Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践与服务

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.

Literature Case Analysis of 44 Patients with Thrombocytopenia Induced by Clopidogrel / 医药导报

Objective To investigate the characteristics of clopidogrel-associated thrombocytopenia to provide references for clinically safe drug use.Methods The case reports of thrombocytopenia induced by clopidogrel published in PubMed,Embase,CNKI,Wanfang and VIP were searched from the establishment of each database to November 2022,and their occurrence was collated and analysed.Results A total of 44 cases from 43 articles were identified and included in the analysis.There were 30 males(68.2％)and 14 females(31.8％).Ages ranged from 37 to 88(65.0±11.4)years,of which 30(68.2％)were ≥60 years old.Thrombocytopenia was found from 8 h to 9 months after medication,of which 29 cases(65.9％)appeared within two weeks.There were 31 cases(70.5％)with severe thrombocytopenia and 38 cases(86.4％)with complications,of which 24 cases(63.2％)with bleeding and 19 cases(50.0％)with thrombotic thrombocytopenic purpura(TTP).The platelet countof41 cases(93.2％)returned to normal after drug withdrawal and symptomatic treatment,and 3 cases(6.8％)died finally.Conclusion Clopidogrel related thrombocytopenia is mainly severe thrombocytopenia,and often accompanied by bleeding or thrombotic thrombocytopenic purpura(TTP),but the overall outcome is good.Platelet count should be regularly monitored within the first two weeks after medication.Clopidogrel should be stopped and symptomatic treatment should be given in case of any abnormality.

Effect of Ticagrelor on Left Ventricular Function in Patients with Mildly Reduced Ejection Fraction after Acute Myocardial Infarction

Abstract Background There are limited data about the effect of new P2Y12 inhibitors on left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI). Objectives We aimed to investigate the effect of ticagrelor on left ventricular function, compared to clopidogrel in patients with heart failure with mildly reduced ejection fraction (HFmrEF) after AMI. Methods In this cross-sectional, single-center study, we included 251 patients with LVEF between 40% and 50% after AMI before discharge. The patients were divided into 2 groups according to the use of ticagrelor (166 patients) and clopidogrel (85 patients). At the end of the 12-month period, LVEF changes were assessed by echocardiography. P < 0.05 was considered statistically significant. Results The mean LVEF before discharge was 46.5% ± 3.6%, and no difference was observed between the ticagrelor and clopidogrel groups (p = 0.20). At the end of the first year, the mean LVEF of the patients increased to 49.8% ± 7.6% in both groups. The use of ticagrelor (β ± SE = 2.05 ± 0.93; p = 0.029), low creatinine level (β ± SE = −10.44 ± 2.35; p < 0.001), low troponin level (β ± SE = −0.38 ± 0.14; p = 0.006), and low heart rate (β ± SE = −0.98 ± 0.33; p = 0.003) were found to be independent predictors of the increase in LVEF (β ± SE 2.05 ± 0.93; 95% confidence interval: 0.21 to 3.90; p = 0.029). Conclusion In our study, ticagrelor improved left ventricular function in 12 months follow-up compared to clopidogrel in patients with HFmrEF after AMI.

Migraña poscierre percutáneo de defectos septales auriculares / Migraine after percutaneous closure of atrial septal defects / Enxaqueca após fechamento percutâneo de comunicação interatrial

La migraña es una enfermedad que se ha visto asociada a defectos septales auriculares y a su cierre percutáneo, estipulándose en la literatura que sería una rara complicación, pero la evidencia al respecto es escasa. Se realizó una revisión narrativa sobre definiciones, epidemiología, fisiopatología y tratamiento de la migraña y de la entidad migraña poscierre percutáneo de defectos del septum auricular, incluyendo trabajos observacionales (retrospectivos, prospectivos), estudios randomizados, reportes de casos, artículos de revisión y metaanálisis existentes en PubMed y Cochrane, para aportar al conocimiento de esta entidad.

Migraine is a disease that has been associated with atrial septal defects and its percutaneous closure, stipulating in the literature that it would be a rare complication, but evidence is scarce. A narrative review was conducted on definitions, epidemiology, pathophysiology and treatment of migraine and the migraine entity after percutaneous closure of atrial septum defects, including observational studies (retrospective, prospective), randomized studies, case reports, review articles and meta-analyses existing in PubMed and Cochrane, to contribute to the knowledge of this entity.

