Mg Loading Dose Of Clopidogrel Research Articles

Platelet reactivity and activated clotting time predict haemorrhagic site complications in patients with chronic coronary syndromes undergoing percutaneous coronary intervention

Abstract Background/Introduction Same-day discharge has become a standard of care for patients with chronic coronary syndromes (CCS) treated with ad hoc percutaneous coronary interventions (PCI). QuickClot Radial kaolin-based haemostatic device may shorten haemostasis time and reduce the incidence of vascular site complications. Besides unfractionated heparin (UFH) and aspirin (ASA), an ad hoc procedure demands a loading dose of clopidogrel. Dynamic changes in platelets and thrombotic activity may influence the outcomes at vascular sites. Rapid "point-of-care" testing measures the effects of anticoagulation but the optimal threshold during and after PCI still requires further research. Purpose We investigated the effect of a standard dose of UFH and a loading dose of clopidogrel measured with point-of-care devices: Hemochron activated clotting time device (ACT), VerifyNow P2Y12 test on on-site outcomes. Methods We conducted a prospective, observational study of consecutive patients with CCS who qualified for ad hoc PCI. Patients were on chronic ASA therapy, received 100 IU/kg UFH, and a 600 mg loading dose of clopidogrel. ACT was measured before and 10 min, 2 h, and 6 h after the administration of UFH and clopidogrel, respectively, and the VerifyNow P2Y12 test measured after 2 and 6 h. A QuickClot haemostatic pad with gradually released compression for up to 2 h was used in all patients. Ultrasonographic assessment of artery diameter and patency was performed before and 6 h after the procedure. Bleeding (BARC criteria) or local haematoma (EASY scale) were observed regularly until hospital discharge. Results Forty patients were enrolled in the study. The mean±SD age was 68.8±8.8 years, 30 (75%) patients were men, 13 (35%) had diabetes, 38 (95%) hypertension, 16 (40%) previous myocardial infarction, and 15 (37,5%) were active smokers. Patients received a median [interquartile range (IQR)] 8000 [7000-9000] IU of UFH and 600 mg of clopidogrel. All of the radial arteries remained patent during observation; local bleeding (BARC 2) was observed in 11 (27,5%) and haematomas (EASY 1 and 2) in 11 (27,5%) patients. Patients with bleeding had lower platelet activity measured with platelet reactivity units (PRU) after 2 h (122.5± 51 vs 158.7± 43, p= 0.04) and higher ACT (s) (216.9 ±40 vs. 184.6±28 s, p=0.006). An ACT >196 s, measured 2 h after the procedure, predicted the occurrence of bleeding or haematoma (AUC 0.72; 95%CI 0.56-0.85, p=0.008). Conclusion Lower platelet activity and higher ACT after PCI were associated with higher risk of haemorrhagic site complications. "Point-of-care" measures post PCI in CCS patients may be clinically applicable.

Comparison Between the Incidence of Coronary No-Reflow in Patients with Acute ST-Elevation Myocardial Infarction receiving ticagrelor versus clopidogrel loading doses

Abstract Background Primary PCI is the preferred reperfusion strategy for ST segment elevation myocardial infarction (STEMI); because it offers prompt and complete recanalization of an occluded infarct-related artery. However, inspite of successfully restored (Thrombolysis in Myocardial Infarction [TIMI] grade 3) epicardial blood flow, myocardial reperfusion is not regained in some patients. This phenomenon is referred to as coronary no reflow. Such patients with no reflow have higher incidence of resting segmental wall motion abnormalities (SWMA), myocardial free wall rupture, and death. Objective To compare the effect of 180 mg ticagrelor versus 600 mg clopidogrel loading doses, on the incidence of no-reflow in acute ST segment elevation myocardial infarction (STEMI) patients. Material and Methods This study was carried out on 100 patients, presented with acute STEMI to Ain Shams university hospitals, in the period between November 2018 and February 2019 who underwent primary percutaneous coronary intervention (PCI). All patients were subjected to history, clinical examination, ECG recording before and after primary PCI, blood samples before primary PCI for (creatinine, CKTotal, CKMB in addition to routine laboratory investigations), and echocardiography after primary PCI. Patients were divided into two groups, where 50 patients received a 600 mg loading dose of clopidogrel and the other 50 received a 180 mg loading dose of ticagrelor prior to primary PCI. The primary endpoint was the occurrence of no reflow defined as TIMI flow grades ≤ 2 and or MBG of 0 or 1. The secondary endpoint was the occurrence of major adverse cardiac events during hospital stay. Results The primary endpoint of no reflow occurred in 17 (34%) patients in the clopidogrel group versus 12 (24%) patients in the ticagrelor group. This difference was not statistically significant (P-value 0.271). There was no significant statistical difference in the occurrence of major adverse cardiac events either. Conclusion The incidence of no reflow does not seem to be affected by the type of P2Y12 inhibitor loading received in the setting of STEMI. Further large-scale multi-center studies are required to prove or disprove the current evidence on the superiority of ticagrelor over clopidogrel in STEMI patients.

