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.

Safety and efficacy of short-term dual antiplatelet therapy combined with intensive rosuvastatin in acute ischemic stroke

Abstract Objective: To investigate the safety and efficacy of short-term (7-day) Dual Antiplatelet Therapy (DAPT) with intensive rosuvastatin in Acute Ischemic Stroke (AIS). Methods: In this study, patients with AIS in the emergency department of the hospital from October 2016 to December 2019 were registered and divided into the control group (Single Antiplatelet Therapy [SAPT] + rosuvastatin) and the study group (7-day DAPT + intensive rosuvastatin) according to the therapy regimens. The generalized linear model was used to compare the National Institute of Health Stroke Scale (NIHSS) scores between the two groups during the 21-day treatment. A Cox regression model was used to compare recurrent ischemic stroke, bleeding events, Statin-Induced Liver Injury (SILI), and Statin-Associated Myopathy (SAM) between the two groups during the 90-day follow-up. Results: Comparison of NIHSS scores after 21-day treatment: NIHSS scores in the study group decreased significantly, 0.273-times as much as that in the control group (Odds Ratio [OR] 0.273; 95% Confidence Interval [95% CI] 0.208-0.359; p < 0.001). Comparison of recurrent ischemic stroke during the 90-day follow-up: The therapy of the study group reduced the risk of recurrent stroke by 65% (7.76% vs. 22.82%, Hazard Ratio [HR] 0.350; 95% CI 0.167-0.730; p = 0.005). Comparison of bleeding events: There was no statistical difference between the two groups (7.79% vs. 6.71%, HR = 1.076; 95% CI 0.424-2.732; p = 0.878). No cases of SILI and SAM were found. Conclusions: Short-term DAPT with intensive rosuvastatin effectively relieved the clinical symptoms and significantly reduced the recurrent stroke for patients with mild-to-moderate AIS within 90 days, without increasing bleeding events, SILI and SAM.

Positioning of the fixed dose combination of Rosuvastatin + Clopidogrel + Aspirin in the Treatment of Cardiovascular Diseases

Dual anti-platelet therapy (DAPT) and statins are recommended by guidelines for the management of cardiovascular diseases (CVDs), even though the duration of treatment is guided by ischemic and bleeding risk. Clopidogrel and aspirin are the most commonly used DAPT in CVDs. Adding a statin to DAPT is helpful in reducing the thrombosis risk. Fixed-dose combination (FDC) therapy in CVD can help to address the factors of convenience, compliance, control, cost, and complication better than free drug combinations. Therefore, the FDC of rosuvastatin (10 mg or 20 mg) + clopidogrel (75 mg) + aspirin (75 mg) is likely to improve compliance in CVD patients, thereby reducing adverse cardiovascular outcomes and cost of treatment. There is lack of awareness on long term benefits of this FDC in Indian patients.

Endoprótesis coronaria y doble terapia antiplaquetaria prolongada. Un estudio longitudinal / Coronary stent and prolonged dual antiplatelet therapy. A longitudinal study

Resumen Introducción: En las guías actuales europeas para el manejo del infarto de miocardio posterior a la colocación de endoprótesis coronaria (stent), no existe consenso sobre la duración ideal de la terapia antiagregante plaquetaria dual (DAPT, dual antiplatelet therapy) para prevenir la trombosis-reestenosis del stent sin aumentar el riesgo significativo de sangrado. Objetivo: Reportar el porcentaje de sangrado mayor y de eventos cardiovasculares mayores asociados a la DAPT prolongada en pacientes atendidos en el Instituto Nacional de Cardiología y tratados con intervención coronaria percutánea primaria y stent. Métodos: Se realizó un estudio longitudinal, prospectivo observacional y descriptivo no experimental. Los pacientes fueron captados de noviembre de 2016 a diciembre de 2017. Resultados: Fueron seleccionados 135 pacientes con una media de edad de 57 ± 10 años, quienes cumplieron un seguimiento clínico por tres años. La obesidad y la hipertensión destacaron como principales factores de riesgo. Posterior al uso de DAPT durante tres años, se registró 3.7 % de mortalidad, 1.48 % de sangrado mayor y 4.4 % de trombosis-reestenosis. Conclusiones: El uso prolongado de DAPT estaría justificado por la alta incidencia de trombosis-reestenosis, sin incremento significativo en el riesgo de sangrado y con disminución de los eventos cardiovasculares mayores.