A enxaqueca é uma doença que tem sido associada a defeitos do septo atrial e seu fechamento percutâneo, estipulando na literatura que seria uma complicação rara, mas as evidências são escassas. Foi realizada uma revisão narrativa sobre definições, epidemiologia, fisiopatologia e tratamento da enxaqueca e da entidade migranosa após fechamento percutâneo de defeitos do septo atrial, incluindo estudos observacionais (retrospectivos, prospectivos), estudos randomizados, relatos de caso, artigos de revisão e metanálises existentes no PubMed e Cochrane, para contribuir com o conhecimento dessa entidade.

Dual antiplatelet therapy in patients with minor stroke or high-risk transient ischemic attack carrying CYP2C19 loss-of-function alleles / 国际脑血管病杂志

Dual antiplatelet therapy has been widely used for the secondary prevention in patients with minor stroke and high-risk transient ischemic attack (TIA). Currently, the commonly used antiplatelet drugs are aspirin and clopidogrel. The therapeutic effect of antiplatelet drugs varies among individuals, namely platelet resistance. Among them, aspirin resistance is often caused by poor drug compliance, while clopidogrel resistance is often associated with CYP2C19 allele mutations. Patients with minor stroke and high-risk TIA carrying CYP2C19 loss-of-function alleles have poor preventive effects when using clopidogrel. Early screening of the CYP2C19 loss-of-function alleles and targeted measures can benefit such patients. This article reviews the research progress on the selection of antiplatelet therapy for minor stroke or high-risk TIA patients carrying the CYP2C19 loss-of-function alleles.

High on-treatment platelet reactivity in patients with ischemic stroke or transient ischemic attack / 国际脑血管病杂志

Antiplatelet drugs are the cornerstone of long-term treatment and secondary prevention for ischemic stroke/transient ischemic attack (TIA) recommended by guidelines, aimed at reducing the risk of recurrent stroke and other cardiovascular events. However, some patients with ischemic stroke/TIA may still experience ischemic events during antiplatelet therapy, known as high on-treatment platelet reactivity (HTPR), which typically occurs in patients taking aspirin or clopidogrel. This article elaborates the incidence, risk factors, and commonly used evaluation methods of HTPR in patients with ischemic stroke/TIA, and elucidates the clinical significance of HTPR in patients with ischemic stroke/TIA, and investigates the antiplatelet treatment protocol of patients with HTPR.

Risk Factors of Clopidogrel Resistance in the Elderly Patients with Atherosclerotic Cardiovascular Disease / 中国医学科学院学报

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.

Efficacy and safety of extended dual antiplatelet therapy beyond 12 months after coronary artery bypass grafting / 中华胸心血管外科杂志

Objective:To investigate the efficacy and safety of prolonged dual antiplatelet therapy (DAPT) (aspirin + clopidogrel) after coronary artery bypass grafting (CABG) for more than 12 months.Methods:1 900 patients who received CABG treatment in Tianjin Chest Hospital from January 2019 to October 2020 were continuously included, and 1 528 patients were finally identified according to the inclusion and exclusion criteria. According to whether the patients continued to take DAPT treatment 12 months after discharge, they were divided into the extended DAPT group and the standard DAPT group. Cox multivariate regression and propensity score matching (PSM) analysis were performed on major cardiovascular and cerebrovascular adverse events (MACCE) and clinically related bleeding events in the two groups during 12-24 months after discharge to evaluate the efficacy and safety of extended DAPT treatment for more than 12 months. Results:Of the 1 528 patients, 624 (40.8%) continued to take DAPT 12 months after discharge. Compared with patients receiving standard DAPT, patients receiving extended DAPT had a lower incidence of MACCE within 12 to 24 months ( HR=0.597, 95% CI: 0.399-0.892, P=0.012); ( HR=0.519, 95% CI: 0.338-0.798, P=0.003), and there was no significant increase in clinically relevant bleeding risk ( HR=1.209, 95% CI: 0.522-2.798, P=0.658), ( HR=1.112, 95% CI: 0.452-2.737, P=0.817). At the same time, prolonged DAPT treatment also brought a good net benefit. Conclusion:Prolonged DAPT treatment after CABG for more than 12 months significantly reduced the risk of ischemia at 12-24 months after surgery, and did not significantly increase the risk of bleeding at 12-24 months after surgery. It may be beneficial for patients treated with CABG to continue DAPT (aspirin+ clopidogrel) on the basis of intensive DAPT therapy for 1 year.