Epigenetic interaction of miRNA-26a and P2Y12 gene DNA methylation on platelet reactivity under clopidogrel and their impact to the coronary flow after primary PCI in STEMI

Abstract Background Epigenetic factors such as miRNA-26A and P2Y12 DNA methylation play role in pathophysiology of cardiovascular disease. Clopidogrel-resistance is associated with worse cardiovascular outcome. The interactions between the expression of platelet miRNA-26a and P2Y12 DNA methylation to clopidogrel resistance and post procedural TIMI flow in STEMI patients undergoing primary PCI is unclear. Purpose To define interaction of epigenetic factors micro-RNA (miRNA)-26a expression and P2Y12 gene DNA methylation to the platelet reactivity under clopidogrel therapy, and their impact on the coronary flow after Primary PCI in patients with STEMI. Methods We studied STEMI patients who underwent primary PCI, receiving 600 mg loading dose of clopidogrel. Platelet reactivity assessed by VerifyNow P2Y12. Realtime PCR was performed to measure the expression of platelet miR-26a and DNA methylation of P2Y12 gene. Postprocedural epicardial coronary flow was assessed semi quantitatively. Results There were 100 patients were recruited. Among them, 59% have high miRNA-26a platelet expression, 60% had no methylation in their P2Y12 gene, and 27% had high platelet reactivity index under clopidogrel therapy. There was association between high miR-26a expression and reduced platelet inhibition under clopidogrel (OR 4.2, p<0.01), but not with DNA methylation of P2Y12 gene. High platelet reactivity index under clopidogrel therapy was associated with suboptimal coronary flow after primary PCI in STEMI patients (OR 3.3, p<0.05). Conclusions High miRNA-26a platelet expression, but not DNA methylation of P2Y12 gene, in patients with acute STEMI have significant association with high platelet reactivity under clopidogrel therapy. Furthermore, high platelet reactivity under clopidogrel is associated with suboptimal coronary flow in STEMI patients undergoing primary PCI. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Harapan Kita Honor Research Grant

Elevated Serum Levels of Alkaline Phosphatase and the Risk of Low Responsiveness to Clopidogrel.

The elevated serum levels of alkaline phosphatase (ALP) serve as independent predictors of stent thrombosis after percutaneous coronary intervention (PCI). Our study aims at investigating the relationship between the serum ALP and the responsiveness to clopidogrel. Patients undergoing elective PCI were enrolled for the study, and all participants received a 300-mg clopidogrel loading dose. The responsiveness to clopidogrel was determined by thromboelastography (TEG), and low responsiveness to clopidogrel was defined based on two aspects: (1) adenosine diphosphate (ADP) -induced platelet-fibrin clot strength (MAADP) of > 47 mm and (2) ADP-induced platelet inhibition rate of < 50%. A logistic regression model analysis was used to calculate the risks of responsiveness to clopidogrel as odd ratios (OR) and 95% confidence intervals (CIs). Overall, 809 patients were considered for the study. They were divided into four quartile groups based on the serum ALP levels. A positive linear trend was observed in MAADP across the ALP quartiles (P for linear trend < 0.001), whereas ADP-induced platelet inhibition rate decreased across the ALP quartiles (P for linear trend = 0.007). When multiple confounders were adjusted, the highest ALP quartile correlated with an increased risk of low responsiveness to clopidogrel compared to the lowest ALP quartile (OR, 1.423; 95% CI, 1.017-1.991; P = 0.039). In the sensitivity analysis, the association remained significant for different definitions of low responsiveness to clopidogrel. The elevated serum levels of ALP are independently associated with an increased risk of low responsiveness to 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&lt;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&lt;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.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Association of ABCB1 Gene Polymorphisms and Clopidogrel Responsiveness in Iranian Patients undergoing Percutaneous Coronary Intervention.