Abstract Introduction: In current European guidelines for the management of myocardial infarction after coronary stent placement, there is no consensus on dual antiplatelet therapy (DAPT) ideal duration to prevent stent thrombosis-restenosis without significantly increasing the bleeding risk. Objective: To report the percentage of major bleeding and presence of major cardiovascular events associated with prolonged DAPT in patients recruited at the National Institute of Cardiology, treated with primary percutaneous coronary intervention and stent. Methods: A longitudinal, prospective, observational, non-experimental, descriptive study was carried out. Patients were recruited from November 2016 to December 2017. Results: One-hundred and thirty-five patients with a mean age of 57 ± 10 years who completed the three-year follow-up were selected. Obesity and hypertension stood out as the main risk factors. After using DAPT for three years, 3.7% of mortality, 1.48% of major bleeding, and 4.4% of thrombosis-restenosis were recorded. Conclusions: Prolonged use of DAPT would be justified by the high incidence of thrombosis-restenosis, without a significant increase in bleeding risk, as well as a decrease in major cardiovascular events.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

The clinical profile of patients with intracerebral hemorrhage after receiving acute coronary syndrome regimen in a tertiary hospital: A case series

@#Coronary heart disease, which includes acute coronary syndromes (ACS) is a major cause of death and morbidity. Treatment for this condition includes dual anti-platelet treatment combined with an anti-coagulant and an anti-dyslipidemic. Bleeding complications may occur and one fatal adverse event is intracerebral hemorrhage (ICH). ACS cases in a tertiary hospital for the years 2014-2018 showed that there were 7 patients who presented with symptomatic ICH after treatment administration that accounts for 0.01% of a total of 1,097 patients. These patients were over the age of 50, but with no sex predilection. Common comorbidities were hypertension and malignancy. All patients presented with acute onset neurologic deficits within 1-4 days after administration of ACS regimen, with ICH scores of 3-4 signifying a high mortality rate of 72-90%. 6 out 7 patients had significant volume of ICH with mass effects, and 1 with subarachnoid hemorrhage. This lead to poor outcome in all patients with 6 out of 7 mortalities and 1 left with substantial disability. It was found that given the total number of patients administered with the said treatment, there is a low incidence of ICH.

Comparison of short-term and long-term dual antiplatelet therapy after implantation of drug-eluting stents—Meta analysis / 药学实践杂志

Objective To evaluate the clinical effects of short-term (3-6 months) and long-term (12 months) dual antiplatelet therapy (DAPT) after the implantation of coronary drug-eluting stents (DES). Methods The eligibilities of the patients included stable angina, acute coronary syndrome and silent ischemia. The lesions were in a native coronary vessel. The clinical observation endpoints were all-cause death, cardiogenic death, myocardial infarction, stroke, stent thrombosis, target lesion revascularization, severe bleeding, and true adverse clinical events. The clinical observation endpoints were all-cause death, cardiogenic death, myocardial infarction, stroke, stent thrombosis, target lesion revascularization, severe bleeding, and true adverse clinical events. By searching Pubmed, Chinese biomedical literature and other Chinese and English databases and manual search, qualified randomized controlled studies were evaluated and data were extracted for meta-analysis. Results A total of 12 randomized controlled studies were conducted. Detsky scores were all greater than 5 points. There were a total of 25949 patients in the study with a follow-up rate of 97.9%. There were no significantly different in all cause death (OR = 0.86，95%CI 0.71-1.05，P = 0.14), cardiac death (OR = 0.94，95% CI 0.70-1.25，P = 0.67), stent thrombosis (OR = 1.36，95%CI 0.94-1.98，P = 0.11), stroke (OR = 1.01，95%CI 0.71-1.42，P = 0.98), target lesion revascularization (OR = 0.121，95%CI 0.94-1.55，P = 0.14),and true adverse clinical events (OR = 0.98，95%CI 0.83-1.14，P = 0.75). The incident rate of myocardial infarction during the follow-up period was higher in the short-term group than in the long-term group (OR = 1.27, 95% CI 1.02-1.59, P = 0.04). The proportion of severe bleeding in the long-term group increased significantly (OR = 0.69, 95% CI 0.50-0.95, P = 0.02). Asian population studies showed that all-cause mortality was higher in the long-term treatment group than in the short-term group (OR = 0.72, 95% CI 0.53-0.97, P = 0.03), and there was no significant difference in severe bleeding between the two groups. Conclusion According to the defined clinical observation endpoints, the short-term dual antiplatelet effect is not inferior to the long-term group. Seven asian group studies have shown that the long-term group has high all-cause mortality. It can not rule out the deviation and/or population caused by the small sample size or individual variation. The results need to be further verified. This result can be used as a clinical warning to adjust the dual antiplatelet cycle based on the individualized risk of bleeding and coronary lesions.

