Clopidogrel In Chinese Patients Research Articles

Effects of ticagrelor monotherapy vs. clopidogrel monotherapy on platelet reactivity: a randomized, crossover clinical study (SINGLE study)

Increasing clinical trials demonstrated that the discontinuation of aspirin while maintaining a P2Y12 inhibitor monotherapy could decrease the risk of bleeding without losing the antithrombotic effect. However, no data are available on the platelet reactivity of patients undergoing ticagrelor monotherapy vs. clopidogrel. Therefore, we performed this study to observe the efficacy of ticagrelor monotherapy vs. clopidogrel in Chinese patients with chronic coronary syndrome. This randomized, single-blinded, crossover trial enrolled 50 patients who were administered with ticagrelor (90 mg twice daily for 2 weeks) or clopidogrel (75 mg once daily for 2 weeks). Followed by a 2-week washout period, the two groups of patients underwent a crossover trial. Light transmission aggregometry (LTA) and thromboelastography (TEG) assays were used to test platelet reactivity. The platelet aggregation rate (PAgR) of ADP and AA was significantly lower with ticagrelor than clopidogrel (PAgR of ADP, 27.30% (7.30%-42.635%) vs. 35.55% (12.03%-69.25%), P = .0254; PAgR of AA, 77.80% (21.60%-86.43%) vs. 83.10% (67.13%-87.20%), P = .0400). There was no significant difference in PAgR of collagen and epinephrine between the two groups. The TEG assay showed that ADP and AA, which induced the inhibition of platelet aggregation, were significantly higher in the ticagrelor group than those in the clopidogrel group [ADP%, 69.00% (59.68%–88.95%) vs. 60.55% (35.98%–78.35%), P = .0020; AA%, 53.65% (22.75%–79.28%) vs. 15.15% (5.75%–70.25%), P = .0127]. High on-treatment platelet reactivity (HTPR) on ADP was 2.17% with ticagrelor and 19.57% with clopidogrel. HTPR on AA was 50.00% with ticagrelor and 69.57% with clopidogrel. Ticagrelor and clopidogrel caused the inhibition of ADP and AA-induced platelet aggregation. Moreover, ticagrelor monotherapy had a stronger inhibitory effect than clopidogrel monotherapy (except on collagen and epinephrine).

Safety and Efficacy Evaluation of Antithrombotic Therapy with Rivaroxaban and Clopidogrel After PCI in Chinese Patients.

ObjectiveTo investigate the efficacy and safety of the antithrombotic therapy using the oral anticoagulant rivaroxaban and clopidogrel in Chinese patients with acute coronary syndrome complicated with atrial fibrillation after percutaneous coronary intervention.MethodsA total of 100 patients were selected. Patients were randomly divided into two groups: the treatment group (rivaroxaban group) received a therapy of rivaroxaban and clopidogrel. The control group (warfarin group) receivied a combined treatment of warfarin, clopidogrel, and aspirin. The primary outcome endpoint was evaluated based on the adverse cardiac and cerebrovascular events within 12 months.ResultsA total of 8 (8.00%) main adverse cardiac and cerebrovascular events occurred during the 12 months of follow-up, including 5 (9.80%) in the warfarin group and 3 (6.10%) in the rivaroxaban group. The risk of having main adverse cardiac and cerebrovascular events in the two groups was comparable (P = 0.479). A total of 9 patients (9.00%) were found to have bleeding events, among which 8 patients (15.7%) were in the warfarin group, whereas only 1 patient (2.00%) was in the rivaroxaban group. Therefore, the risk of bleeding in the warfarin group was significantly higher than that in the rivaroxaban group (P = 0.047).ConclusionsIn Chinese patients with acute coronary syndrome complicated with atrial fibrillation, the efficacy of the dual therapy of oral anticoagulant rivaroxaban plus clopidogrel after percutaneous coronary intervention was similar to that of the traditional triple therapy combined with warfarin, aspirin and clopidogrel, but it has a better safety property, which has potential to widely apply to antithrombotic therapy after PCI

Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein Ⅱb/Ⅲa receptor antagonist

Objective: To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI). Methods: The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization. Results: A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI (OR=0.881, 95%CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group (OR=1.401, 95%CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group (OR=0.919, 95%CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group (OR=1.559, 95%CI 1.130-2.150; P=0.007). Conclusion: In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

An Observational Study of the Relationship Between Outcome and Platelet Reactivity in Chinese Patients Undergoing PCI Loading with 600 mg Clopidogrel

Objectives: We sought to determine whether high posttreatment platelet reactivity (HPPR) to a 600 mg loading dose of clopidogrel affects outcomes in Chinese patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) and to investigate whether there is a relationship between the number of platelet reactivity units (PRUs) and the characteristics of the patients. Background: Although impaired platelet response to clopidogrel is a strong predictor of unfavorable outcome after PCI, the impact of HPPR to a 600 mg loading dose of clopidogrel in Chinese patients with ACS undergoing PCI is still unknown. Methods: We performed observational research on 134 unselected patients with ACS undergoing urgent or planned PCI with a 600 mg loading dose of clopidogrel. Platelet activation was expressed as the PRU value measured by the VerifyNow assay. Results: Among the 134 patients (mean age 60.62 years [standard deviation 9.13 years], 60.4% male), there were 46 patients with HPPR (34.3%) and 88 patients without HPPR (65.7%). At a mean follow-up of 6 months (standard deviation 1 month), the rates of cardiac death, unstable angina, and rehospitalization for target lesion revascularization were higher in the HPPR group (19.6% vs. 6.8%, P=0.029). Multivariate analysis identified hemoglobin level and sex as independent predictors of the PRU value (y=456.355−1.736x 1−31.880x 2, P<0.05). On receiver operating characteristic curve analysis, PRU values could significantly discriminate between patients with and patients without cardiac death, unstable angina, and rehospitalization for target lesion revascularization (area under the curve 0.758, 95% confidence interval 0.62–0.85, P=0.001, P<0.05). Conclusion: In patients with ACS, HPPR to a 600 mg loading dose of clopidogrel is associated with worse outcomes after PCI. There is some relationship between the PRU value and the hemoglobin level and sex. PRU values can predict the prognosis.

Comparison of Antiplatelet Effects and Clinical Outcomes Between Ticagrelor Versus Clopidogrel in Chinese Patients With Acute Coronary Syndrome.

Comparison of Antiplatelet Effects and Clinical Outcomes Between Ticagrelor Versus Clopidogrel in Chinese Patients With Acute Coronary Syndrome.

A14513 The impact of cigarette smoking on platelet response to clopidogrel in Chinese patients undergoing percutaneous coronary intervention

Objectives: Clopidogrel, is widely used in patients undergoing percutaneous coronary intervention (PCI). As an inducer of CYP1A2, cigarette smoking may theoretically enhance the clinical efficacy of clopidogrel. The purpose of this study was to investigate effects of cigarette smoking habits on the platelet response to clopidogrel. Methods: A total of 713 patients undergoing PCI were enrolled from Beijing Shijingshan Hospital and assigned to the treatment with a daily dose of 75 mg of clopidogrel. The patients’ smoking habits were obtained from questionnaire surveys. ADP-induced platelet inhibition was measured by thrombelastography (TEG). Results: For current smokers, significant higher ADP-induced platelet inhibition rate was found compared with nonsmokers and previous smokers (75.92 ± 22.76% vs. 65.55 ± 23.85% vs. 69.16 ± 26.57%, P = 0.019). After dividing patients (excluding previous smokers) into three groups by daily cigarettes (0, < 20, > = 20 cigarettes/day), the incidence of high on-treatment platelet inhibition (HTPI) increased and the trend was significant (P < 0.0001). Similarly, after grouping patients (excluding previous smokers) according to the years of smoking (0, < 30, > = 30 years), with increase of the smoking years, the occurrence of HTPI became higher (P < 0.0001).In a multivariate logistic regression analysis, cigarette smoking was an independent influencing factor for HTPI (OR [95% CI] = 1.497 [1.114–2.013], P = 0.007). Conclusion: Current smoking could enhance ADP-induced platelet inhibition during clopidogrel therapy in Chinese patients undergoing PCI. The study also demonstrated that smoking intensity may affect the response to clopidogrel.