Clopidogrel is an antiplatelet agent currently used for preventing stent thrombosis. Despite certain clinical benefits of clopidogrel in patients undergoing percutaneous coronary intervention (PCI), adequate antiplatelet effect has not been obtained in some patients. The present study was designed to investigate the potential association of ABCB1 (ATP-Binding Cassette, Subfamily B, member1) gene polymorphism, and clopidogrel responsiveness in Iranian patients after PCI. Sixty-seven patients were included in the study. Blood samples were taken from patients at baseline, 2 h after administration of 600-mg loading dose of clopidogrel, 24 h and 30 days after PCI. Platelet aggregation was measured by light transmittance aggregometry (LTA) with two levels of adenosine diphosphate (ADP) concentrations (5 and 20 µM). ABCB1 genotyping was performed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). The allelic frequencies of wild type, heterozygote, and homozygote genotypes of ABCB1 were 20.9%, 74.6%, and 4.5%, respectively. There was no significant association between polymorphism of ABCB1 and clopidogrel non-responsiveness (P > 0.05) in various situations. No significant difference was observed for demographic characteristics. Genetic and demographic factors had no significant effect on the platelet activity of clopidogrel in an Iranian population.

Is There Safety in the Use of Clopidogrel Loading Dose in Patients Over 75 Years of Age with Acute Coronary Syndrome?

Abstract Background: There is limited evidence in the literature regarding the administration of clopidogrel to acute coronary syndrome (ACS) in patients over 75 years of age. Most studies excluded this age group, making the subject controversial due to the increased risk of bleeding in this population. Objective: This is a retrospective, unicentric, and observational study aimed at assessing whether the administration of clopidogrel loading dose increases bleeding rates in patients over 75 years of age. Methods: Patients were divided into two groups: group I: 75 mg of clopidogrel; group II: 300-to 600-mg loading dose of clopidogrel. A total of 174 patients (129 in group I and 45 in group II) were included between May 2010 and May 2015. Statistical analysis: The primary outcome was bleeding (major and/or minor). The secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). The comparison between groups was performed through Q-square and T-test. The multivariate analysis was performed by logistic regression, being considered significant p < 0.05. Results: Comparisons between groups I and II showed differences in the prevalence of diabetes (46.5% vs. 24.4%, p = 0.01), arterial hypertension (90.7% vs. 75, p = 0.01), dyslipidemia (62% vs. 42.2%, p = 0.021), ST segment elevation (11.6% vs. 26.6%, p = 0.016) and coronary intervention percutaneous (16.5% vs. 62.2%, p < 0.0001), respectively. In the multivariate analysis, significant differences were observed between groups I and II in relation to the occurrence of bleeding (8.5% vs. 20%, OR = 0.173, 95% CI: 0.049 - 0.614, p = 0.007). Conclusion: A loading dose of 300 mg or more of clopidogrel.

Impact of Omega-3 Supplementation on High Sensitive C-Reactive Protein Level and 30-Day Major Adverse Cardiac Events After the Implementation of Coronary Stent in Patients with Chronic Kidney Disease: A Randomized Clinical Study.