Clinical effect of indobufen combined with clopidogrel on acute cerebral infarction / 中国现代医生

Objective To explore the clinical effect of indobufen combined with clopidogrel on acute cerebral infarction and analyze the drug safety.Methods Using a randomized and controlled clinical study method,72 patients with acute cerebral infarction selected in Wenzhou Central Hospital from June 2021 to December 2022 were included in the study.They were randomly divided into control group and experimental group.The experimental group was given indobufen tablets 200mg(twice daily),and clopidogrel 75mg every day.The control group was treated with clopidogr el 75mg every day.The two groups were treated with conventional internal medicine in the department of neurology.They were given Xingnaojing Injection 20mg every day,and Butylphthalide Injection 100ml(twice daily).And they were given symptomatic support treatment with drugs to improve cerebral circulation and drugs to reduce blood fat and stabilize plaque.In addition,we control patients'basic diseases such as hypertension and hyperglycemia.The indexes of cerebral infarction related scale were evaluated before treatment and after 3 weeks.Results After 3 weeks of treatment,the scores of stroke scale in the experimental group and the control group were lower than those before treatment.The total effective rate in the experimental group was higher than that in the control group,the difference was statistically significant(P<0.05).The score of Quality of Life in the experimental group was significantly higher than that before treatment(P<0.001).The score of Quality of Life in the control group was higher than that before treatment(P<0.05).Compared with the control group,the Quality of Life score of the experimental group was higher,with statistical significance(P<0.05).The incidence of stomachache and acid reflux in the two groups was low,and there was no statistically significant difference between the two groups(P>0.05).No gastrointestinal bleeding and intracranial hemorrhage occurred in the two groups.Conclusion Indobufen combined with clopidogrels can improve the treatment effect and Quality of Life score of patients with acute cerebral infarction,and is more obvious than clopidogrel alone.In addition,compared with clopidogrel monotherapy,indobufen combined with clopidogrel did not significantly increase the incidence of adverse reactions in patients.

A real-world study of effectiveness and safety of generic and original clopidogrel in the treatment of acute coronary syndrome / 中国药房

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.

Efficacy analysis of anti-platelet in the treatment of high-risk non-disabling ischemic cerebrovascular events guided by point-of-care testing of CYP2C19 gene / 中华神经科杂志

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

Pharmacoeconomic evaluation of clopidogrel versus aspirin for secondary prevention of ischemic stroke / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.

Dual antiplatelet therapy in stent-assisted coil embolization of unruptured intracranial aneurysms: a comparison of ticagrelor and clopidogrel / 国际脑血管病杂志

Objective:To compare the safety and efficacy of ticagrelor and clopidogrel in dual antiplatelet therapy for stent-assisted embolization of unruptured intracranial aneurysms.Methods:Patients with unruptured intracranial aneurysms received stent-assisted embolization in the Department of Neurosurgery, Linyi People's Hospital from January 2021 to June 2022 were retrospectively included. According to the preprocedural dual antiplatelet therapy scheme, they were divided into aspirin+clopidogrel group (clopidogrel group) and aspirin+ticagrelor group (ticagrelor group). The incidence of ischemic and bleeding events was compared between the clopidogrel group and the ticagrelor group at 3 months after procedure. Multivariate logistic regression model was used to analyze independent risk factors for postprocedural ischemic and bleeding events. Results:A total of 195 patients were included. Their age was 58.15±10.11 years and 75 were males (38.5%). There was no statistically significant difference in the incidence of bleeding events (12.8% vs. 5.9%) and ischemic events (14.9% vs. 18.8%) at 3 months after procedure between the ticagrelor group ( n=94) and the clopidogrel group ( n=101). Multivariate logistic regression analysis showed that smoking (odds ratio [ OR] 6.085; 95% confidence interval [ CI] 1.589-13.012; P=0.019], hypertension ( OR 4.547, 95% CI 1.589-13.012; P=0.005), aneurysm at the branch vessel ( OR 3.089, 95% CI 1.122-8.504; P=0.029), and the use of flow diverter ( OR 3.111, 95% CI 1.062-9.110; P=0.038) were the independent risk factors for postprocedural ischemic events. Triglycerides might be an independent risk factor for postprocedural bleeding events ( OR 1.435, 95% CI 0.989-2.082; P=0.057), but did not reach statistical significance. Conclusions:In dual antiplatelet therapy for stent-assisted embolization of unruptured intracranial aneurysms, ticagrelor and clopidogrel have the same safety and efficacy.