Impact of Baseline Bleeding Risk on Efficacy and Safety of Ticagrelor versus Clopidogrel in Chinese Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Background:There was still conflict on the antithrombotic advantage of ticagrelor versus clopidogrel among East Asian population with acute coronary syndrome (ACS). We considered that the baseline bleeding risk might be an undetected key factor that significantly affected the efficacy of ticagrelor.Methods:A total of 20,816 serial patients who underwent percutaneous coronary intervention (PCI) from October 2011 to August 2014 in the General Hospital of Shenyang Military Region were enrolled in the present study. Patients receiving ticagrelor or clopidogrel were further subdivided according to basic bleeding risk. The primary outcome was net adverse clinical events (NACEs) defined as major adverse cardiac or cerebral events (MACCE, including all-cause death, myocardial infarction, ischemia-driven target vessel revascularization, or stroke) and any bleeding during 1-year follow-up. Comparison between ticagrelor and clopidogrel was adjusted by propensity score matching (PSM).Results:Among the 20,816 eligible PCI patients who were included in this study, there were 1578 and 779 patients in the clopidogrel and ticagrelor groups, respectively, after PSM, their clinical parameters were well matched. Patients receiving ticagrelor showed comparable NACE risk compared with those treated by clopidogrel (5.3% vs. 5.1%, P = 0.842). Furthermore, ticagrelor might reduce the MACCE risk in patients with low bleeding risk but increase MACCE in patients with moderate-to-high bleeding potential (ticagrelor vs. clopidogrel, low bleeding risk: 2.5% vs. 4.9%, P = 0.022; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.225; interaction P = 0.021), with vast differences in all bleeding (low bleeding risk: 1.5% vs. 0.8%, P = 0.210; moderate-to-high bleeding risk: 4.8% vs. 3.0%, P = 0.002; interaction P = 0.296).Conclusion:Among real-world Chinese patients with ACS treated by PCI, ticagrelor only showed superior efficacy in patients with low bleeding risk but lost its advantage in patients with moderate-to-high bleeding potential.

OS 34-05 HIGH ON-TREATMENT PLATELET REACTIVITY WAS ASSOCIATED WITH SMOKING IN CLOPIDOGREL-TREATED PATIENTS

Objective: High on-treatment platelet reactivity (HTPR) was associated with an increased risk of ischemic events in clopidogrel-treated patients. Cigarette smoking was considered as an inducer of CYP1A2, and may theoretically enhance the biological effects and clinical efficacy of clopidogrel through facilitating the conversion of clopidogrel into its active metabolite. The purpose of this study was to examine the effect of cigarette smoking on the platelet response to clopidogrel. Design and Method: A total of 713 patients undergoing percutaneous coronary intervention were selected from Beijing Shijingshan Hospital and assigned to treatment with a loading 300 mg dose of clopidogrel. All patients are Han ethnicity from local community in Beijing. ADP-induced platelet aggregation inhibition was measured by thrombelastography (TEG). Results: For both previous smokers and nonsmokers, significantly lower ADP-induced platelet aggregation inhibition were found compared with current smokers (69.16 ± 26.57 vs. 75.92 ± 22.76, p = 0.017 and 65.55 ± 23.85 vs. 75.92 ± 22.76, p = 0.006, respectively). Yet, previous smokers had higher ADP-induced platelet inhibition than nonsmokers, but the difference was not significant (p = 0.996). During clopidogrel therapy, ADP-induced platelet aggregation inhibition trended higher in current smokers whose length of smoking was more than or equal to 25 years than whose length of smoking was less than 25 (p = 0.045). Similarly, current smokers of 11–20 and > 20 cigarettes per day displayed greater platelet inhibition compared with nonsmokers (75.68 ± 23.30 vs. 65.55 ± 23.85, p = 0.027 and 77.22 ± 22.23 vs. 65.55 ± 23.85, p = 0.035, respectively). In a multivariate logistics regression analysis, cigarette smoking was an independent influencing variable for high on-treatment platelet inhibition (OR = 1.550, p = 0.004). Conclusions: In our study, cigarette smoking was positively associated with enhanced response to clopidogrel. The study also demonstrated that the length of smoking and amount of cigarettes smoked appeared to affect the response to clopidogrel in Chinese patients undergoing percutaneous coronary intervention.

