Background: Antiplatelet resistance is one factor that contributes to stroke recurrence among patients with noncardioembolic ischemic strokes. Objectives: This paper aims to describe the prevalence of aspirin and clopidogrel resistance, along with frequency of statin, NSAID and proton pump inhibitor use among our cohort of stroke patients. Method. This is a single-center cross-sectional review that included all adult patients with recurrent noncardioembolic ischemic stroke admitted in a tertiary hospital between January 2019 and June 2023. Results: A total of 1,374 patients were admitted for ischemic stroke from January 2019 to June 2023. Among these, 155 (11.28%) were recurrent noncardioembolic ischemic strokes. Prevalence of aspirin and clopidogrel resistance were 25% and 32.7%, respectively. Clinical profiles of those in the resistant group were comparable with those in the nonresistant group. None of the patients taking aspirin had concomitant use of nonsteroidal antiinflammatory drugs. Only 2 of the patients who were resistant to clopidogrel were on proton pump inhibitors. More than half of the patients both in the resistant and the nonresistant groups were on statin. The study had a small sample size and hence it was not enough to establish causal relationship between factors and antiplatelet resistance. Conclusion More patients were resistant to clopidogrel than to aspirin. Further studies with a bigger sample size are recommended to explore factors that contribute to antiplatelet resistance in Filipino patients.
Aspirin ; Clopidogrel ; Ischemic Stroke ; Tertiary Care Centers

This article reviews the available published data on optimizing clopidogrel and aspirin therapy using translational and integrative medicine. Translational and evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation is closely associated with clopidogrel resistance and an increased risk of major adverse cardiovascular events, particularly stent thrombosis in patients following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is substantially more efficacious than aspirin. However, a poor compliance is a big problem in warfarin use especially in China. The genetic variants of vitamin K expoxide reductase might account for the universally lower warfarin dosage used in Chinese population. The available evidence indicates that the integrating mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19 gene mutation patients following PCI can be effective. Aspirin combined NXT and the adjusted-dose warfarin was equally effective in elderly patients with non-valvular AF in prevention of ischemic stroke.
Aspirin ; therapeutic use ; Clopidogrel ; therapeutic use ; Humans ; Integrative Medicine ; Translational Medical Research

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.
Aged ; Aged, 80 and over ; Female ; Humans ; Atherosclerosis ; Cardiovascular Diseases ; Cholesterol, LDL ; Clopidogrel/therapeutic use* ; Risk Factors

Clopidogrel is the cornerstone of antiplatelet therapy, but there are ethnic and individual differences in the suppression of platelets. Some patients regularly taking drugs still cannot prevent the recurrence of cardio- and cerebrovascular thrombosis, thereby manifest low drug reactivity, i.e., clopidogrel resistance. Genetic polymorphism is the main reason for individual difference. Genetic testing has been used for evaluating the efficacy of antiplatelet therapy, adjusting therapeutic plan, and predicting the risk of cardio- and cerebrovascular thromboembolic events by determining the genetic polymorphisms related with antiplatelet drugs. This article provides a review for the status quo and countermeasure of clopidogrel resistance predicted by gene testing.
Blood Platelets ; Clopidogrel ; Drug Resistance ; Genetic Testing ; Humans ; Platelet Aggregation Inhibitors ; Ticlopidine

To explore differential expression of long non-coding RNA (lncRNA) in patients with coronary artery disease plus clopidogrel resistance.
 Methods: Patients underwent percutaneous coronary intervention (PCI) and treated with clopidogrel were recruited, and their clinical data and blood samples were collected. Patients were divided into a clopidogrel sensitive group and a clopidogrel resistance group according to platelet aggregation rate. lncRNA microarray and real-time RT-PCR were performed in 5 and 34 patients in each group, respectively.
 Results: lncRNA microarray showed that 11 lncRNAs in peripheral leukocytes were up-regulated and 8 lncRNAs were down-regulated in clopidogrel resistant group. Real-time PCR indicated that two lncRNAs (NONHSAT083775.2 and NONHSAT107804.2) in leukocytes were up-regulated and one lncRNA (NONHSAT133455.2) was down-regulated in the clopidogrel resistant group compared with the clopidogrel sensitive group, consistent with the results of lncRNA microarray.
 Conclusion: Clopidogrel resistance is associated with the up-regulation of lncRNA NONHSAT083775.2 and NONHSAT107804.2 and the down-regulation of NONHSAT133455.2.
Clopidogrel ; Coronary Artery Disease ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; RNA, Long Noncoding