The evaluation value of cytochrome P450 2C19 *2 gene polymorphism, Helicobacter pylori infection for clopidogrel effect in patients with coronary heart disease / 中国医师进修杂志

Objective:To explore the evaluation of cytochrome P450 2C19 *2 (CYP2C19 *2) gene polymorphism and Helicobacter pylori (Hp) infection for clopidogrel efficacy in patients with coronary heart disease. Methods:The clinical data of 113 patients with coronary heart disease from February 2016 to March 2020 in Suzhou High-tech Zone People′s Hospital were retrospectively analyzed. The CYP2C19 *2 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the Hp infection was detected by 13C urea breath test. The patients were treated with clopidogrel, the effect after 4 weeks was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the CYP2C19 *2 gene polymorphism and Hp infection for evaluating clopidogrel effect in patients with coronary heart disease. Results:The CYP2C19 *2 genotype in patients with coronary heart disease conformed to Hardy-Weinberg balance ( χ2 = 0.33, P>0.05). Among 113 patients with coronary heart disease, Hp infection was in 27 cases, and Hp non-infection in 86 cases. Among Hp infection patients, CYP2C19 *2 gene GG was in 2 cases, GA in 6 cases, AA in 19 cases; among Hp non-infection patients, CYP2C19 *2 gene GG was in 23 cases, GA in 46 cases, AA in 17 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two ( χ2 = 24.35, P<0.01). After clopidogrel treatment, effectiveness was in 79 cases, inefficiency in 34 cases. Among effectiveness patients, YP2C19 *2 gene GG was in 20 cases, GA in 43 cases, AA in 16 cases; among inefficiency patients, CYP2C19 *2 gene GG was in 5 cases, GA in 9 cases, AA in 20 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two groups ( χ2 = 16.35, P<0.01). The rate of Hp infection in effectiveness patients was significantly lower than that in inefficiency patients: 12.66% (10/79) vs. 50.00% (17/34), and there was statistical difference ( χ2 = 18.23, P<0.05). ROC curve analysis result showed that the area under the curve of CYP2C19 *2 gene polymorphism combined with Hp infection for evaluating clopidogrel effect in patients with coronary heart disease was larger than CYP2C19 *2 gent GG, GA, AA and Hp infection alone evaluating (0.973 vs. 0.869, 0.679, 0.884 and 0.728) . Conclusions:The CYP2C19 *2 gene polymorphism is associated with Hp infection in patients with coronary heart disease, and the CYP2C19 *2 gene polymorphism combined with Hp infection has the evaluation value for the efficacy of clopidogrel.

Efficacy of Different Doses of Clopidogrel in Combination with Aspirin in Patients with HR-NICE by Point-of-care Testing of CYP2C19 Gene / 医学研究杂志

Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cy-tochrome P-450 2C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assess-ment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele car-riers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conven-tional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)inthein-tensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ2 = 16.827,P<0.001);0 case(0)in the intensive group and1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclu-sion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conven-tional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.

Correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis / 中国基层医药

Objective:To investigate the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Methods:A total of 148 patients with cerebrovascular stenosis who underwent neurovascular intervention at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to December 2020 were included in this study. The platelet function of patients before and 24 hours after antiplatelet drug treatment was recorded. Platelet drug resistance was analyzed. At 3, 6 months, and 1 year after neurovascular intervention, adverse events were recorded through follow-up. The patients were divided into the occurrence group and the non-occurrence group according to whether adverse events occurred or not using the case-control study method. The Spearman correlation coefficient was used to analyze the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Results:After 1 year of follow-up, among the 148 patients, 29 patients lost their follow-up, and 119 were included in the final analysis. Of the 119 patients, 41 patients had adverse events and 78 patients had no adverse events. In the occurrence group, the expression levels of platelet membrane glycoprotein P-selectin and platelet activating complex were (20.22 ± 6.33)% and (68.80 ± 11.52)%, respectively, before drug treatment, and they were (15.77 ± 4.12)% and (43.19 ± 5.90%)%, respectively, after drug treatment, all of which were significantly higher than those in the non-occurrence group [before drug treatment: (16.85 ± 3.24)%, (62.34 ± 10.77)%, after drug treatment: (8.31 ± 2.97)%, (35.85 ± 5.14)%] (before drug treatment: t = 3.20, 2.97, both P < 0.05; after drug treatment: t = 10.28, 6.74, both P < 0.05). The incidences of aspirin resistance and clopidogrel resistance in the occurrence group were 51.2% (21/41) and 43.9% (20/41), respectively, which were significantly higher than 26.9% (8/78) and 19.2% (9/78) in the non-occurrence group ( χ2 = 24.47, 20.23, both P < 0.001). Spearman correlation analysis showed that both aspirin resistance and clopidogrel resistance were moderately positively correlated with adverse events after neurovascular intervention ( r = 0.45, 0.41, both P < 0.05). Conclusion:Adverse events after neurovascular intervention are moderately positively correlated with resistance to the antiplatelet drugs aspirin and clopidogrel.

Ácido acetilsalicílico versus inibidores dos receptores P2Y12 para prevenção secundária em pacientes tratados por meio de intervenção coronária percutânea / Aspirin versus P2Y12 inhibitors for secondary prevention after percutaneous coronary intervention

Na atualidade, as intervenções coronárias percutâneas com implante de um stent farmacológico constituem o principal método de revascularização miocárdica em centros hospitalares terciários, independentemente da forma clínica de apresentação da doença arterial coronária. É de conhecimento geral que, para sua efetivação, há necessidade do uso de um esquema antiplaquetário duplo, constituído pela associação do ácido acetilsalicílico e um inibidor dos receptores plaquetários P2Y12, que é o cerne da prevenção das tromboses após implantes das endopróteses, sendo também indicado para prevenir a ocorrência de eventos aterotrombóticos na evolução clínica tardia, qualquer que seja o modelo de stent utilizado. Após período variável de tempo, independentemente de fatores como forma clínica de apresentação da coronariopatia e do tipo de stent implantado, esse esquema é interrompido, e, na atualidade, as principais diretrizes preconizam a suspensão do inibidor dos receptores P2Y12 e a manutenção do ácido acetilsalicílico em longo prazo como uma das principais medidas farmacológicas de prevenção secundária da aterosclerose. No entanto, recentemente, em razão de sua maior potência antiplaquetária e provável menor potencial de causar hemorragias significantes, em especial no tubo digestivo, os inibidores P2Y12 têm sido considerados alternativa válida e atraente como antiplaquetário de utilização em longo prazo, alternativa ainda não referendada pelas diretrizes. Esta revisão discute os pormenores relacionados a essa importante decisão que deve ser tomada pelo cardiologista no momento da interrupção dos diferentes esquemas antitrombóticos inicialmente utilizados após uma intervenção coronária percutânea. Em princípio, a escassez de estudos clínicos conclusivos e normativos, em especial na população tratada por meio de uma intervenção percutânea, faz com que o ácido acetilsalicílico ainda se mantenha como o único antiagregante plaquetário com indicação classe I com a finalidade de prevenção secundária da aterosclerose.

Currently, percutaneous coronary intervention with a drug-eluting stent implantation is the main method of myocardial revascularization in tertiary care hospitals, regardless of the clinical presentation of coronary artery disease. It is well known that to be effective, it requires the use of a dual antiplatelet therapy, which is a combination of acetylsalicylic acid and a P2Y12 platelet receptor inhibitor, which plays a key role in preventing thromboses after endoprosthesis implantation and is also indicated to prevent atherothrombotic events in the late clinical course, regardless of the stent model used. After a variable period of time, depending on some factors, such as the clinical presentation of coronary artery disease and the type of stent implanted, this therapy is discontinued, and the main current guidelines recommend interrupting the P2Y12 receptor inhibitor and maintaining acetylsalicylic acid in the long term, as one of the main pharmacological measures for secondary prevention of atherosclerosis. However, recently, due to their greater antiplatelet potency and probable lower potential for significant bleeding, especially in the digestive tract, P2Y12 inhibitors have been considered a valid and attractive option as an antiplatelet agent for long-term use; but this alternative has not been endorsed by guidelines yet. This review discusses the details related to this important decision that must be made by cardiologists when discontinuing the different antithrombotic therapies initially used after percutaneous coronary intervention. In principle, the scarcity of conclusive and normative clinical studies, especially in the population treated by percutaneous intervention, means that acetylsalicylic acid is the only antiplatelet agent with class I indication for secondary prevention of atherosclerosis.