Abstract 339: Comparison of the Antiplatelet Effect Between Ticagrelor and Clopidogrel in Chinese Patients with Acute Myocardial Infarction After Primary Percutaneous Coronary Intervention

Background: Ticagrelor can provide effective platelet inhibition 2 hours after a loading dose, but it will take 6 hours for clopidogrel. It is not very clear whether the anthplatelet agents treated patients with AMI undergoing primary PCI can achieve ideal antiplatelet effect after 24 to 48 hours. Purpose: The aim is to compare the antiplatelet action between ticagrelor and clopidogrel in Chinese patients with AMI after primary PCI. Methods: 189 patients with AMI after primary PCI were enrolled in this single center registry. All patients received loading and maintenance dose of dual antiplatelet therapy (aspirin+clopidogrel/ticagrelor). 58 cases were included in ticagrelor group. 131 patients were included in clopidogrel group. Residual platelet reactivity was assessed by VerifyNow 24-48 hours after PCI. All patients were followed-up for 30 days and 6 months after discharge. Results: The baseline data were well matched between the two groups. After 24-48 hours, 51 cases existed of high residual platelet response(HRPR)(platelet response unit ,PRU≥230), the ratio was 26.98%. In clopidogrel group, the average PRU was 195.8 (26~329), and 43 patients existed HRPR, ratio was 32.82%. For ticagrelor group, the average PRU was 101.8 (6~322), and 8 patients existed HRPR, ratio was 14.04%. The incidence of HRPR was significantly lower in ticagrelor group ( p &lt; 0.0001). Within 30 days, the incidence of MI in clopidogrel group and ticagrelor group were respectively 0.8% and 0, p =0.693; target lesion revascularization were 1.7% and 1.5%, p =0.669; death were 0.8% and 0, p =0.693; stroke were 0 and 0, p =1.000; bleeding were 2.3% and 0, p =0.331. In 6 months, the incidence of MI were 0.8% and 0, p =0.693; target lesion revascularization were 0.8% and 0, p =0.693; death were 0 and 0, p =1.000. The incidence of MACE, bleeding and stroke had no obvious difference between the two groups. Conclusion: 24 hours after primary PCI, there are still a large proportion of Chinese patients with AMI existing insufficient platelet inhibition, no matter they take clopidogrel or ticagrelor, but ticagrelor has a significant stronger antiplatelet effect than clopidogrel. There is no obvious difference between the incidences of clinical events.

One-quarter standard-dose ticagrelor better than standard-dose clopidogrel in Chinese patients with stable coronary artery disease: A randomized, single-blind, crossover clinical study