Purpose: Studies have revealed that patients with chronic kidney disease (CKD) are more susceptible to adverse effects of percutaneous coronary intervention (PCI). In addition, the role of elevated high sensitive C-reactive protein (hs-CRP) in the prediction of adverse cardiac outcomes after coronary stent implantation has already been shown. Therefore, in this study, we aimed to evaluate the effect of omega-3 supplementation on hs-CRP and 30-day major adverse cardiac events (MACE) in patients with CKD undergoing elective PCI.Methods: In this randomized trial, 80 CKD patients who were candidates for elective PCI, were randomly assigned to two groups; the first group received a single dose of omega-3 (2500 mg, 12 h before PCI) as well as the standard drug regimen of PCI and the second group received placebo plus the standard therapy (325 mg loading dose of aspirin, 600 mg loading dose of clopidogrel, and weight-adjusted intravenous heparin). Hs-CRP levels were measured at baseline and 24 h after the intervention as a primary endpoint. The secondary endpoint was the incidence of MACE over a 30-day period after PCI.Results: Omega-3 did not significantly decrease post-PCI serum level of hs-CRP; however, the overall 30-day MACE was significantly lower in the omega-3 group compared to the control group (p=0.05).Conclusion: Our results revealed the positive effect of the omega-3 supplement on decreasing 30-day MACE; hence, omega-3 may be considered as an effective adjunctive therapy to the standard drug regimen used before PCI. The evaluation of the effect of omega-3 on long-term MACE is recommended for future studies.

Association of Gene Polymorphisms in CYP2C19, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients undergoing percutaneous coronary intervention

ObjectiveTo investigate the association of polymorphisms in CYP2C19, platelet reactivity, and the SYNTAX score on 1-Year major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS) undergoing primary percutaneous intervention (PCI) treated with clopidogrel. Material and MethodsOut of 84 ACS patients enrolled, data of 72 patients were finalised for genetic analysis. 59 patients were on Clopidogrel and follow up done for one year. All patients undergoing primary PCI received aspirin 325mg/day indefinitely and a 600-mg loading dose of Clopidogrel followed by 75mg/day for 12 months. Platelet aggregation was determined using a platelet aggregometer (chronology).>46 and <19 HPR (high platelet reactivity) and LPR in the setting of PCI have been defined by the (ROC) curve. Genetic analysis of CYP2C19 by PCR-RFLP technique was done. Syntax score (SS) was independently assessed by two experienced interventional cardiologists who were blinded to all other clinical data. ResultsHPR determined at 1 month was associated with significantly higher rates of MACE between 1 month and 1year in patients in the upper SYNTAX score but not in those in the lower group. CYP2C19*2 was associated with HPR and it was not independently associated with the risk of MACE. ConclusionHPR is associated with increased rates of ischemic event only in patients with high SS suggesting a possible setting in which platelet function testing could be implemented to optimise antiplatelet therapy. CYP2C19*2was the only genetic variant significantly associated HPR but not associated with the risk of MACE.

Association between high on-treatment platelet reactivity to clopidogrel and hepatosteatosis in patients undergoing elective stent implantation.

The present study is an investigation of the association between high on-treatment platelet reactivity to clopidogrel (HTPRC) and hepatosteatosis in patients who had elective stent implantation due to coronary artery disease. A total of 190 consecutive patients who underwent an elective coronary stent implantation due to coronary artery disease were prospectively enrolled in the study. Eligible patients were given a 300 mg loading dose of clopidogrel before percutaneous coronary intervention. All of the patients underwent an ultrasound assessment for fatty liver. The patients were divided into 2 groups according to the detection of HTPRC: patients with HTPRC and patients without HTPRC. HTPRC was present in 54.2% (103 of 190 patients) of the total study population. The age and body mass index data were similar between the 2 groups. In all, 111 (58.6%) patients had hepatosteatosis. The HTPRC ratio was statistically higher in female patients (p=0.032). Hepatosteatosis was significantly greater in patients with HTPRC (p<0.001); 84 (81.6%) patients with HTPRC had hepatosteatosis (p=0.001). There was also a statistically significant association between the hepatosteatosis grade and HTPRC (p<0.001). The percentage of HTPRC was greater in patients with ≥grade 2 hepatosteatosis than grade 1 (p<0.001). Logistic regression analysis indicated that hepatosteatosis (odds ratio: 9.403, 95% confidence interval: 4.519-19.566; p<0.001), fasting blood glucose, and hypertension were independent predictors of HTPRC. To the best of our knowledge, this is the first study to demonstrate a relationship between hepatosteatosis and HTPRC.

Safety and Efficacy of a 600-mg Loading Dose of Clopidogrel 24 Hours Before Pipeline Embolization Device Treatment.

