites, furthermore, the gene polymorphisms among different ethnic groups in plateau populations are very rare. In this paper, we mainly reviewed the relationship between gene polymorphism of drug-transporter and bioavailability of clopidogrel, the whole process of drug-metabolizing enzyme′s bioconversion of clopidogrel and the active metabolite of clopidogrel combine with the receptors.A mutation in the ABCB1 gene of the transporter was found to affect the bioavailability of clopidogrel. The key role of polymorphisms in the metabolic enzyme gene is CYP2C19 and CES1. The dose should be adjusted according to genotyping. The biologically active gene P2Y12 polymorphism affects the efficacy of clopidogrel. Therefore, understanding the clopidogrel gene polymorphism influencing factors can help individualized administration of clopidogrel to minimize thrombotic events caused by insufficient antiplatelet effect or hemorrhagic events caused by excessive anti-platelet effect.
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Objective To investigate the correlation between Paraoxonase-1 (PON-1) gene Q192R polymorphism and clopidogrel resistance (CR). Methods A total of 118 patients with coronary artery disease diagnosed by coronary angiography or coronary artery CT angiography were enrolled. Platelet aggregation rate was assessed by ADP-induced light-transmittance aggregometry after the patients received adequate clopidogrel pretreatment.The patients were divided into (clopidogrel resistance group (CR group) and non-clopidogrel resistance group (NCR group) according to the ADP-induced platelet aggregation rate. The gene of Q192R was detected by MassARRAY Time of Flight Mass Spectrometry.The genotypes and allele frequencies between the two groups were compared. Results According to the ADP-induced platelet aggregation rate,25 patients were defined as clopidogrel resistant and 93 as non-clopidogrel resistant.The incidence of clopidogrel resistance was 21.2％.Three frequencies of genotype RR,QR and QQ were 36. 0％,52. 0％ and 12. 0％ in CR group, and 32. 2％,57. 0％ and 10. 8％ in NCR group, respectively.The frequencies of Q and R allele in CR group were 62.0％ and 38.0％,and those in NCR group were 60.8％ and 39.2％.No significant differences in genotype and allele frequency were found between CR group and NCR group (P>0.05). Conclusion The PON-1 gene Q192R polymorphism is not associated with clopidogrel resistance in patients with CHD.
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Clopidogrel is one of the anti-platelet drugs, which is widely used in the world.It plays an important role in the treatment of patients with acute coronary syndrome and those undergoing percutaneous coronary intervention.Clopidogrel is effective in inhibiting the activity of platelets, decreasing the incidence of thrombosis in the stent, and then reducing the risk of adverse cardiovascular events in affected individuals. However, some patients still have coronary thrombosis after taking clopidogrel.This phenomenon is known as clopidogrel resistance or clopidogrel non-response or low response. Identification of clopidogrel resistance is of great significance in preventing the occurrence of adverse cardiovascular events.This paper provides guidance for the clinical treatment of clopidogrel resistance by discussing the definition, mechanisms and laboratory evaluation of clopidogrel resistance.
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Objective To explore the influence of smoking on clopidogrel resistance in patients with coro-nary artery disease. Methods A total of 216 patients with coronary artery disease who accept selective percutane-ous coronary intervention in our hospital from May 2015 to December 2015 were selected as study subjects;their average age was 63 years old ,146 were male and 70 were female. All the patients were divided into clopidogrel resistance group (CR group) and normal clopidogrel response group (NCR group) according to the results of platelet aggregation test. History of smoking ,alcohol drinking and diabetes mellitus ,baseline medication uses , level of platelet counts,platelet distribution width,mean platelet volume,HbA1c,and results of echocardiogram and coronary angiography were compared between the two groups. Results The rate of smoking was significantly higher in CR group than in NCR group (P < 0.05). The changed value of PDW before and after treatment with clopidogrel was smaller in CR group than in NCR group ,the difference was statistically significant (P < 0.05). Conclusions Smoking may be a protective factor for clopidogrel resistance. The changed value of PDW before and after treatment with clopidogrel can reflect the level of clopidogrel resistance.