Analysis of premature ticagrelor discontinuation in patients with acute coronary syndrome during dual antiplatelet therapy / 第二军医大学学报

Objective To explore the incidence, causes and influencing factors of premature ticagrelor discontinuation (PTD) in patients with acute coronary syndrome (ACS). Methods A total of 400 hospitalized ACS patients who were treated with aspirin and ticagrelor in the Department of Cardiovasology, Changhai Hospital, Naval Medical University (Second Military Medical University) from Jan. to Oct. 2018 were retrospectively enrolled. Baseline data were collected and patients were followed up to analyze the incidence, causes and influencing factors of PTD in ACS patients. Results At 12 months after discharge, PTD occurred in 49 patients (12.2%), and was free in 351 patients (87.8%). The proportions of patients with age>75 years, heart failure history or previous percutaneous coronary intervention (PCI) and the levels of serum potassium and urea in PTD group were significantly higher than those in non-PTD group (P=0.004, 0.031, 0.028, 0.037, 0.001). The proportion of patients using β-blocker and the severity of vascular stenosis in PTD group were significantly lower than those in non-PTD group (P=0.041, 0.018). Dyspnea (22.4%, 11/49), drug unavailability (18.4%, 9/49) and bleeding (12.2%, 6/49) were the three most common causes of PTD. PTD occurred in all dyspnea patients with modified British Medical Research Council (mMRC) being grade 2 or higher (two cases with grade 1, six cases with grade 2, two cases with grade 3, and one case with grade 4). Kaplan-Meier curve analysis showed that 67.3% (33/49) of patients with PTD occurred within 90 days after discharge. Multivariate logistic regression analysis showed that age>75 years old (odds ratio [OR]=2.58, 95% confidence interval[ CI] 1.26-5.26, P=0.009) and elevated urea (OR=1.17, 95% CI 1.04-1.30, P=0.007) were independent predictors of PTD in ACS patients, while severity of vascular stenosis (OR=0.95, 95% CI 0.92-0.98, P=0.001) was the related factor of adherence to ticagrelor. Conclusion The incidence of PTD in ACS patients during dual antiplatelet therapy is 12.2%. For dyspnea patients with mMRC score of grade 2 or higher, P2Y12 receptor antagonist should be replaced in time. Age> 75 years old is an independent predictor of PTD in ACS patients and more attention is needed for elderly patients taking ticagrelor whether they have dyspnea or PTD.

Diferencias en el tratamiento antitrombótico y pronóstico en función del sexo en pacientes con síndrome coronario agudo tratados con stent / Sex-specific differences in antithrombotic therapy and prognosis in patients with acute coronary syndrome treated with stent

Resumen Antecedentes y objetivo: El interés sobre la influencia del sexo en pacientes con síndrome coronario agudo (SCA) tratados con stent y nuevos antiagregantes inhibidores de P2Y12 en la práctica clínica es creciente. Se analizan las diferencias en función del sexo en el tratamiento con doble antiagregación plaquetaria (DAPT) y los eventos adversos isquémicos y hemorrágicos Materiales y métodos: Estudio prospectivo de pacientes consecutivos con diagnóstico de SCA tratados con stent coronario desde julio de 2015 hasta enero de 2016. Resultados: De un total de 283 pacientes incluidos, 75 (26.5%) correspondió a mujeres y 208 (73.5%) a hombres. La edad media fue de 71 ± 13 y 66.5 ± 13 años, respectivamente. Un 44% de mujeres se presentó como SCA con elevación del segmento ST contra un 52.4 de los hombres, p = 0.21. Las mujeres mostraron un mayor riesgo de sangrado (CRUSADE), sin diferencias en el riesgo isquémico (GRACE y TIMI). Se usaron stents farmacoactivos con más frecuencia en mujeres (88.9 vs. 75.5%, p = 0.04). Se observó una tendencia de menor prescripción del ticagrelor en mujeres (42.6 vs. 50.9%, p = 0.29) en favor de un mayor uso del clopidogrel. No se identificaron diferencias en cuanto a la prescripción del prasugrel. Las mujeres presentaron al año una menor mortalidad (1.4 vs. 6.7%, p = 0.19), aunque mayor sangrado (23.3 vs. 17.4%, p = 0.27). Conclusiones: En este estudio de pacientes consecutivos con SCA tratados con stent se registró una mayor prescripción de clopidogrel en las mujeres que en los hombres. Las mujeres presentaron una menor incidencia anual de mortalidad, pero mayor sangrado en comparación con los hombres, no significativo.

Abstract Aims and objective: Impact of sex-related differences in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention and treated with new P2Y12 inhibitors is not adequately characterised. We aimed to analyse gender-based differences in dual antiplatelet therapy, and adverse cardiovascular events and bleeding. Materials and methods: Prospective-observational study of the consecutive ACS patients treated with stent from July 2016 to January 2016, with a follow-up of 1 year. Results: We examined 283 patients, 75 (26.5%) women and 208 (73.5%) men. Women were older than men (71 ± 13 vs. 66,5 ± 13 years). There were 44% of women and 52% of men presenting with ST-elevation ACS (p = 0.21). Women had a higher bleeding risk (CRUSADE), without differences in the ischaemic risk (GRACE and TIMI). More women were treated with drug-eluting stent (88.9 vs. 75.5%, p = 0.04). There was a lower rate of ticagrelor prescription in women (42.6 vs. 50.9%, p = 0.29), in favour of clopidogrel. No differences were observed in prasugrel prescription. No significant differences were observed after a year of follow up, but women had a tendency towards lower mortality (1.4 vs. 6.7%, p = 0.19) and higher bleeding rates (23.3 vs. 17.4%, p = 0.27). Conclusions: In our study of patients presenting with ACS treated with stent, clopidogrel was preferred in women, whereas ticagrelor was the most frequent prescription in men. No significant differences were noted in clinical outcomes, but women experienced a tendency towards less mortality and more bleeding events.

