Clopidogrel Response In Patients Research Articles

Clopidogrel Responsiveness in Patients Undergoing Percutaneous Coronary Intervention using Multiplate Analyzer: Frequency and Outcomes

Objectives: Over and under response to dual antiplatelet therapy (DAPT) can lead to bleeding and thrombotic events in patients undergoing coronary stent placement. The present study aimed to assess the platelet response to clopidogrel in patient undergoing percutaneous coronary intervention (PCI) using Multiplate Analyzer. The primary outcome in the present study was the short-term incidence of stent thrombosis and bleeding events. Background: Multiple electrode aggregometry is a rapid and standardized tool to for diagnosis of platelet defects and monitoring response to DAPT. Methods: A hospital-based, prospective study was conducted on 431 patients who underwent PCI from September 2016 to November 2017 and received clopidogrel therapy. The platelet aggregometry was done using a Multiplate analyzer (Dynabyte, Munich, Germany). Patients were followed for 30 days to assess the incidence of stent thrombosis and bleeding. Results: The patients’ mean age was 58 ± 6.7 years. A total of 40% of the patients were diabetic and 7.7% had chronic renal failure. The rate of clopidogrel non-responders was 10.7%, while clopidogrel over-responders were 18.3%. Patients with diabetes and chronic renal failure had significantly lower platelet responsiveness (40.1% with p < 0.05 and 7.7% with p <0.005, respectively). Smoking was significantly associated with platelet over-responsiveness (39.4%, p < 0.001). Patients with low platelet responsiveness to clopidogrel were associated with an increased risk of definite stent thrombosis (p < 0.005), while increasing bleeding risk was significantly associated with over-responsiveness to patients to clopidogrel (p <0.001). Conclusions: Antiplatelet responsiveness showing individual variability with increased risk of stent thrombosis among the cases with no response to the effect of clopidogrel and high risk of bleeding with the over-responsiveness group.

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Background: Previous studies have pointed out the disproportionate action of clopidogrel in inhibiting platelet aggregation due to smoking more than ten cigarettes per a day. This study was designed to examine whether smoking enhances clopidogrel responsiveness in patients who are clinically diagnosed with coronary artery disease (CAD), following percutaneous coronary intervention (PCI). Methods: A total of 324 IHD participants were enrolled in a case-control study. Platelet function test was performed to all participants two hours before PCI procedure to measure clopidogrel response. Participants were then categorized into a non-responder group (case group n = 111) and responder group (control group n = 213). Each group was subdivided into a smoker group and a non-smoker group. All participants received clopidogrel loading dose equivalent to 600 mg and scheduled for elective PCI. Participants’ age, gender, family history of chronic illnesses was recorded in this study. Results: Smoking participants displayed a significant higher level of hemoglobin as compared to the non-smoking participants among the responder and the non-responder study groups (14.6±0.55 vs. 13.12±0.38, P < 0.029; 14.3±0.31 versus 12.96±0.39, P < 0.033) but lower AUC level (17±9 vs. 45±6, P < 0.005; 62±3 vs. 95±7, P < 0.008). Additionally, smoking intensity enhanced clopidogrel responsiveness by odd’s ratio 0.4213 at 95% C.I. (0.259 - 0.684), P < 0.0002. Conclusions: Current smokers had a good response to clopidogrel therapy which exerted a beneficial effect when undergoing PCI as compared to non-smokers. The marked difference in AUC between smokers and non-smokers could be related to the variance in hemoglobin level. The smokers’ paradox needs further justification to confirm this concept.

