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.

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践杂志

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cuidados que o cirurgião-dentista deve tomar no momento de tratar cirurgicamente um paciente em uso de anticoagulantes ou antiagregantes plaquetários / Care that the dental surgeon must take when treating surgically a patient using anticoagulants or antiplatelet agents

Os anticoagulantes e antiagregantes plaquetários são medicamentos utilizados por uma grande parcela da população mundial. Eles são utilizados para prevenir que pacientes de risco desenvolvam doenças cardiovasculares, como o infarto agudo do miocárdio (IAM) ou o acidente vascular cerebral (AVC). Por serem muito utilizados, constantemente o cirurgião-dentista poderá se deparar em sua rotina clínica, com pacientes usuários de anticoagulantes ou antiagregantes. Neste caso, o profissional precisará estar ciente das normas mais atuais de manejo com cada um dos tipos de medicamentos, para que o tratamento seja realizado com sucesso. No presente trabalho, é proposto um Protocolo Operacional Padrão (POP), que pode ser seguido no momento de realizar cirurgias orais em pacientes em uso de Varfarina, Ácido Acetil Salicílico, Heparina de Baixo Peso Molecular, Heparina Não Fracionada, Rivaroxabana e Clopidogrel.

Anticoagulants and antiplatelet agents are drugs used by a large portion of the world population. They are used to prevent at-risk patients from developing cardiovascular diseases, such as acute myocardial infarction (AMI) or stroke (stroke). Because they are widely used, the dental surgeon may constantly encounter patients using anticoagulants or anti-aggregating agents in their clinical routine. In this case, the professional will need to be aware of the most current management standards with each type of medication, so that the treatment is carried out successfully. In the present work, a Standard Operational Protocol (POP) is proposed, which can be followed when performing oral surgeries on patients using Warfarin, Acetyl Salicylic Acid, Low Molecular Weight Heparin, Unfractionated Heparin, Rivaroxaban and Clopidogrel.

Intervenção coronária percutânea no paciente com alto risco de hemorragia / Percutaneous coronary intervention in the patient at high risk of bleeding

Na atualidade, as intervenções coronárias percutâneas são responsáveis por mais de 80% dos procedimentos de revascularização miocárdica. Esse resultado é possível por dois grandes avanços: o desenvolvimento de stents farmacológicos eficazes e seguros, somado a uma farmacoterapia antitrombótica potente e efetiva na prevenção de eventos aterotrombóticos, a qual, em geral, deve ser mantida por cerca de 6 a 12 meses após a intervenção índice. No entanto, expressivo contingente de casos, que a literatura situa em até 20% dos pacientes tratados, apresenta risco para desenvolver hemorragias significantes, que podem ter grave impacto no prognóstico. Assim, essa população requer uma série de cuidados relacionados com a indicação, a realização e o acompanhamento tardio. O processo se inicia pela identificação dos casos mais predispostos, o que, na maior parte das situações, é simples, havendo inclusive escores de risco que auxiliam o car­ diologista. Na sequência, a indicação do procedimento deve ser feita com propriedade. Os cuidados são iniciados pela prescrição preferencial do clopidogrel ao invés dos demais inibidores da P2Y12; no momento do procedimento, sempre que viável, a opção pela via radial é vantajosa, em especial em síndromes coronárias agudas. O uso de um modelo de stent com liberação de medicamentos também é recomendado nesses casos, pois os stents contemporâneos são seguros a ponto de permitirem a abreviação com segurança do tempo de uso do esquema antiplaquetário duplo. Por fim, mais recentemente, tem sido discutida a monoterapia com inibidores do receptor P2Y12, na qual a suspensão precoce do ácido acetilsalicílico não comprometeria a segurança e, ao mesmo tempo, seria capaz de prevenir eventos hemorrágicos de vulto.

Currently, percutaneous coronary interventions account for more than 80% of myocardial revascularization procedures. This result was enabled by two major advances: the development of effective and safe drug­eluting stents, in addition to a potent and effective antithrombotic pharmacotherapy in the prevention of atherothrombotic events, which, in general, should be maintained for about 6 to 12 months after the index intervention. However, a significant number of cases (up to 20% of treated patients according to literature) are at risk for developing significant bleeding, which can have a serious impact on prognosis. Therefore, this population requires a series of care measures related to indication, performance of the procedure, and late follow­up. The process begins with the identification of the most predisposed cases, which, in most situations, is simple, and there are risk scores that help the cardiologist. Next, the indication of the procedure should be done appropriately. Care begins with the preferential prescription of clopidogrel instead of other P2Y12 inhibitors; at the time of the procedure, whenever feasible, the option for the radial access is advantageous, especially in acute coronary syndromes. The use of a drug­eluting stent is also recommended in these cases, since contemporary stents are safe enough to safely shorten the duration of use of the dual antiplatelet regimen. Finally, more recently, monotherapy with P2Y12 receptor inhibitors has been discussed, in which early withdrawal of acetylsalicylic acid would not compromise safety and, at the same time, it would be able to prevent major bleeding events.