Meta-analysis on safety and efficacy of dual antiplatelet therapy combining with proton pump inhibitors for patients after percutaneous coronary intervention / 中华心血管病杂志

Objective@#To analyze the impact of dual antiplatelet (DAPT) therapy combining with or without proton pump inhibitors (PPI) on the main outcomes after percutaneous coronary intervention (PCI).@*Methods@#The PubMed, EMBASE and Cochrane Library were searched for relevant literature and the references obtained from these sources were retrieved manually from inception till September 2017. Inclusion and exclusion criteria were established follow the Cochrane review standard. A total of 977 literatures were included, 193 duplicates were excluded, 74 reviews, case reports, letters and systematic reviews were excluded, 667 literatures were excluded after reading the title and abstract, 34 literatures were excluded due to non-randomized control studies and unrelated outcome indicators, and 9 literatures were finally included with a total of 16 589 patients. RevMan 5.3 software was used to compare the incidence of major adverse cardiovascular events (MACE), cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis, stroke, gastrointestinal bleeding and gastrointestinal events in patients with DAPT combining with or without PPI after PCI.@*Results@#MACE was observed in 8 out of the 9 included literatures, and the results showed that MACE occurred in 561 out of 6 282 patients receiving DAPT combining with PPI therapy and in 951 out of 9 632 patients using DAPT alone (OR=1.15, 95%CI 0.88-1.51, P>0.05). Cardiogenic death was observed in 7 out of the 9 included literatures, and the results showed that cardiogenic death occurred in 172 out of 6 453 patients receiving DAPT combining with PPI treatment and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Recurrent myocardial infarction was observed in 7 out of the 9 included literatures, the results showed 416 out of 6 282 cases in DAPT combining with PPI therapy group experienced recurrent myocardial infarction and 691 out of 9 632 cases in DAPT group experienced recurrent myocardial infarction (OR=1.01, 95%CI 0.89-1.16, P>0.05). Four out of 9 literatures observed revascularization. The results showed that revascularization was performed in 64 out of 2 173 patients receiving DAPT combining with PPI therapy and in 105 out of the 2 770 patients using DAPT alone (OR=1.33, 95%CI 0.55-3.24, P>0.05). All-cause death was observed in 7 out of the 9 included literatures, and the results showed that all-cause death occurred in 172 out of the 6 453 patients in DAPT combining with PPI therapy group and in 321 out of the 9 839 patients using DAPT alone (OR=0.97, 95%CI 0.80-1.18, P>0.05). Three out of the 9 included articles observed stent thrombosis, and the results showed that stent thrombosis occurred in 99 out of 2 997 patients receiving DAPT combining with PPI therapy and in 245 out of the 6 198 patients treated with DAPT (OR=1.07, 95%CI 0.83-1.37, P>0.05). Stroke was observed in 2 out of the 9 included literatures. The results showed that stroke occurred in 5 out of 2 019 patients receiving DAPT combining with PPI therapy, and in 4 out of the 2 033 patients treated with DAPT (OR=1.00, 95%CI 0.29-3.49, P>0.05). Gastrointestinal bleeding was observed in 6 out of the 9 included literatures. The results showed that gastrointestinal bleeding occurred in 26 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 93 out of the 3 506 patients treated with DAPT, gastrointestinal bleeding was significantly lower in the DAPT combining with PPI group than DAPT alone group (OR=0.27, 95%CI 0.17-0.41, P<0.01). Gastrointestinal events were reported in 6 out of the 9 included articles. Similarly, gastrointestinal events were observed in 51 out of 3 517 patients receiving DAPT combined with PPI therapy, and in 190 out of the 3 506 patients treated with DAPT alone, the incidence of gastrointestinal events in the DAPT combined with PPI group was significantly lower than DAPT alone group (OR=0.24, 95%CI 0.14-0.42, P<0.01).@*Conclusions@#The incidence of MACE, cardiogenic death, recurrent myocardial infarction, target vessel revascularization, all-cause death, stent thrombosis and stroke are not affected by DAPT combined with PPI therapy after PCI, while the incidence of gastrointestinal bleeding and gastrointestinal events could be reduced by adding PPI to DAPT in patients undergoing PCI.