OBJECTIVE: To study the clinical effect and safety of clopidogrel combined with aspirin in antithrombotic therapy for children with Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA). METHODS: A total of 77 KD children who were diagnosed with multiple small/medium-sized CAAs by echocardiography between January 2013 and June 2018 were enrolled. They were randomly divided into observation group with 38 children (treated with clopidogrel and aspirin) and control group with 39 children (treated with low-molecular-weight heparin and aspirin). All children were followed up regularly, and the first 3 months of the course of the disease was the observation period. The children were observed in terms of the change of the coronary artery and the incidence of complications. RESULTS: At month 3 of follow-up, among the children in the observation group, 6 had normal coronary artery, 11 had coronary artery retraction, 19 had stable coronary artery, and 2 progressed to giant coronary aneurysm; among the children in the control group, 7 had normal coronary artery, 12 had coronary artery retraction, 19 had stable coronary artery, and 1 progressed to giant coronary aneurysm; there was no significant difference in the change of the coronary artery between the two groups (P>0.05). There were 2 cases of epistaxis and 6 cases of skin ecchymosis in the observation group, and 1 case of epistaxis and 7 cases of petechiae and ecchymosis at the injection site in the control group, and no other serious bleeding events were observed in either group. CONCLUSIONS Clopidogrel combined with low-dose aspirin is safe and effective in antithrombotic therapy for children with KD complicated by CAA.
Aspirin ; therapeutic use ; Child ; Clopidogrel ; Coronary Aneurysm ; drug therapy ; etiology ; Coronary Vessels ; Fibrinolytic Agents ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications

Objective: To investigate the effects of clopidogrel resistence and CYP2C19 genotype on the clinical prognosis of acute coronary syndrome(ACS) patients undergoing percutaneous coronary intervention(PCI). Methods: This study was a retrospective cohort study. ACS patients who underwent PCI in Beijing Anzhen Hospital from October 2015 to January 2017 were recruited. The inhibition rate of adenosine diphosphate(ADP) was monitored by thromboelastography. All of these patients were divided into clopidogrel resistance and non-resistance group according to the monitoring results. CYP2C19 genotype was detected by TaqMan probe-based real-time quantitative PCR. Patients were divided into slow, medium and fast metabolic group, according to the CYP2C19 genotype. After 12 months of follow-up, the end points included all-cause death, cardiac death, angina, myocardial infarction, stent thrombosis, ischemic stroke and hemorrhage were collected. Combined thrombotic events were defined as a composite of angina, myocardial infarction, stent thrombosis and ischemic stroke. The differences of the incidence of clinical events between groups were compared. Cox regression was used to analyze the effects of clopidogrel resistance and CYP2C19 genotype on the combined thrombotic events, cardiac death and hemorrhage. Results: A total of 1 696 patients were included, and the age was (59.4±9.6) years, with 1 280(75.5%) males. There were 471 cases(27.8%) in clopidogrel resistance group, and 1 225 cases(72.2%) in clopidogrel non-resistance group. There were 218 patients(12.9%) were in slow metabolic group, 668(39.4%) in medium metabolic group, and 810 (47.8%) in fast metabolic group. The median follow-up time was 13.3 months, and 131 cases were lost to follow-up, with a loss follow-up rate of 7.7%. Compared with the clopidogrel non-resistance group, the clopidogrel resistance group had a higher incidence of myocardial infarction(7.6%(36/471) vs. 5.1%(62/1 225), P=0.041), a lower incidence of hemorrhage (13.2%(62/471) vs. 17.9%(219/1 225), P=0.020) and minor hemorrhage(11.5%(54/471) vs. 15.8% (194/1 225), P=0.022). There were no statistically significant difference in all-cause death, cardiac death, angina, stent thrombosis, ischemic stroke and severe bleeding between clopidogrel resistance and non-resistance group(all P>0.05). There was no statistically significant difference in the incidence of endpoint events among different CYP2C19 genotypes (all P>0.05). Cox regression analysis showed that clopidogrel resistance was an independent factor of combined thrombotic events (OR=2.334, 95%CI 1.215-4.443, P=0.016) and bleeding events (OR=0.481, 95%CI 0.174-0.901, P=0.023). While CYP2C19 genotype was not independent factor for combined thrombotic events, cardiac death and hemorrhage (all P>0.05). Conclusion: For ACS patients after PCI, clopidogrel resistance can increase the risk of combined thrombotic events, but also reduce the risk of bleeding; while CYP2C19 genotype is not an independent factor for clinical prognosis.
Acute Coronary Syndrome/genetics* ; Clopidogrel/therapeutic use* ; Cytochrome P-450 CYP2C19/genetics* ; Genotype ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Prognosis ; Retrospective Studies ; Treatment Outcome