Clopidogrel/aspirin antiplatelet therapy routinely is administered 7-10 days before pipeline aneurysm treatment. Our study assessed the safety and efficacy of a 600-mg loading dose of clopidogrel 24 hours before Pipeline Embolization Device (PED) treatment. We performed a retrospective cohort study involving patients treated with pipeline from October 2010 to May 2016. A total of 39.7% (n= 158) of patients were dispensed a loading dose of 650 mg of aspirin plus at least 600 mg of clopidogrel 24 hours preceding PED deployment; 60.3% (n= 240) received 81-325 mg of aspirin daily for 10 days with 75 mg of clopidogrel daily preprocedurally. The mean follow-up was 15.8 months (standard deviation [SD] 12.4 months). modified Rankin Scale (mRS) was registered before the discharge and at each follow-up visit. To control confounding, we used multivariable logistic regression and propensity score conditioning. Of 398 patients, the proportion of female patients was ≈16.5% (41/240) in both groups and shared the same mean of age ≈56.46 years. Similarly, ≈12.2% (mean= 0.09; SD= 0.30) had a subarachnoid hemorrhage. A total of 92% (mean= 0.29; SD= 0.70) from the pretreatment group and 85.7% (mean= 0.44; SD= 0.91) of the bolus group had a mRS ≤2. In a multivariate analysis, bolus did not affect the mRS score, P= 0.24. Seven patients had a long-term recurrence, 2 (0.83%; mean= 0.01; SD= 0.10) from the pretreatment group. In a multivariable logistic regression, bolus was not associated with a long-term recurrence rate (odds ratio [OR] 1.91; 95% confidence interval [CI] 0.27-13.50; P= 0.52) neither with thromboembolic accidents (OR 0.99; 95% CI 0.96-1.03; P= 0.83) nor with hemorrhagic events (OR 1.00; 95% CI 0.97-1.03; P= 0.99). Three patients died: 1 who received a bolus had an acute subarachnoid hemorrhage. The mean mortality rate was parallel in both groups ≈0.25 (SD= 0.16). Bolus was not associated with mortality (OR1.11; 95% CI 0.26-4.65; P= 0.89). The same associations were present in propensity score-adjusted models. In a cohort receiving PED, a 600-mg loading dose of clopidogrel should be safe and efficacious in those off the standard protocol or showing <30% platelet inhibition before treatment.

Plasma miR-142 accounting for the missing heritability of CYP3A4/5 functionality is associated with pharmacokinetics of clopidogrel.

To investigate whether plasma miRNAs targeting CYP3A4/5 have an impact on the variance of pharmacokinetics of clopidogrel. The contribution of 13 miRNAs to the CYP3A4/5 gene expression and activity was investigated in 55 liver tissues. The association between plasma miRNAs targeting CYP3A4/5 mRNA and clopidogrel pharmacokinetics was analyzed in 31 patients with coronary heart disease who received 300 mg loading dose of clopidogrel. Among 13 miRNAs, miR-142 was accounting for 12.2% (p = 0.002) CYP3A4 mRNA variance and 9.4% (p = 0.005) CYP3A5 mRNA variance, respectively. Plasma miR-142 was negatively associated with H4 Cmax (r = -0.5269; p = 0.0040) and associated with H4 AUC0-4h (r = -0.4986; p = 0.0069) after 300 mg loading dose of clopidogrel in coronary heart disease patients. miR-142 could account for a part of missing heritability of CYP3A4/5 functionality related to clopidogrel activation.