Effects of Dual-antiplatelet Medication Time on Efficacy and Safety of Postoperative Complications after Transcatheter Aortic Valve Implantation ：A Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the effects of dual-antiplatelet medication time on efficacy and safety of postoperative complications after transcatheter aortic valve implantation （TAVI）， and to provide evidence-based reference for the formulation of antiplatelet therapy after TAVI. METHODS： Retrieved from Cochrane clinical controlled trial registration center， PubMed， Embase， Web of Science， Wanfang database and CJFD， during database establishment to Feb. 2019， RCTs and observational study about efficacy （all-cause mortality and incidence of stroke） and  safety （the incidence of major bleeding events） the effects of dual-antiplatelet therapy for postoperative complications after TAVI at different time points were collected. After data extraction of clinical studies met inclusion criteria， quality evaluation with Cochrane bias risk evaluation tool 5.1.0 （for RCT） or Newcastle- Ottawa Scale （for observational study）， Meta-analysis was conducted by using Rev Man 5.3 and Stata 14.0 statistical software. Meta-regression analysis was also conducted for outcome and different treatment duration. RESULTS： A total of 3 RCTs and 10 observational studies were included， involving 2 868 patients. The results of Meta-analysis showed that the incidence of all-cause mortality one month and 6 months after medication were 0.05 [95％CI （0.03， 0.07）， P＜0.001] and 0.07 [95％CI （0.05， 0.08）， P＜0.001]. The incidence of major bleeding events 1， 3 and 6 months after medication were 0.14 [95％CI （0.08，0.19）， P＜0.001]， 0.11 [95％CI （0.03， 0.19）， P＝0.007] and 0.13 [95％CI （0.05， 0.22）， P＝0.002]. The incidence of stroke after one month after medication was 0.04 [95％CI （0.03， 0.05）， P＜0.001]. Results of Meta-regression analysis showed that the all-caused mortality [regression coefficient＝0.005 7， 95％CI （－0.001 6， 0.013 0）， P＝0.116]， major bleeding [regression coefficient＝－0.000 5，95％CI（－0.022 4，0.021 4）， P＝0.959] or the incidence of stroke [regression coefficient＝0.001 4， 95％CI （－0.003 8， 0.006 5）， P＝0.570] were not related to medication duration of dual-antiplatelet therapy.  CONCLUSIONS： The prolongation of the medication time of the dual-antiplatelet therapy has no significant effect on the efficacy and safety of TAVI.

A study on platelet reactivity and associated clinical characteristics in acute coronary syndrome patients treated with Ticagrelor and Clopidogrel

Background: The pathophysiology of the acute coronary syndrome (ACS) is characterized by the rupture of an atherosclerotic plaque within the coronary artery, with subsequent platelet aggregation, thrombus formation, and ischemia. Before platelets aggregate, they must first be activated to express activated glycoprotein IIb/IIIa receptors on the cell surface. This activation is the result of stimulation from endogenous platelet agonists, such as thromboxane A2 and adenosine diphosphate (ADP). ADP activates platelets by binding to P2Y12 receptors on the cell surface. Despite clinical efficacy in a broad range of coronary artery disease patients, pharmacodynamic studies conducted in patients undergoing stenting showed that clopidogrel therapy was associated with variable and moderate platelet inhibition (50% inhibition at steady state as demonstrated by ex-vivo ADP-induced platelet aggregation) as well. Ticagrelor, a cyclopentyl-triazolo-pyrimidine acting as an analog of adenosine triphosphate (ATP), constitutes a first non-thienopyridine direct platelet P2Y12 receptor blocker. Aim of the study: To investigate factors linked to HOTPR on ticagrelor and whether they differ from factors linked to HOTPR on clopidogrel. Materials and methods: Totally 300 patients were included in the study Patients presenting to the Department of Cardiology, SRM Medical College Hospital and Research Institute, Kattangulathur, Veeraraghavan Sriram, Venkatesh Munusamy, Dhandapani Vellala Elumalai. A study on platelet reactivity and associated clinical characteristics in acute coronary syndrome patients treated with Ticagrelor and Clopidogrel. IAIM, 2019; 6(8): 26- 34. Page 27 Kanchipuram District, Chennai with an ACS between January 2018 to May 2019 were eligible for inclusion in the study if coronary angiography (±PCI) was planned and they were adequately pretreated with Ticagrelor or clopidogrel and aspirin. An ACS was defined as symptoms suggestive of myocardial ischemia lasting > 15 min with either troponin elevation or new electrocardiogram (ECG) changes consistent with myocardial ischemia. ECG changes consistent with myocardial ischemia included ≥ 1 mm of ST-segment deviation or T wave inversion ≥ 1 mm in at least 2 contiguous leads. Troponin was considered elevated if greater than 14 ng/L, with a rise and/or fall of 50% if 14-50 ng/L or 20% if >50 ng/L in a subsequent measure. Results: The mean age was 63 ± 12 years with 71.9% being male and 18% having diabetes. Patients predominantly presented with NSTEMI 76% and 24% as STEMI. Patients treated with Ticagrelor were younger, more likely to be male, less likely to present with STEMI, have suffered a previous MI, experience atrial fibrillation and be taking proton pump inhibitors or calcium channel blockers. Patients who were administered Ticagrelor demonstrated significantly lower platelet reactivity when stimulated with ADP compared to patients administered clopidogrel (30.3 AU vs 43.7 AU respectively, p<0.0001). Conclusion: This study demonstrates that Ticagrelor provides more potent platelet inhibition than clopidogrel measured by MEA. This is reflected in ticagrelor’s ability to reduce the proportion of ACS patients experiencing HOTPR. Different clinical factors contribute to HOTPR in ACS patients treated with Ticagrelor or clopidogrel. Clopidogrel dose, renal insufficiency, clinical presentation, and platelet count are linked to clopidogrel HOTPR. In contrast, only a history of myocardial infarction is associated with Ticagrelor HOTPR.