The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Background: Previous studies have pointed out the disproportionate action of clopidogrel in inhibiting platelet aggregation due to smoking more than ten cigarettes per a day. This study was designed to examine whether smoking enhances clopidogrel responsiveness in patients who are clinically diagnosed with coronary artery disease (CAD), following percutaneous coronary intervention (PCI). Methods: A total of 324 IHD participants were enrolled in a case-control study. Platelet function test was performed to all participants two hours before PCI procedure to measure clopidogrel response. Participants were then categorized into a non-responder group (case group n = 111) and responder group (control group n = 213). Each group was subdivided into a smoker group and a non-smoker group. All participants received clopidogrel loading dose equivalent to 600 mg and scheduled for elective PCI. Participants’ age, gender, family history of chronic illnesses was recorded in this study. Results: Smoking participants displayed a significant higher level of hemoglobin as compared to the non-smoking participants among the responder and the non-responder study groups (14.6±0.55 vs. 13.12±0.38, P < 0.029; 14.3±0.31 versus 12.96±0.39, P < 0.033) but lower AUC level (17±9 vs. 45±6, P < 0.005; 62±3 vs. 95±7, P < 0.008). Additionally, smoking intensity enhanced clopidogrel responsiveness by odd’s ratio 0.4213 at 95% C.I. (0.259 - 0.684), P < 0.0002. Conclusions: Current smokers had a good response to clopidogrel therapy which exerted a beneficial effect when undergoing PCI as compared to non-smokers. The marked difference in AUC between smokers and non-smokers could be related to the variance in hemoglobin level. The smokers’ paradox needs further justification to confirm this concept.

Platelet reactivity after clopidogrel loading in patients with acute ischemic stroke.

ObjectiveIt remains unclear when sufficient antiplatelet effect is achieved after administration of a loading dose of clopidogrel in patients with acute ischemic stroke (AIS). This study aimed to evaluate the clopidogrel response in patients with AIS identified by the platelet function test (PFT).MethodsP2Y12 reaction unit (PRU) values measured using VerifyNow at baseline and at 6, 24, and 72 h after administration of a loading dose (300 mg) of clopidogrel were compared between patients with AIS and those of other cerebrovascular diseases (CVD). The prevalence of clopidogrel abnormal response and its associated factors were examined.ResultsThe PRU value was significantly reduced with time in the other CVD group (p < 0.0001), and also in the AIS group (p = 0.0073). The PRU values were significantly higher in the AIS group than in the other CVD group (p < 0.0001 between the groups, baseline: 314 ± 53 vs. 284 ± 62, p = 0.35; 6 h: 290 ± 66 vs. 214 ± 71, p = 0.016; 24 h: 270 ± 75 vs. 190 ± 70, p < 0.0001; and 72 h: 231 ± 76 vs. 163 ± 93, p = 0.105). The prevalence of clopidogrel hypo-responder (PRU > 240 at 24 h after administration) was higher in the AIS group (79 vs. 33%, p < 0.0001) and associated with the baseline PRU value but not with the cytochrome P450 2C19 genotype or clinical ischemic events.ConclusionsResidual platelet reactivity at 24 h after clopidogrel loading was substantially higher in patients with AIS than in patients with other CVD. In addition, most patients with AIS were judged to be hypo-responders on PFT. This should be carefully interpreted in patients with AIS because of poor specificity for predicting clinical ischemic events.

Influence of GAS5/MicroRNA-223-3p/P2Y12 Axis on Clopidogrel Response in Coronary Artery Disease.

BackgroundDual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest‐specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD.Methods and ResultsA total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of GAS5 single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA‐223‐3p (miR‐223‐3p) expression. Platelet‐rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR‐223‐3p expression. A dual‐luciferase reporter assay was performed to explore the interaction between miR‐223‐3p and GAS5 or P2Y12 3′‐UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG‐01 cells. Loss‐of‐function and gain‐of‐function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR‐223‐3p in MEG‐01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in CYP2C19 poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and P2Y12 mRNA expressions, whereas platelet miR‐223‐3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR‐223‐3p expressions was observed in platelets. MiR‐223‐3p mimic reduced while the miR‐223‐3p inhibitor increased the expression of GAS5 and P2Y12 in MEG‐01 cells. Knockdown of GAS5 by siRNA increased miR‐223‐3p expression and decreased P2Y12 expression, which could be reversed by the miR‐223‐3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR‐223‐3p expression and increased P2Y12 expression, which could be reversed by miR‐223‐3p mimic.Conclusions GAS5 rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the CYP2C19 poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR‐223‐3p.

Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis

Association between CYP3A4 gene polymorphisms and clopidogrel response in patients with cardio-cerebrovascular diseases: a systematic review and Meta-analysis

Frequency of CYP2C19*2 Allele in Patients with Acute Coronary Syndrome: A Cross-sectional Study from Central Kerala, India

Introduction: Ischaemic Heart Diseases (IHD) are increasing at an alarming rate globally. Pharmacotherapy, the mainstay of management of IHD, has Dual Antiplatelet Therapy (DAPT) at its crux. DAPT, comprising of clopidogrel and aspirin, is used often for 12 months in medically managed Acute Coronary Syndrome (ACS). Clopidogrel being a prodrug, needs to be activated after ingestion, mainly by Cytochrome family of enzymes, for the desired pharmacological effects. Abnormal enzymes that convert clopidogrel to its active form can reduce the effectiveness of the drug. Therefore, Single Nucleotide Polymorphisms (SNPs) of the enzymes involved, would predispose the patient to therapy failure and recurrence of the illness. This study aims at identifying the presence of a genetic variant associated with clopidogrel responsiveness in patients with ACS. Aim: To estimate the frequency of CYP2C19*2 allele in patients with ACS presenting to Government Medical College, Thrissur, Kerala, India. Materials and Methods: Present study was a cross-sectional study done among 60 patients who presented to Government Medical College, Thrissur with ACS, between June 2018 to June 2019. Having obtained informed consent from the participants blood samples were collected in Ethylene diamine tetra-acetic Acid (EDTA) tubes. Samples were used to look for presence of CYP2C19*2 allele by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Out of 60 patients 38 were males and 22 were females. Most common age group was 61-65 years. The frequency of CYP2C19*2 allele was 41% in the study population and the variant genotype (AA/AG) was present in 62%. Conclusion: The variant genotype was found to be present in a high frequency in the study population implying the high risk for therapy failure in the study population. This asserts the need to probe the matter further, as the gene is also implicated in the metabolism of several other drugs. The introduction of pharmacogenomic testing prior to initiation of therapy may be therefore recommended for better treatment outcome. However, to validate the same, further studies with larger sample size may be necessary.

Association of fractalkine with functional severity of heart failure and impact on clopidogrel efficacy in patients with ischemic heart disease

IntroductionPatients with heart failure (HF) display elevated levels of soluble fractalkine, a chemokine involved in inflammation processes, atherosclerosis and platelet activation. Further, fractalkine has been associated with reduced pharmacodynamic (PD) responsiveness to clopidogrel. The aim of this study was to investigate the association of fractalkine with the severity of HF and its impact on platelet activation and clopidogrel response in patients with coronary artery disease (CAD) with and without HF. Materials and methodsThis prospective PD study included 116 stable CAD patients on DAPT with aspirin and clopidogrel. Subjects were classified in two groups: patients with HF and reduced (<40%) left ventricular ejection fraction (HFrEF group, n = 56) and patients without HF (no HF group, n = 60). Clinical severity of HF was graded according to NYHA classification. Platelet function assays included vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry and light transmittance aggregometry. Fractalkine and P-selectin concentrations were determined by ELISA. ResultsFractalkine levels progressively increased with the severity of the disease in the HFrEF group (NYHA I: 471.2 ± 52.4 pg/ml, NYHA II: 500.5 ± 38.4 pg/ml, NYHA III: 638.9 ± 54.3 pg/ml, p for linear trend 0.023). Numerically higher concentrations of fractalkine were observed in the HFrEF group compared to the no HF group with borderline significance (p = 0.052). No significant differences in clopidogrel-induced platelet inhibition according to fractalkine values were observed in any of the groups. ConclusionsFractalkine levels were increased in patients with HFrEF and positively associated with the functional severity of the disease. No evident impact of fractalkine on clopidogrel PD efficacy was found.