The no-reflow phenomenon in the young and in the elderly

BackgroundThe objectives of this study were to evaluate the incidence of no-reflow as independent predictor of adverse events and to assess whether baseline pre-procedural treatment options may affect clinical outcomes. MethodsData were derived from the ISACS-TC registry (NCT01218776) from October 2010 to January 2015. No-reflow was defined as post-PCI TIMI flow grades 0–1, in the absence of post-procedural significant (≥25%) residual stenosis, abrupt vessel closure, dissection, perforation, thrombus of the original target lesion, or epicardial spasm. The outcome measure was in-hospital mortality. ResultsNo-reflow was identified in 128 of 5997 patients who have undergone PCI (2.1%). On multivariate analysis, patients with no-reflow were more likely to be older (OR: 1.20, 95% CI: 1.01–1.44), to have a history of hypercholesterolemia (OR: 1.95, 95% CI: 1.31–2.91) and to be admitted with a diagnosis of STEMI (OR: 2.96, 95% CI: 1.85–4.72). Angiographic characteristics associated with no-reflow phenomenon were: stenosis ≥50% of the right coronary artery, presence of multivessel disease and pre-procedural TIMI blood flow grades 0–1. No-reflow was highly predictive of in-hospital mortality (17.2% vs. 4.2%; adjusted OR: 4.60, 95% CI: 2.61–8.09). Administration of pre-procedural unfractioned heparin or 600mg clopidogrel loading dose was associated with less incidence of no-reflow (OR: 0.65, 95% CI: 0.43–0.99 and 0.61, 95% CI: 0.37–1.00, respectively). Aspirin, enoxaparin, and 300mg clopidogrel loading dose, did not significantly impact the occurrence of the no-reflow. ConclusionsWe found that pre-procedural administration of 600mg loading dose of clopidogrel and/or unfractioned heparin is associated with reduced incidence of no-reflow.

Clinical effect of ticagrelor administered in acute coronary syndrome patients following percutaneous coronary intervention.

The aim of the present study was to retrospectively analyze the clinical effect and safety of ticagrelor administration in acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI). In total, 203 patients were enrolled, who were confirmed with ACS between March 2013 and May 2013, and had successfully undergone PCI. The patients were randomly divided into two groups, including the clopidogrel (group A, n=108) and ticagrelor groups (group B, n=95). Patients in group A were treated with a 600 mg loading dose of clopidogrel followed by 75 mg/day clopidogrel plus 100 mg/day aspirin. Patients in group B received a 180 mg loading dose of ticagrelor followed by 90 mg ticagrelor twice daily plus 100 mg/day aspirin. Light transmission aggregometry was performed to measure the platelet aggregation rate prior to and following 4 weeks of anti-platelet drug treatment. In addition, the rate of cardiovascular events and the adverse drug reactions were recorded within a 1-year treatment period. Compared with the clopidogrel group, the rate of recurrent angina in the ticagrelor group was significantly lower (P=0.05). However, the rate of dyspnea in the ticagrelor group was significantly higher when compared with that in the clopidogrel group (P=0.03). After 4 weeks of treatment, the reduction in the platelet aggregation rate was significantly different between the two groups (P<0.05). Therefore, ticagrelor, which is a novel antiplatelet aggregation drug, may reduce the rate of the adverse cardiovascular events in ACS patients following PCI, but a higher incidence of side-effects, such as dyspnea, may be observed.

Relationship between pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing percutaneous coronary intervention: comparison between vasodilator‐stimulated phosphoprotein phosphorylation assay and multiple electrode aggregometry

ESSENTIALS: The reliability of platelet tests as markers of the variable bioavailability of clopidogrel is not yet defined. Kinetics of clopidogrel active metabolite (CAM) and platelet response were studied in ischemic heart disease. CAM plasma maximum concentration (Cmax ) predicted vasodilator-stimulated phosphoprotein (VASP-P). Timely performed VASP-P, not an aggregation-based test, may be a surrogate for clopidogrel bioavailability. The high inter-individual variability in the inhibition of platelet function by clopidogrel is mostly explained by high variability in its transformation to an active metabolite (CAM). Objective We investigated the relations between pharmacokinetics and pharmacodynamics of CAM by comparing two methods of platelet function. We enrolled 14 patients undergoing percutaneous coronary interventions for non-ST-segment elevation acute coronary syndrome or inducible myocardial ischemia. Plasma concentrations of clopidogrel and CAM, phosphorylation of vasodilator-stimulated phosphoprotein (VASP-P), expressed as a platelet reactivity index (PRI) and whole-blood platelet aggregation (multiple electrode aggregometer, MEA) were measured before and after a 600-mg clopidogrel loading dose (nine time-points) and before and after 75-mg maintenance doses on days 2, 7 and 30. Plasma concentrations of clopidogrel and CAM were highly variable. CAM reached maximal concentration (Cmax ) (median, 110.8 nm; range, 41.9-484.8) 0.5-2 h after the loading dose. A sigmoid dose-response curve defined the relations between CAMCmax and PRI after 3 to 24 h (IC50 , 459.6 nm; 95% confidence interval, 453.4-465.7; R(2) = 0.82). PRI was unchanged from baseline in patients with the lowest CAMCmax (< 83 nm, n = 7), indicating low sensitivity of VASP-P. PRI values were also predicted by CAMCmax at days 2, 7 and 30. Platelet aggregation measured by MEA did not show significant relations with either PRI or with CAM pharmacokinetics at any time-point. After 600 mg clopidogrel, VASP-P, but not whole-blood platelet aggregation measured by MEA, is almost entirely predicted by CAMCmax . VASP-P could be useful in studies aimed at investigating relations between CAM bioavailability and clinical events.