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Objective To study the effect of clopidogrel on different CYP2C19 genotypes and platelet reactivity in acute cerebral infarction patients with antiplatelet aggregation.Methods Four hundred and seventy-four cases of cerebral infarction patients in Beijing Tiantan Hospital Affiliated to Capital Medical University from April 2015 to April 2016 were collected.CYP2C19 genotype was determined,and the genotype was divided into the wild type group,the heterozygous type group and the mutant homozygous group.Platelet aggregation inhibition rate(ADP%) and platelet reactivity index induced by ADP were detected.Patients were divided into clopidogrel resistance group(group CR) and non resistant group according to whether ADP% was less than 30.SPSS 16.0 statistical software was used for statistical analysis,the comparison between groups using independent samples t test,chi square test and multivariate analysis using Logistic regression analysis,when P<0.05 difference was statistically significant.Results Among the 474 patients,204 cases(43.04%) were divided into wild-type group,and 204(43.04%) and 66(13.92%) were divided into the mutant heterozygous group and mutant homozygous group.In Chi square test analysis,clopidogrel resistance group and non resistance group CYP2C19 genotype distribution was significantly different(χ2=6.658,P=0.036).CR group angle(α) values((68.87±5.47)°) and MA((66.77±6.25) mm) were higher than that of CS group ((66.55±6.05)° and (63.30±5.66) mm,t=2.199,3.387,P=0.029,0.001).The multivariate logistic regression analysis showed that OR of angle level was 1.028,95%CI was 0.929-1.137 (P=0.595);OR of Ma level was 1.561,95%CI was 0.785-0.970 (P=0.012).Conclusion The effect of clopidogrel on platelet aggregation in patients with acute cerebral infarction is decreased by CYP2C19 gene mutation.CYP2C19 mutant allele is a risk factor for clopidogrel resistance.Angle (α) value and MA value are the risk factors for the diagnosis of CR in the patients with acute cerebral infarction,and the risk of clopidogrel resistance increased when the patients′ Angle (α) value and the value of MA increased.MA value as a predictor of CR and the screening tool has a certain value.
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Objective To provide reference for clinical pharmacist participating in the therapy for acute coronary syndrome. Methods Clinical pharmacist participated in the therapy for a case of acute coronary syndrome,helped physicians analyzing the possible reasons of anti-platelet drugs resistance, chose proper anti-platelet drug based on genetic testing, and adjusted the administration of statins. Results The platelet aggregation rate was reduced from 70.5% to 20.0%,and the liver injury was controlled after individualized medication. Conclusion The safety and efficacy of patients were improved through clinical pharmacist's actively participating in clinical practice .
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Objective To provide reference for clinical pharmacist participating in the therapy for acute coronary syndrome. Methods Clinical pharmacist participated in the therapy for a case of acute coronary syndrome,helped physicians analyzing the possible reasons of anti-platelet drugs resistance, chose proper anti-platelet drug based on genetic testing, and adjusted the administration of statins. Results The platelet aggregation rate was reduced from 70.5% to 20.0%,and the liver injury was controlled after individualized medication. Conclusion The safety and efficacy of patients were improved through clinical pharmacist's actively participating in clinical practice .