Evaluation of platelet activity by multiple electrode impedance aggregometry in acute coronary syndromes: pilot study in a Brazilian tertiary-care public hospital

There is no definite recommendation for testing platelet aggregation (PA) in acute coronary syndromes (ACS) due to inconclusive evidence on the usefulness of platelet function tests to guide therapy and improve clinical outcomes. The evaluation of PA with multiple electrode impedance platelet aggregometry (MEA) may be useful to manage antiplatelet therapy and possibly influence patient outcome. The primary aim of this study was to measure PA with MEA in Brazilian patients with ACS and evaluate the association between PA and adverse clinical outcomes. Forty-seven consecutive patients admitted with ACS to a Brazilian tertiary-care public hospital were studied and PA was evaluated using MEA. Patients were followed for six months for the occurrence of all-cause death, acute myocardial infarction, or stroke. Suboptimal inhibition of PA was found in 7 patients (14.9%); 5 (10.6%) in response to ASA (acetylsalicylic acid), 2 (5.0%) to clopidogrel, and none to ticagrelor. Inadequate PA inhibition in response to ASA was significantly associated with the composite end point, but there was no significant association for insufficient PA inhibition in response to clopidogrel. This study suggested that the evaluation of PA in ACS using MEA may identify non-responders to ASA. Larger studies are necessary to define, in a public health scenario, the value of MEA in the management of ACS.

Damage of dual antiplatelet drug to gastrointestinal mucosa and endoscopic diagnosis and treatment / 中国实用内科杂志

Antiplatelet drugs are widely used in primary and secondary prevention of vascular embolism diseases, which can reduce the occurrence of cardiovascular and cerebrovascular adverse events. However, while inhibiting platelet aggregation, dual antiplatelet drugs can also affect the repair of gastrointestinal mucosa, leading to gastric ulcer formation and bleeding. More severely, patients may die from hemorrhage. The risk of severe hemorrhage increases significantly following a combination antiplatelet drug regimen. Endoscopic hemostasis should be the first choice for patients with gastrointestinal hemorrhage caused by dual antiplatelet therapy. Benefits and risks should be balanced. In order to prevent gastrointestinal mucosal injury caused by dual antiplatelet therapy, standardized process should be adopted to assess and screen the risk of patients, and the indications of antiplatelet therapy should also be standardized. Meanwhile,high-risk population of gastrointestinal injury should be identified in advance. In order to minimize the occurrence of gastrointestinal injury and bleeding, appropriate protective measures should be taken.

Ticagrelor plus aspirin versus clopidogrel plus aspirin on graft patency after coronary artery bypass graft surgery: A randomized controlled trial / 中国胸心血管外科临床杂志

@#Objective    To compare the effect of aspirin+ticagrelor and aspirin+clopidogrel on graft patency one year after coronary artery bypass grafting (CABG). Methods    A total of 67 patients who received CABG in our department from January 2014 to September 2017 were included in this study (52 males and 15 females). They were randomly divided into a group A (aspirin+clopidogrel) and a group B (aspirin+ticagrelor). There were 34 participants in the group A (28 males and 6 females) and 33 patients in the group B (24 males and 9 females). All patients were invited for clinical follow-up and 64-slice multislice computed tomography angiography (MSCTA) analysis in 1 year postoperatively. Cardiovascular events, bleeding events and other adverse events were followed up. Results    Four patients were lost to follow-up. Two patients died. A total of 61 patients (48 males and 13 females) completed coronary CTA, and 31 in the group A (25 males and 6 females) and 30 in the group B (23 males and 7 females). The total number of bridged vessels was 156 (59 internal thoracic artery bridges and 97 great saphenous vein bridges), including 79 in the group A (31 internal thoracic artery bridges and 48 great saphenous vein bridges) and 77 in the group B (28 internal thoracic artery bridges and 49 great saphenous vein bridges). Graft patency rate 1 year post CABG was 82.3% (65/79) in the group A and 92.2%(71/77) in the group B (P>0.05). Artery graft patency rate 1 year post CABG was 96.8% (30/31) in the group A and 96.4%(27/28) in the group B (P>0.05). Saphenous vein graft patency rate 1 year post CABG was 72.9% (35/48) in the group A  and 89.8% (44/49) in the group B (P<0.05). Multivariable analysis with binary logistic regression showed ticagrelor use reduced graft occlusion (OR=0.282, 95%CI 0.093 to 0.862, P<0.05). There was no significant difference in adverse events between the two groups. Conclusion    Compared with clopidogrel plus aspirin, ticagrelor added to aspirin after CABG may enhance the saphenous graft patency without the excess risk of bleeding 1 year post CABG.