Changes of High Sensitivity C-Reactive Protein During Clopidogrel Therapy in Patients Undergoing Percutaneous Coronary Intervention

Background:The crucial role of inflammation in the development and progression of atherosclerosis has been previously described. However, there is insufficient data available to demonstrate the changes in high sensitivity C-reactive protein (hs-CRP) during clopidogrel therapy.Objectives:In the present study, we aimed to assess the changes in the inflammatory marker of coronary heart disease, i.e., hs-CRP during clopidogrel therapy, in patients undergoing percutaneous coronary intervention (PCI). We also evaluated the anti-inflammatory effects of clopidogrel, if any, in different groups of patients.Patients and Methods:The study population included 650 consecutive patients who underwent elective, urgent, or emergent PCI. Patients received a 300-mg loading dose of clopidogrel (Plavix®) and aspirin either 24 hours before the planned PCI, or immediately before the procedure in patients with urgent or emergent PCI, followed by a 75-mg daily maintenance dose for up to 12 weeks. At the end of the 12th week, hs-CRP was re-assessed.Results:Six hundred-fifty patients including 386 (59.4%) male and 264 (40.6%) female subjects were enrolled in the study. The mean hs-CRP level was 15.36 ± 9.83 mg/L with a median of 14 mg/L (interquartile range 8 to 19.6 mg/L). Female, hypertensive, diabetic, and non-smoking patients had higher reductions in hs-CRP in response to clopidogrel therapy compared to male, non-hypertensive, non-diabetic and smoker patients, respectively (all P < 0.005). The changes in the hs-CRP levels were also statistically different in patients with various index events before PCI (P < 0.001). No significant differences were observed in the mean reduction of hs-CRP between the patients without stent implantation and those with bare metal or drug-eluting stents (P = 0.07), respectively.Conclusions:We found that the use of clopidogrel in patients undergoing PCI had favorable effects on the suppression of hs-CRP. This effect appears to be heightened and more apparent in some group of patients with co-morbidities such as diabetes and hypertension.

Abstract 16683: Pretreatment With Clopidogrel In ST-segment Elevation Myocardial Infarction. Evidence From a Meta-analysis

Background: Current ACC/AHA guidelines recommend a P2Y12 inhibitor in addition to aspirin in ST-segment elevation myocardial infarction (STEMI) patients either on presentation or in the cardiac catheterization laboratory (CCL). In contrast, European guidelines recommend P2Y12 inhibitor administration as soon as possible, but acknowledge that there is no enough evidence to support this class I recommendation. Aim: Perform a meta-analysis to examine the hypothesis that pretreatment with clopidogrel in STEMI patients is superior to no pretreatment and CCL administration. Methods: We performed a literature search for full length articles comparing clopidogrel administration on presentation (pretreatment) compared with CCL administration in STEMI patients undergoing percutaneous coronary intervention (PCI). We used odds ratio (OR) and random effects model for comparisons. We report mortality, major adverse cardiovascular events (MACE), major bleeding and reinfarction at 30 days. Results: A total of 8 studies with 32,509 STEMI patients were included in the analysis. 30 day mortality was significantly lower with pretreatment compared to CCL administration, 4% vs 5% (OR 0.62, 95% confidence interval (CI) [0.46, 0.83]; P=0.002). MACE was significantly lower with pretreatment compared to CCL administration, 6.8% vs 6.3% (OR 0.69, 95% CI [0.58, 0.83]; P&lt;0.0001). Major bleeding was also lower in the pretreatment group (OR 0.80, 95% CI [0.65, 0.97]; P=0.03) that was driven by one study which used more glycoprotein IIb/IIIa inhibitors and more 600 mg loading dose of clopidogrel in the no pretreatment arm. There was no significant difference in reinfarction rates between the groups, 2.6% vs 3.1%. Conclusion: Clopidogrel administration at presentation for STEMI patients undergoing PCI decreases 30 day major adverse cardiovascular events and improves mortality.