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Objective To analyze Clopidogrel Resistance (CR) and influencing factors of coronary heart disease (CHD) with diabetes (DM) patients and evaluatc the relationship of CR and major adverse cardiovascular events (MACE) and readmission of CHD with DM patients.Methods 270 CHD patients were enrolled.Clinical conditions of CR were measured by adenosine diphosphate (ADP) induced maximum platelet aggregation rate (MPAR).After 1-year follow-up,MACE events and rehospitalization were recorded.Results CR of NDM and DM patients were 45 (33.1％) and 78 cases (58.2％) respectively,and the difference was significant (P ＜ 0.001).Factors of CR of CHD DM patients included heart rate,TG level,the number of severe coronary artery disease.MACE events of CS and CR patients were 35 (23.8％) and 47 patients (38.2％) respectively,and the difference was significant (P =0.010).The readmitted patients of CS and CR groups were 15 cases (10.2％) and 27 patients (22.0％) respectively,and the differcnce was significant (P =0.008).The MACE of CR and CS patients in DM group were 32 (41.0％) and 12 cases (21.4％) respectively,and thc difference was significant (P ＜ 0.05).The Readmitted cases of CR and CS patients in DM group were 19 (24.4％) and 5 (8.9％) respectively,and the diffcrcnce was significant (P ＜ 0.05).Conclusions CR of CHD DM patients increased significantly.The influencing factors of CR of CHDDM are including heart rate,TG level,the number of severe coronary artery disease.MACE events and rehospitalization rate were significantly increased in CHD patients with DM AR.Therefore,it should be further strengthened the anti-platelet therapy for CHD patients with DM.
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Objective To screen patients with clopidogrel resistance and develop accurate anti-platelet therapy strategies based on CYP2C19 gene polymorphism.Methods A total of 200 patients with acute coronary syndrome/percutaneous coronary angioplasty were selected.The pyrophosphate sequencing technology was using to detect CYP2C19 gene polymorphism for identifying clopidogrel poor metabolizers and guide antiplatelet therapy according to the development of clopidogrel resistance strategies.Results The proportion of patients with clopidogrel resistance (including intermediate metabolizers and slow metabolizers) was about 63.5%.In clopidogrel intermediate metabolizers, 41.4% cases were applied double dosages of clopidogrel and about 20.2% patients were given ticagrelor instead of clopidogrel.For clopidogrel slow metabolizers, approximately 39.3% cases were given doubled dosage of clopidogrel and 46.4% cases were given ticagrelor.Compared with previous data, the proportion of individual treatment of clopidogrel resistance was significantly increased in this study.Conclusion The strategies for the treatment of clopidogrel resistance, which based on the polymorphism of CYP2C19 gene, have been achieved initial success.
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Objective:To systematically review the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel in the patients with cardiovascular and cerebrovascular diseases. Methods:Retrieved from MEDLINE,Embase,CNKI,Si-noMed and Wanfang Database (from January 1995 to December 2016),array researches about the association between P2Y12 genetic polymorphisms and the clinical safety of clopidogrel were collected including the studies of patients taking clopidogrel with cardiovascu-lar and cerebrovascular diseases and excluding animal experimental studies. The bias of recruited studies was assessed and meta-analy-sis was performed by RevMan 5.1 software. Results:Totally 10 array researches(3 in English and 7 in Chinese) were enrolled invol-ving 5 223 patients. There were no statistical differences between T allele gene carriers and CC genetype patients of C34T in the inci-dence of adverse cardiovascular events (RR=0.95,95% CI:0.82-1.09,P=0.46). The incidence of adverse cardiovascular events in T allele gene carriers of G52T was higher than that in GG genetype patients(RR=1.99,95% CI:1.63-2.44,P<0.000 01). The incidence of clopidogrel resistance in T allele gene carriers of C34T was higher than that in CC genetype patients(RR=2.02,95% CI:1.37-2.96,P=0.000 4). The incidence of clopidogrel resistance in T allele gene carriers of G52T was higher than that in GG gene-type patients (RR=1.56,95% CI:1.04-2.34,P=0.03). There was no statistical difference in the risk of clopidogrel resistance be-tween C allele gene carriers of i-T744c and T allele gene no-carriers(RR=0.99,95% CI:0.78-1.25,P=0.92). Conclusion:T al-lele gene carriers of C34T might be a risk factor of the occurrence of clopidogrel resistance,T allele gene carriers of G52T might be a risk factor of the occurrence of cardiovascular events and clopidogrel resistance,and C allele gene carriers of i-T744c might not increase the danger of the occurrence of clopidogrel resistance.