Sangramiento posextracción dentaria y medidas para su control en pacientes tratados con antiagregantes plaquetarios / Bleeding after tooth extraction and measures for its control in patients treated with antiplatelet agents

Introducción: El desarrollo de las ciencias médicas trae consigo un incremento en la expectativa de vida, junto a la detección temprana de un gran número de enfermedades crónicas como las cerebrovasculares y cardiovasculares, que son tratadas rutinariamente con medicamentos antiagregantes plaquetarios. El conocimiento del manejo de estos pacientes ante los procedimientos quirúrgicos estomatológicos constituye un reto en la práctica diaria profesional. Objetivo: Determinar el nivel de sangramiento posextracción dentaria en pacientes con enfermedad cardiovascular y cerebrovascular, según el tipo de antiagregantes plaquetarios y grupo dentario, así como la frecuencia de utilización de las medidas para su control. Métodos: Se efectuó un estudio observacional, descriptivo, longitudinal y prospectivo con un universo de 136 pacientes de más de 20 años, remitidos por su cardiólogo y que necesitaban realizarse extracciones dentarias sin modificar su tratamiento con antiagregantes plaquetarios. Las variables estudiadas fueron la enfermedad sistémica, el tipo de antiagregante plaquetario, el nivel de sangramiento, grupo dentario intervenido y método hemostático utilizado. Resultados: La mitad de los pacientes estudiados no presentó sangramiento posextracción dentaria. En los pacientes tratados con aspirina o clopidogrel predominaron los sujetos sin sangramiento para un 84,3 por ciento y 62,5 por ciento, respectivamente. En los de doble antiagregación prevaleció el sangramiento moderado con un 46,3 por ciento. Los grupos dentarios incisivo, canino y premolar no presentaron episodios de sangramiento para un 64,1 por ciento, 51,6 por ciento y 53,3por ciento, respectivamente. El método hemostático más utilizado fue la compresión de las corticales y termoterapia fría (47,8 por ciento). Conclusiones: La mitad de los pacientes con enfermedades cardiovasculares y cerebrovasculares no presentaron sangramiento posextracción dentaria(AU)

Introduction: The development of medical sciences brings with it an increase in life expectancy, together with the early detection of a large number of chronic diseases such as cerebrovascular and cardiovascular diseases, which are routinely treated with antiplatelet aggregation drugs. Knowledge on the treatment of these patients before stomatological surgical procedures constitutes a challenge in daily professional practice. Objective: To determine the level of bleeding after tooth extraction in patients with cardiovascular and cerebrovascular disease, according to the type of antiplatelet agents and dental group, as well as the frequency of use of measures for their control. Methods: An observational, descriptive, longitudinal and prospective study was carried out with a universe of 136 patients over 20 years of age, referred by their cardiologist, who needed dental extractions without modifying their treatment with antiplatelet agents. The variables studied were systemic disease, type of antiplatelet agent, level of bleeding, dental group treated and hemostatic method used. Results: Half of the patients studied did not present bleeding after tooth extraction. In patients treated with aspirin or clopidogrel, 84.3 percent and 62.5por ciento, respectively, had no bleeding. In those with double antiplatelet therapy, modera te bleeding prevailed with 46.3 The incisor, canine and premolar tooth groups did not present bleeding episodes (64.1 percent, 51.6and 53.3 percent respectively). The most commonly used hemostatic method was cortical compression and cold thermotherapy (47.8%). Conclusions: Half of the patients with cardiovascular and cerebrovascular diseases did not present bleeding after tooth extraction(AU)

Effect of Anti?Platelet Therapy on Peri?Operative Blood Loss in Patients Undergoing Off?Pump Coronary Artery Bypass Grafting

Purpose:The purpose of this study was to review the effect of the pre?operative use of clopidogrel and aspirin on peri?operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG). Materials and Methods: A total of 1200 patients who underwent off?pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on?pump CABG, and the combined procedure were excluded from the study. Results: Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post?operatively, this was statistically significant. Re?exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients. Conclusion: The pre?operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.