The Evolving Concept of Dual Antiplatelet Therapy after Percutaneous Coronary Intervention: Focus on Unique Feature of East Asian and “Asian Paradox”

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is essential after percutaneous coronary intervention (PCI), while many studies have focused on determining the optimal degree of platelet inhibition and optimal DAPT duration to minimize complications after PCI. Current guidelines developed by the American College of Cardiology/American Heart Association and the European Society of Cardiology summarize previous studies and provide recommendations. However, these guidelines are mainly based on Western patients, and their characteristics might differ from those of East Asian patients. Previous data suggested that East Asian patients have unique features with regard to the response to antiplatelet agents. On comparing Western and East Asian patients, it was found that East Asian patients have a lower rate of ischemic events and higher rate of bleeding events after PCI, despite a higher on-treatment platelet reactivity, which is referred to as the “East Asian paradox.” As the main purpose of DAPT is to minimize ischemic and bleeding complications after PCI, these differences should be clarified before adopting the guidelines for East Asian patients. Therefore, in this article, we will review various issues regarding DAPT in East Asian patients, with a focus on the unique characteristics of East Asian patients, previous studies regarding antiplatelet agents in East Asian patients, and a guideline from an East Asian perspective.

Predictive value of the GRACE discharge score on the long-term out-of-hospital coronary thrombotic events after implantation of drug-eluting stents / 中华心血管病杂志

Objective@#To evaluate the predictive value of GRACE discharge score on the long-term out-of-hospital coronary thrombotic events (CTE) after percutaneous coronary intervention (PCI) with drug-eluting stents.@*Methods@#Present study was a prospective, observational, single center study. 10 724 consecutive patients underwent PCI in Fuwai Hospital between January and December 2013 were included, stents were implanted with conventional method. After PCI, patients were prescribed aspirin 100 mg once daily indefinitely, and either clopidogrel 75 mg once daily or ticagrelor 90 mg twice daily for at least 1 year. A total of 9 782 patients were included in the final analysis after excluding patients who did not undergo successful stent implantation, who were not discharged on dual anti-platelet therapy (DAPT), who only underwent bare-metal stents, who experienced in-hospital major bleeding, stent thrombosis, myocardial infarction (MI) or death,and who lost follow up. Clinical data were collected from all patients. 9 543 patients with complete baseline data were further analyzed for risk stratification and predictive value of GRACE discharge score. CTE was defined as stent thrombosis or spontaneous myocardial infarction. All patients were followed through Fuwai Hospital Follow-up Center, and evaluated either by phone, letter, or clinic visits or at 1, 6, 12 and 24 months after PCI. Risk stratification was performed according to the GRACE discharge score, and the predictive value of the GRACE discharge score was assessed using the receiver operating characteristic (ROC) curve.@*Results@#After 2 years follow-up, there were 95 CTE among the 9 782 patients. The patients were divided into 2 groups according to the presence or absence of CTE: CTE group (95 cases) and no CTE group (9 687 cases). GRACE discharge score was significantly higher in CTE group than no CTE group (82.98±27.58 vs. 75.51±22.46, t=-2.57, P=0.012). According to risk stratification of GRACE discharge score, the patients were divided into low-risk (≤88) group (n=6 902), moderate-risk (89-118) (n=2 988) and high-risk (>118) (n=343) groups. As compared to the low-risk group, CTE risk in moderate- and high-risk groups was 1.59 times (HR 1.59, 95%CI 1.01-2.52, P=0.046) and 3.89 times higher (HR 3.89, 95%CI 1.98-7.65, P<0.001), respectively. Further analysis showed that the GRACE score had predictive value in the total cohort for CTE (area under the receiver operating characteristic (AUROC) 0.576, 95%CI 0.512-0.640, P=0.012) and in the acute coronary syndromes(ACS) subgroup for CTE: (AUROC 0.594, 95%CI 0.509-0.680, P=0.019), but not in the non-ACS subgroup: (AUROC 0.561, 95%CI 0.466-0.657, P=0.187).@*Conclusion@#GRACE discharge score can predict the long-term out-of-hospital CTE in patients undergoing PCI with drug-eluting stents and treated with DAPT, and patients can be stratified into the low-, moderate- and high-risk groups of CTE by the GRACE discharge score.