The STIB score: a simple clinical test to predict clopidogrel resistance

Background High platelet reactivity (HPR) to clopidogrel is associated with an increased risk of ischaemic complications during and after coronary interventions and concerns up to 50% of patients undergoing PCI.Aim of the study The aim of the study was to identify patients with HPR to clopidogrel using bedside clinical information obtained in the Stent Thrombosis In Belgium (STIB) trial.Methods Data on platelet reactivity using the VerifyNow® point-of-care assay were obtained in 844 patients undergoing PCI for stable coronary artery disease 12 to 24 hours after a 600-mg loading dose of clopidogrel was given. Demographic, clinical and baseline routine biological tests were obtained and compared with P2Y12 reaction units (PRU). Patients with PRU > 230 (HPR) were considered as non-responders to clopidogrel.Results HPR was observed in 424/844 pts. Age, weight, body mass index (BMI), HPR to aspirin, diabetes, renal failure (MDRD < 60 ml/min), haemoglobin (Hb), haematocrit, fi brinogen, glycaemia and glycated haemoglobin were associated with HPR to clopidogrel. In multivariate analysis, only Hb (OR: 0.77), BMI (OR: 1.06) and diabetes (OR: 1.62) emerged as independent risk factors. Hb < 13.9 g/dl, BMI > 28 kg/m2 and presence of diabetes were equally associated to predict HPR and can be added to derive a simple score to predict clopidogrel resistance.Although 38.5% of patients without a single clinical predictor still have HPR, 2/3 patients with 2 or 3 risk factors are resistant to clopidogrel.Conclusions STIB HPR score allows identifi cation of patients with a high probability of resistance to clopidogrel based on diabetes, Hb < 13.9 g/dl and BMI < 28 kg/m2. This bedside clinical test could be useful for the identifi cation of patients in whom another P2Y12 inhibitor should be recommended before and after PCI.

Prediction of high risk of non-adherence to antiplatelet treatment.

Dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is the standard of care for secondary prevention. Premature discontinuation of clopidogrel is associated with an increased risk of myocardial infarction (MI) or death, and greater health care expenditure. To develop an objective method for identification of patients with high risk of non-adherence to clopidogrel after MI. A total of 189 patients were enrolled into a prospective, observational, single-centre study with a nine-month follow-up. Patients received a 600-mg loading dose and 75-mg maintenance dose of clopidogrel in combination with ASA doses of 300 mg and 75 mg, respectively. Adenosine diposphate-induced platelet aggregation (ADP-PA) was assessed during baseline hospitalisation and at three, six, and nine months after discharge. Adherence to medication with clopidogrel was defined as the proportion of drug availability based on data from the National Health Fund regarding prescribed drug purchases. Adherence was arbitrarily judged adequate when the proportion exceeded 80%. According to our hypothesis, ADP-PA in non-adherent patients should be higher at follow-up visits (at least once) as compared with measurement at hospitalisation. Based on the ROC curve analysis, the optimal cut-off point equal to 4 U was defined (p < 0.0001, 95% CI 0.562-0.654; sensitivity: 60.6%, specificity: 57.1%, positive predictive value: 63.3%, negative predictive value: 54.2%). The prevalence of true adherence to medication in groups of high and low probability of adherence defined according to developed criteria amounted 60 (50.8%) and 23 (32.4%) cases, respectively (p = 0.01). The newly developed method of objective identification of patients with high risk of non-adherence to clopidogrel after MI is easily applicable and cheap, and, despite relatively low sensitivity and specificity, it efficiently differentiates patients with regard to clinical end-points during follow-up.