The analysis on the correlation between CYP2C19 gene polymorphism and clopidogrel resistance in patients with acute coronary syndrome / 中国医师进修杂志

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.

Preparation of active thiol metabolite of clopidogrel by isolated rat liver perfusion / 中国药房

OBJECTIVE To estab lish the pre paration method of clopidogrel active thiol metabolite （CATM），and to provide reference for the synthesis of cis-CATM. METHODS CATM was prepared ，separated and purified with isolated rat liver perfusion and ChromCore 120 C18 preparative column ，using（S）-2-oxo-clopidogrel as substrate. The target compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The retention time of the active configuration of CATM in the human body （cis-CATM）were compared to confirm the proportion of active configuration in the target product. RESULTS The conversion rate of the target product was 11.71％. The target products were identified as CATM by MS and 1H-NMR. Peak 2-peak 5 of CATM were four stereoisomers. The retention time of them were 21.3，22.3，26.5，27.3 min. The peak area ratios of them were 7.13％，7.23％，63.52％，14.97％，respectively. Based on that retention time of the active configuration of CATM in human body was 26.3 min，the active cis-stereoisomer in the target product CATM accounted for 63.52％. CONCLUSIONS This method is low-cost ，simple，and can prepare CATM with higher active configuration.

Ticagrelor combined with atorvastatin for the treatment of unstable angina pectoris / 中国基层医药

Objective:To investigate the efficacy of ticagrelor combined with atorvastatin in the treatment of unstable angina pectoris and its effects on cardiac function, brain natriuretic peptide (BNP) level, lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, and glycosylated hemoglobin (HbAlc) level in patients with unstable angina pectoris.Methods:A total of 200 patients with unstable angina pectoris who received treatment in the Sahzu International Medical Center from January 2017 to January 2019 were included in this study. These patients were randomly assigned to receive either clopidogrel combined with atorvastatin (control group, n = 100) or ticagrelor combined with atorvastatin (observation group, n = 100) for 1 month. The clinical efficacy,BNP level, Lp-PLA2 activity, HbAlc level, clinical symptom, cardiac function, and adverse reactions were compared between control and observation groups. Results:Effective rate was significantly higher in the observation group than in the control group [95% (95/100) vs. 75% (75/100), χ2 = 15.69, P < 0.001]. After treatment, BNP level and Lp-PLA2 activity in the observation group were (101.21 ± 40.13) ng/L and (105.56 ± 12.56) pg/L, respectively, which were significantly lower than those in the control group [(151.57 ± 37.29) ng/L, (137.52 ± 16.88) pg/L, t = 9.19, 15.19, P < 0.001]. After treatment, the duration and frequency of angina pectoris in the observation group were (1.84 ± 0.49) minutes/time and (1.32 ± 0.21) times/week, respectively, which were significantly lower than those in the control group [(5.23 ± 1.72) minutes/time and (3.58 ± 0.71) times/week, t = 18.95, 30.52, both P < 0.001]. After treatment, the left ventricular end-diastolic diameter and left ventricular end-systolic diameter in the observation group were (33.28 ± 1.21) mm and (47.89 ± 5.61) mm respectively, which were significantly lower than those in the control group [(37.56 ± 2.14) mm, (53.25 ± 5.07) mm, t = 17.41, 7.09, both P < 0.001]. Left ventricular ejection fraction was significantly higher in the observation group than in the control group [(48.59 ± 5.81)% vs. (41.16 ± 5.83)%, t = 9.03, P < 0.001]. The incidence of adverse reactions was significantly higher in the observation group than in the control group [1% (1/100) vs. 12% (12/100), χ2 = 9.96, P = 0.002]. Conclusion:Ticagrelor combined with atorvastatin is highly effective for unstable angina pectoris in coronary heart disease because it greatly decreases BNP level and Lp-PLA2 activity. Therefore, the combined therapy deserves clinical promotion.