Objective: To compare the efficacy and safety of ticagrelor and clopidogrel in elderly Chinese patients with acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI) in the real world. Methods: This study is a post-hoc analysis of a single center, retrospective cohort study. Between March 2016 and March 2018, elderly (age≥65) ACS patients who underwent PCI in the General Hospital of Northern Theater Command were included in the study. The patients were grouped according to P2Y₁₂ receptor inhibitor. The primary endpoints of this study were ischemic events during the 2-year follow-up, which were defined as the composite of cardiac death, myocardial or stroke. The secondary efficiency endpoints included all-cause death and BARC 2, 3, 5 bleeding events. Results: A total of 4 022 elderly (mean age: (71.5±5.3) years) ACS patients were included in this study. Based on the choice of P2Y₁₂ receptor inhibitor, patients were divided into clopidogrel (n=3 201) and ticagrelor (n=821) groups. Incidences of ischemic events (3.2% (26/821) vs. 5.6% (179/3 201), P=0.005) at 2 years were significantly lower in ticagrelor group compared to clopidogrel group. BARC 2, 3, 5 bleeding events (1.7% (14/821) vs. 1.6% (52/3 201), P=0.818) were comparable between the two groups. The incidence of all-cause death (1.5% (12/821) vs. 4.1% (132/3 201), P=0.005) were also lower in the ticagrelor group compared to the clopidogrel group. Clinical outcomes were consistent after adjusting for confounding factors, the incidence of ischemic events (HR= 0.637, 95%CI 0.409-0.991, P=0.046) and all-cause mortality (HR=0.402, 95%CI 0.213-0.758, P=0.005) was significantly lower in the ticagrelor group compared with the clopidogrel group. Risk of BARC 2, 3, 5 bleeding events were similar between the two groups (HR=0.957, 95%CI 0.496-1.848, P=0.897). Conclusion: In real-world clinical practice, for elderly patients with ACS undergoing PCI, ticagrelor use might reduce the incidence of long-term ischemic events and all-cause death without increasing the risk of bleeding.
Acute Coronary Syndrome/surgery* ; Aged ; Clopidogrel/therapeutic use* ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors/therapeutic use* ; Retrospective Studies ; Ticagrelor/therapeutic use* ; Treatment Outcome

Objective: To assess the prevalence, pattern and outcome of multimorbidity in elderly patients with acute coronary syndrome (ACS). Methods: Secondary analysis was performed based on the data from the BleeMACS registry, which was conducted between 2003 and 2014. We stratified elderly patients (≥65 years) according to their multimorbidity. Multimorbidity was defined as two or more chronic diseases in the same individual. Kaplan-Meier methods were used to estimate 1 year event rates for each endpoint, and comparisons between the study groups were performed using the log-rank test. The primary endpoint was net adverse clinical events (NACE), which is a composite of all-cause mortality, myocardial infarction, or bleeding. Results: Of 7 120 evaluable patients, 6 391 (89.8%) were with morbidity (1 594 with 1, 2 156 with 2, and 2 641 with ≥3 morbidity). Patients with morbidity were older, percent of female sex and non-ST-elevation acute coronary syndromes and implantation rate with drug-eluting stents and blood creatine level were higher compared to patients without morbidity. Compared with the patients without morbidity, the proportion of participants with oral anticoagulant increased in proportion to increased number of morbidities (5.8% vs. 6.4% with 1 morbidity, 7.3% with 2 morbidities, 9.0% with ≥3 morbidities, P trend<0.01) and the proportion of participants with clopidogrel prescription decreased in proportion to increased number of morbidity (91.9% vs. 89.7% with 1 morbidity, 87.9% with 2 morbidities, 88.6% with ≥3 morbidities, P trend = 0.01). During 1 year follow-up, compared with those with no morbidity, the hazard ratio (HR) and 95% confidence interval (CI) of risk of NACE for those with 1, 2, and ≥ 3 morbidities was 1.18 (0.86-1.64), 1.49 (1.10-2.02), and 2.74 (2.06-3.66), respectively (P < 0.01). Multimorbidity was not associated with an increased risk of bleeding of various organs (P>0.05). Conclusion: Multimorbidity is common in elderly patients with ACS. These patients might benefit from coordinated and integrated multimorbidity management by multidisciplinary teams.
Acute Coronary Syndrome/epidemiology* ; Aged ; Clopidogrel ; Female ; Hemorrhage ; Humans ; Multimorbidity ; Percutaneous Coronary Intervention/methods* ; Platelet Aggregation Inhibitors/adverse effects* ; Registries ; Treatment Outcome

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.
Aspirin/therapeutic use* ; Clopidogrel/therapeutic use* ; Coronary Artery Bypass/adverse effects* ; Drug Therapy, Combination ; Humans ; Isoindoles ; Male ; Phenylbutyrates ; Platelet Aggregation Inhibitors/therapeutic use* ; Prospective Studies ; Treatment Outcome