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Objective To investigate the relationship between the ABCB1 rs1045642 polymorphism and clopidogrel resistance (CR) among Chinese Han patients with ischemic stroke.Methods In total,110 patients with acute ischemic stroke were included in the study.Venous blood samples (2 mL) were collected after oral administration of 75 mg/d clopidogrel;the platelet aggregation rate was measured before clopidogrel administration and after 7 days of clopidogrel administration.CR is defined as no more than 10％ change in the platelet aggregation rate over two times.Based on the results,patients were divided into the CR group and non-CR (NCR) group.Genomic DNA was extracted,the target gene was amplified by PCR,and the SNP was determined by RFLP.Results The TT genotype frequency of ABCB1 rs1045642 was significantly higher in the CR group than in the NCR group (P =0.003).T allele carriers in CR group show much more (57.1％ vs 34％,P =0.001) compared with those in the NCR group.Conclusion The ABCB1 rs1045642 polymorphism may be an independent risk factor and the T allele may be a gene indicating risk for CR among Chinese Han patients with ischemic stroke.
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Abstract Objective Drug inhibition of platelet P2Y12 adenosine diphosphate receptor has reduced the incidence of adverse cardiovascular events after percutaneous coronary interventions. The analysis of the phosphorylation status of vasodilator-stimulated phosphoprotein by flow cytometry has shown a predictive value for adverse events and stent thrombosis. Polymorphisms of CYP2C19 in high risk patients may also relate to adverse cardiovascular events. Methods Ninety patients were enrolled. Patients received a 600 mg clopidogrel loading dose. Blood samples were obtained at the time of the procedure and 24 h later, platelet reactivity was assessed by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Low response to clopidogrel was defined as a platelet reactivity index ≥ 50%. The presence of CYP2C19*2 was identified with the restriction enzyme Smal. Results Mean platelet reactivity index: 53.45 ± 22.48% in the baseline sample and 57.14 ± 23.08% at 24 h (p = 0.183); 40% of patients behaved as good responders, the rest behaved as non-responders with 38% of patients showing platelet reactivity indexes between 50-70% and 22% showing indexes above 70%. The CYP2C19*2 polymorphism was found in 17% of patients, with a 3.9% AA homozygous genotype carriers. Conclusion Response to the clopidogrel loading dose showed a wide variability among patients with 40% responding to the drug according to previously established cut-off values. Our results showed that 3.9% of patients show the AA genotype. To our knowledge, this is the first study involving clopidogrel response by flow citometry and genotype typification in Mexican Mestizo population.
Resumen Objetivo La inhibición del receptor plaquetario P2Y12 se ha asociado con reducción en incidencia de eventos cardiovasculares mayores en pacientes sometidos a intervenciones coronarias percutáneas. El estudio de la fosfoproteína estimulada por vasodilatadores mediante citometría de flujo tiene valor predictivo para desarrollo de eventos adversos y trombosis del stent. Los polimorfismos del CYP2C19 en pacientes de alto riesgo pueden también asociarse con eventos adversos. Método 90 pacientes, dosis de carga de clopidogrel: 600 mg. Se obtuvieron muestras de sangre basales y post-24 horas. La reactividad plaquetaria se estudió mediante medición de fosfoproteína estimulada por vasodiatadores por citometría de flujo. Se consideró baja respuesta al clopidogrel un índice de reactividad plaquetaria ≥50%. La presencia del CYP2C19*2 se identificó con enzima de restricción Smal. Resultados La media del índice de reactividad plaquetaria fue: 53.45 ± 22.48% en muestras basales y 57.14 ± 23.08% a 24 h (p = 0.183); 40% de los pacientes repondieron a clopidogrel, el resto de comportó como no-respondedores, un 38%, mostró índices de reactividad plaquetaria entre 50 -70% y 22%, índices > 70%. El polimorfismo CYP2C19*2 se encontró en 17% pacientes, con un 3.9% portadores de genotipo homozigótico AA. Conclusiones La respuesta a clopidogrel mostró amplia variabilidad entre pacientes, el 40% presentó respuesta de acuerdo con puntos de corte pre establecidos. Un 3.9% de los pacientes presentó genotipo AA. Consideramos que este es el primer estudio realizado en población mestizo-mexicana utilizado citometría de flujo para evaluar la respuesta a clopidogrel así como la tipificación genética de los pacientes.