Relationship between clopidogrel responsiveness and CYP2C19 genotype by thromboelastography in patients with coronary heart disease after PCI / 中国输血杂志

【Objective】 To explore the relationship between clopidogrel responsiveness and CYP2C19 gene polymorphism by thromboelastography(TEG) after PCI in patients with coronary heart disease, and its guiding significance for the use of clopidogrel after PCI. 【Methods】 A total of 246 patients who underwent PCI surgery in our hospital from June 2018 to May 2021 and routinely took clopidogrel maintenance treatment after the operation were selected.The platelet inhibition rate of the patients was detected by TEG to obtain their response to clopidogrel.The CYP2C19 genotype was detected, and the relationship between the patient′s responsiveness to clopidogrel and the CYP2C19 genotype was analyzed. 【Results】 The CYP2C19 genotypes in 246 patients were fast metabolizer (n=95), intermediate metabolizer (n=104) and slow metabolizer (n=47), with the mean ADP inhibition rate(%) at 46.27±21.41, 40.99±25.53 and 24.77±21.68, respectively.They were divided into clopidogrel resistant group (n=98) and clopidogrel normal response group (n=148). The three groups of patients with different CYP2C19 genotypes had no statistically significant differences in gender composition, age and platelet count (P>0.05), while significant differences in hypertension, diabetes and hyperlipidemia(P0.05), but they were all lower than those with slow metabolism patients (both P0.5). Statistically significant difference was noticed in the low responsiveness to clopidogrel by different CYP2C19 genotypes (P<0.05). The drug responsiveness of clopidogrel measured by TEG had strong correlation with the patient′s CYP2C19 genotype.When the ADP inhibition rate was the best cut-off value (27.10%), the sensitivity and specificity of CYP2C19 genotype being diagnosed as the slow metabolite type, was 73.37% and 70.21%, respectively. 【Conclusion】 The response of clopidogrel after PCI in patients with coronary heart disease is associated with CYP2C19 genotype polymorphism.The use of TEG to detect the ADP inhibition rate of patients has strong predictive effect on CYP2C19 genotype and has guiding significance on antiplatelet therapy in patients with coronary heart disease after PCI.

Estrategias de antiagregación en síndromes coronarios agudos sin elevación del segmento ST / Antiplatelet Strategies in Non-ST-Segment Elevation Acute Coronary Syndrome

RESUMEN Introducción: Existe información limitada sobre estrategias de tratamiento con inhibidores del receptor P2Y12 (iP2Y12) en síndromes coronarios agudos sin elevación del segmento ST (SCASEST) en la vida real. Objetivos: Determinar la incidencia de eventos cardíacos adversos mayores (MACE)y sangrado BARC ≥2, según la estrategia de tratamiento con iP2Y12 a 6 meses. Material y métodos: Subanálisis preespecificado del registro BUENOS AIRES I (n = 1100). Se estratificó la cohorte según "pretratamiento" con iP2Y12 (antes de conocer la anatomía coronaria), o "tratamiento en sala" (luego de conocer la anatomía coronaria) y se analizó la incidencia de eventos clínicos, según: pretratamiento con clopidogrel/ticagrelor, tratamiento en sala con clopidogrel/ticagrelor. Resultados: La edad media fue 65,4 ± 11,5 años, con 77,2% de sexo masculino. El 79,72% recibió iP2Y12, el 75% como pretratamiento y 25% como tratamiento en sala. Los pacientes con pretratamiento fueron más jóvenes y con más infarto agudo de miocardio (IAM), en comparación con el subgrupo de tratamiento en sala. A los 6 meses, no hubo diferencias significativas en la incidencia de MACE (16,4% vs. 14,4%; p = 0,508), o sangrado BARC ≥2 (14,7% vs. 11,1%; p = 0,205), entre los distintos momentos de administración del iP2Y12. El tratamiento con ticagrelor presentó menos MACE en comparación con el clopidogrel (p = 0,044), sin diferencias en sangrados. No se observaron diferencias en MACE entre ticagrelor en pretratamiento o tratamiento en sala (p = 0,893). Conclusiones: El subgrupo de pacientes seleccionados para recibir pretratamiento con iP2Y12 no presentó diferencias en MACE ni sangrado en relación con los tratados en sala. Los pacientes seleccionados para su tratamiento con ticagrelor en sala presentaron un balance beneficioso entre eventos isquémicos y hemorrágicos.