BackgroundTicagrelor has been demonstrated to provide a more rapid and powerful inhibition of platelet aggregation compared with clopidogrel in coronary artery disease (CAD) patients. In our previous study, we found that half-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose ticagrelor and exerted significantly stronger effects than clopidogrel in Chinese patients with non-ST-elevation ACS. Therefore, we performed this study to observe the efficacy of one-quarter standard-dose ticagrelor in comparison to standard-dose clopidogrel in Chinese patients with stable CAD. MethodsIn a randomized, single-blind, crossover trial, 30 patients with stable CAD were randomized to one-quarter standard-dose ticagrelor (22.5mg BID for 7days) or standard-dose clopidogrel (75mg QD for 7days). Following a 2-week washout period, patients switched regimens. Light transmission aggregometry (LTA) and VerifyNow assay were used to measure platelet function. ResultsThe platelet aggregation rate (PAgR) was obviously lower with ticagrelor than clopidogrel (17.70%±12.67% versus 27.63%±13.10%, P<0.05). The % inhibition levels in the ticagrelor group exhibited significantly greater than that in the clopidogrel group (65.33%±21.31% versus 36.23%±23.01%, P<0.01). PRU values in the ticagrelor group were dramatically lower than that in the clopidogrel group (87.03±51.38 versus 163.77±58.66, P<0.01). High-platelet reactivity (HPR) (≥208 PRU) was 0% with ticagrelor and 16.67% with clopidogrel. ConclusionsOne-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard-dose clopidogrel in Chinese patients with stable CAD.

Ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome: A pharmacodynamic analysis

Ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome: A pharmacodynamic analysis

Influence of genetic and non-genetic factors on the plasma concentrations of the clopidogrel metabolite (SR26334) among Chinese patients

The objective of this study was to investigate the contribution of genetic polymorphism of cytochrome P450 2C19 gene (CYP2C19) and non-genetic factors to clopidogrel in Chinese patients by using the plasma concentrations of SR26334 as a surrogate. A total of 150 patients who received clopidogrel therapy were enrolled in this study. Genotyping was carried out to identify the alleles of CYP2C19*2 and CYP2C19*3 by using PCR-based restriction enzyme tests. The plasma concentrations of SR26334 were determined using a rapid LC method with UV detection. CYP2C19 genotyping showed that 68 patients were extensive metabolizers (EMs), 68 were intermediate metabolizers (IMs) and 14 were poor metabolizers (PMs). Multiple linear regression models incorporating genetic polymorphism of CYP2C19 and non-genetic factors, such as blood collection time, smoking status and clopidogrel doses were developed, and explained up to 63.1% of the total variation (adjusted R2 of 0.631) in the plasma concentrations of SR26334 in Chinese patients. Blood collection time, smoking status, genetic polymorphism of CYP2C19 and clopidogrel doses were found to affect the plasma concentrations of SR26334 significantly.

Effect of proton pump inhibitors on platelet inhibition activity of clopidogrel in Chinese patients with percutaneous coronary intervention

Background:The purpose of this study was to examine the effect of proton pump inhibitors (PPI) on the antiplatelet activity of clopidogrel in a consecutive series of Chinese patients after they had received coronary stents.Methods:A sample of 51 consecutive Chinese patients treated with coronary stents and taking PPI and clopidogrel for more than 30 days were enrolled in this study. Mean values for platelet residual units and percentage inhibition before PPI (+PPI) and 14 days after discontinuation of PPI (−PPI) were compared using the paired t-test.Results:There was no effect of concomitant use of esomeprazole and clopidogrel or omeprazole and clopidogrel on the inhibition assay, but platelet residual units and percentage inhibition showed statistically significant improvement after stopping lansoprazole in Chinese patients who were on chronic clopidogrel therapy. Clopidogrel resistance existed more frequently in the Chinese-American population examined, and was as high as 68% (+PPI) to 73% (−PPI).Conclusion:The clopidogrel resistance found is cause for concern, although its relationship with clinical events is currently unknown in this population. Further study with other thienopyridines or genetic variant analysis is suggested.

E0458 Comparative study of aspirin and clopidogrel in high risk ACS

BackgroundIt is not reasonable to administrate the same dosage of antiplatelet medicine to all patients with ACS regardless of patients’ height, weight, metabolism and effectiveness of those medicines. And thromboelastography...