Six versus twelve months of dual antiplatelet therapy after implantation of biodegradable polymer sirolimus-eluting stent in elderly patients / 中国介入心脏病学杂志

Objective To explore the eff cacy and safety of 6-month and 12-month dual antiplatelet therapy(DAPT)after implantation of biodegradable polymer-drug eluting stents(BP-DES) in elderly patients. Methods This study was a subgroup analysis of the I-LOVE-IT 2 trial, which was a prospectively randomized study enrolling 2737 patients receiving either a BP-SES or a DP-SES in a 2:1 ratio. This studied further divided the patients who were randomized to the BP-SES group,whose age ≥ 65 year old, in a 1:1 ratio to receive a 6-month DAPT (n=319) or 12-month DAPT (n=308)randomly before the index PCI. The primary end point of this study was 12-month target lesion failure (FhF, including cardiac death,target vessel myocardial infarction and clinically indicated target lesion revascularization)and the secondary end points was 12-month net adverse clinical and cerebral events (including all-cause death, all myocardial infarction, stroke and all bleeding). Results Rates of TLF at 12 months were 7.1% in the 6-month DAPT group and 7.2% in the 12-month DAPT group (P=0.980). No diff erences were observed in the occurrence of events in the secondary endpoint at 12 months follow-up between the 6-month DAPT group and 12-months DAPT group(14.1% versus 13.0%, P=0.726). There were no signifi cant diff erences in stent thrombosis or bleeding complications between the 2 groups. Conclusions This study shorted that 6-month DAPT did not increase the risk of TLF at 12 months after implantation of DES in elderly patients compared with 12-month DAPT. Elderly patients are at high risk of bleeding and ischemic events and study show that 6-month DAPT would be adequate. These results need to be confi rmed with trials of scale in the future.

Effects of preoperative continued dual antiplatelet therapy on early outcomes in patients undergoing off-pump coronary artery bypass grafting / 天津医药

Objective To evaluate the effects of preoperative continued dual antiplatelet therapy (DAPT) with aspirin and clopidogrel on early outcomes in patients underwent off-pump coronary artery bypass grafting (OPCABG). Methods A single-center study was conducted. The 279 unstable angina patients underwent first-time isolated OPCABG at our institution from January 2015 to May 2016 were divided into DAPT group (preoperative aspirin 100 mg/d and clopidogrel 75 mg/d were given until the time of surgery, n=148) and control group (stopped DAPT for 5 days before surgery, n=131). The total chest-tube output, blood-product transfusion requirements, re-exploration rate for bleeding, major adverse cardiac events (MACE) and other in-hospital outcomes were collected and compared between the two groups. Results There were no significant differences in demographic and preoperative clinical characteristics between the two groups. The total chest-tube drainage volume and perioperative transfusion requirements (rate and volume) including red blood cell, fresh plasma and platelets were statistically higher in the continued DAPT group than those of control group (P < 0.05). There were no significant differences in hemostatic re-exploration rate, length of operation, postoperative nonfatal myocardial infarction, ICU stay, ventilation time and duration of postoperative hospitalization between the two groups. Stroke and other severe outside chest bleeding and all-cause mortality were not observed in both groups during the postoperative period and prior to discharge. Conclusion Preoperative continued DAPT is associated with the increased chest-tube drainage and higher blood-product transfusion requirements but it does not increase the dection rate of thoracotomy because of bleeding. This antiplatelet strategy does not alter other investigated outcomes in primary isolated OPCABG patients. The preoperative DAPT may be able to be safely continued in patients referred for primary isolated OPCABG.

Association of α2A-Adrenergic Receptor Genetic Variants with Platelet Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in individuals modifies the antiplatelet response to sympathetic stimulation. The aim of this study was to investigate the effect of ADRA2A variants on platelet reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after undergoing percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From March 2011 to March 2013, 1,024 patients were enrolled in this prospective, single-center, observational study in China. Four single nucleotide polymorphisms (SNPs) of ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP) inhibition was detected by thromboelastography (TEG®).</p><p><b>RESULTS</b>The minor allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was significantly different among patients carrying rs11195419 (adjusted P = 0.022) and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest ADP inhibition. However, ADP inhibition was not significantly different in rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033), rs3750625 (P = 0.020) and CYP2C19*2 (P = 0.002) were independent predictors of ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males, but not in females.</p><p><b>CONCLUSION</b>ADRA2A genetic variations were associated with ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI, and the effect was particularly more pronounced in males.</p>