ABSTRACT Background: There is limited real life information on treatment strategies with P2Y12 receptor inhibitors (P2Y12i) in nonST-segment elevation acute coronary syndromes (NSTEACS). Objectives: The aim of this study was to determine the incidence of major adverse cardiac events (MACE) and BARC bleeding ≥2, according to the treatment strategy with P2Y12i at 6 months. Methods: The study used the pre-specified subanalysis of the BUENOS AIRES I registry (n=1100). The cohort was stratified according to P2Y12i "pretreatment" (before knowing the coronary anatomy), or "ward treatment" (after knowing the coronary anatomy), and the incidence of clinical events was analyzed according to pretreatment or ward treatment with clopidogrel/ ticagrelor. Results: Mean age was 65.4 ± 11.5 years and 77.2% were male patients. In 79.72% of cases patients received P2Y12i, 75% as pretreatment and 25% as ward treatment. Pretreatment patients were younger and with greater prevalence of acute myocardial infarction (AMI) compared with the ward treatment subgroup. At 6 months, there were no significant differences in the incidence of MACE (16.4% vs. 14.4%; p = 0.508), or BARC bleeding ≥2 (14.7% vs. 11.1%; p = 0.205), between the different times of P2Y12i administration. Treatment with ticagrelor presented reduced MACE compared with clopidogrel (p = 0.044), with no difference in bleeding. No MACE differences were observed between pretreatment or in ward treatment with ticagrelor (p=0.893). Conclusions: The subgroup of patients selected to receive P2Y12i pretreatment did not present differences in MACE or bleeding relative to those treated in ward. Patients selected for ticagrelor treatment in ward presented a beneficial balance between ischemic and hemorrhagic events.

Acercamiento a la terapia antiplaquetaria en el contexto de la endoscopia digestiva / Approach to antiplatelet therapy in the context of digestive endoscopy

Introducción: El empleo de agentes antiagregantes plaquetarios se ve cada día más extendido en la población mundial. La decisión en relación al manejo endoscópico de este tratamiento debe estar basada en el tipo de indicación médica que justifica el uso de estos medicamentos. Se realizó una revisión de los artículos publicados en las bases de datos Pubmed, Scielo, Medline y Cochrane, relacionados con el tema. Objetivo: Profundizar en los conocimientos relacionados con la terapia antiplaquetaria periendoscópica digestiva. Desarrollo: Los antiagregantes plaquetarios son clave en el tratamiento y prevención de eventos trombóticos vasculares, cardíacos o cerebrales. Se han establecido las indicaciones de los antitrombóticos, también se ha evaluado el riesgo tromboembólico al suspender el tratamiento. El riesgo tromboembólico puede ser bajo o alto, por lo que se debe evaluar el riesgo - beneficio de suspender la terapia en este contexto. Todos los procedimientos endoscópicos presentan un riesgo de hemorragia, se considera el bajo riesgo de sangrado por debajo del 1 y alto riesgo por encima del 1 por ciento. La decisión acerca de la antiagregación en el periodo perioperatorio/ periprocedimiento, no solo depende del balance entre el riesgo trombótico y hemorrágico, sino también del tipo y la indicación del tratamiento antiplaquetario. Conclusiones: La antiagregación plaquetaria en pacientes que serán sometidos a procederes gastrointestinales intervencionistas se observa cada vez con mayor frecuencia. Esto hace necesario el conocimiento acerca de la valoración del riesgo de fenómenos trombóticos al interrumpir estos fármacos, junto con la determinación del riesgo potencial de sangrado según el procedimiento endoscópico realizado(AU)

Introduction: The use of platelet antiaggregant agents is increasingly widespread in the world population. The decision regarding the endoscopic management of this treatment should be based on the type of medical indication that justifies the use of these medications. A review of the articles published in the Pubmed, Scielo, Medline and Cochrane databases related to the subject was made. Objective: To deepen the knowledge related to periendoscopic digestive antiplatelet therapy. Development: Platelet antiaggregant are key in the treatment and prevention of vascular, cardiac or cerebral thrombotic events. Just as the indications of antithrombotic agents have been established, the thromboembolic risk has also been evaluated when treatment is suspended. The thromboembolic risk may be low or high, so the risk-benefit of discontinuing therapy in this context should be evaluated. All endoscopic procedures present a risk of bleeding considering the low risk of bleeding below 1 percent and high risk above 1 percent. The decision about anti-aggregation in the perioperative / periprocedural period depends not only on the balance between thrombotic and hemorrhagic risks, but also on the type and indication of antiplatelet therapy. Conclusions: Platelet anti-aggregation in patients who will undergo interventional gastrointestinal procedures is observed more and more frequently. This makes knowledge about the risk assessment of thrombotic phenomena necessary when interrupting these drugs, together with the determination of the potential risk of bleeding according to the endoscopic procedure performed(AU)