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Humans , Male , Female , Middle Aged , Polymorphism, Genetic , Ticlopidine/analogs & derivatives , Platelet Aggregation Inhibitors/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Ticlopidine/therapeutic use , Cross-Sectional Studies , Clopidogrel , MexicoABSTRACT
OBJECTIVE: To investigate the association between clopidogrel resistance (CR) with 3435C >T site polymorphism of ABCB1 gene. METHODS: The published articles were searched in the Pubmed, Science direct, Wiley online library, Web of Science, CNKI, CDDB database, and VIP. Search and sort out the article which is clopidogrel-resistance/clopidogrel-efficacy(CE) study about the relationship between CR and 3435C > T site polymorphism of ABCB1 gene, also combined with manually retrieving the references and similar results in the attached documents. The range of searching time was all from inception to June 25, 2014. RevMan5.0 software was used to conduct the Meta-analysis and other statistic analysis. RESULTS Six articles were included in our research. It showed that the total number of CR is 2 619, and the total number of CE is 2 799. While the result showed that there exist significant correlations between ABCB1 3435C >T loci polymorphism and CR in the allele gene model, dominant gene model, co-dominant gene model (CC/CT) and super-dominant gene model; the allele gene model, OR = 1.27, 95% CI (1.13, 1.42); dominant gene model, OR = 1.42, 95% CI (1.22, 1.65); co-dominant gene model (CC/CT), OR = 1.43, 95% CI (1.20, 1.69); super-dominant gene model, OR = 1.30, 95% CI(1.11, 1.52). The further race subgroup analysis showed that there possess significant relevance between ABCB1 3435C >T loci polymorphism and CR in Asia (P T loci polymorphism among European; but CR relates to the ABCB1 3435C > T loci polymorphism among Asian.
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OBJECTIVE: To evaluate the role of clinical pharmacist in individualized antiplatelet therapy in patients with percutaneous coronary intervention (PCI). METHODS: To review clinical pharmacist participating antiplatelet therapy based on genotype detection for one patient with stent thrombosis after PCI. RESULTS: Clinical pharmacist analyzed the causes of stent thrombosis after PCI by genotype detection, participated the adjustment of antiplatelet therapy and implemented pharmaceutical care and pharmaceutical education for the patient in order to ensure the safety and effectiveness of drug use. CONCLUSION: Clinical pharmacist participates making and regulating the therapeutic regimen to provide some evidences for individualized medication, which could be the entry points to pharmaceutical care.
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Objective: To observe the effect of Xueshuantong Injection on platelet aggregation in acute cerebral infarction patients with Clopidogrel resistance (CR). Methods: This study selected acute cerebral infarction patients with CR from March 2012 to August 2014 in Tianjin Hospital. Patients (104 cases) were randomly divided into two groups (n = 52). The patients in the control group were treated with Western Medicine and Clopidogrel 75 mg/d, and the patients in treatment group were treated with Western Medicine and Clopidogrel 75 mg/d and given Xueshuantong Injection (5 mL dissolved in 0.9% saline 250 mL, iv drip). The two groups were treated for 14 d. Results: The platelet aggregation in the two groups was reduced significantly after treatment (P < 0.05), and after treatment the platelet aggregation in the treatment group was lower than that in the control group (P < 0.05). Conclusion: Xueshuantong Injection can reduce platelet aggregation in acute cerebral infarction patients with CR, and is a beneficial supplement therapy for CR.