Clopidogrel response in patients receiving the nonvitamin K antagonist oral anticoagulants apixaban and rivaroxaban.

Clopidogrel response in patients receiving the nonvitamin K antagonist oral anticoagulants apixaban and rivaroxaban.

Effect of Clopidogrel on Platelet CD Markers in Normal Individuals and in Patients with Untreated Type 2 Diabetes Mellitus.

The objective of this study was to evaluate the effect of clopidogrel response in patients with untreated type 2 diabetes mellitus as compared with normal individuals. One hundred and seven subjects i.e. 32 normal and 75 patients with untreated type 2 diabetes mellitus were enrolled in this study. In the first step, normal subjects as well as diabetic patients were selected and tested for various laboratory parameters and platelets flow cytometry. In the second step, an antiplatelet drug (clopidogrel) was administered for 10 days to each individual enrolled in the study. After 10 days blood samples were collected for platelets flow cytometry. CD41 and CD61 did not show any change after the administration of clopidogrel in resting and activated platelets. CD63 and CD62p positivity was increased in normal and in diabetic patients' platelets after activation with ADP before clopidogrel. It was decreased in normal resting and ADP stimulated platelets after clopidogrel treatment. CD63 and CD62p positivity in resting and ADP stimulated patients' platelets was also decreased after clopidogrel treatment. The change was, however, not as marked as in normal subjects.

CYP2C19 defines clopidogrel response in patients undergoing percutaneous neurointervention procedure.

Resumen del trabajo presentado al 5th Symposium on Biomedical Research: Advances and Perspectives In Pharmacology, Drug Toxicity and Pharmacogenetics, celebrado en Madrid del 15 al 16 de marzo de 2018.

Defining a Clopidogrel Response Cut-Off Value Using Light Transmission Aggregometry Before Pipeline Embolization of Unruptured Intracranial Aneurysms.

The choice of appropriate antiplatelet therapy before the Pipeline Embolization Device (PED) placement is usually guided by platelet function testing such as light transmission aggregometry (LTA). In this study, we aimed to define the optimal threshold LTA value for clopidogrel responsiveness to predict the risk of postprocedural thromboembolic complications and to help guide appropriate antiplatelet regimen. A prospectively maintained database at an academic neurosurgical center in the United States was retrospectively analyzed from 2014 to 2017 to identify patients with unruptured intracranial aneurysms treated with the PED. Clinical and radiographic data were analyzed to identify thromboembolic complications in the context of platelet function testing performed by LTA. A total of 95 procedures were performed for PED placement to treat 110 unruptured intracranial aneurysms. Thromboembolic complications were encountered in 4 (4.2%) of these patients. After stratifying the complication rate based on the maximal extent of platelet aggregation after administration of an exogenous platelet agonist, a marked increase in thromboembolic events was observed in patients with LTA values greater than 50%. When LTA was dichotomized based on this value, patients with an LTA value less than 50% had a thromboembolic complication rate of 1.3% (1/80), compared with 20% (3/15) for those with LTA values ≥50% (P= 0.001). We observed the greatest increase in the rate of thromboembolic complications with LTA values of ≥50%. This can serve as an appropriate cut-off value for determining the clopidogrel response in patients undergoing endovascular treatment with the PED.

Potential Usefulness of Clopidogrel Pharmacogenetics in Cerebral Endovascular Procedures and Carotid Artery Stenting.

Previous reports have shown inadequate response to dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in 5-30% of patients undergoing percutaneous coronary interventions (PCI), due mostly to clopidogrel resistance. This prevalence increases up to 66% in patients undergoing neurointerventional procedures. However, clinical significance of CYP2C19 genotypes in neurointerventional procedures or carotid artery stenting (CAS) is unknown. The purpose of this review is to update our current knowledge and understanding of the pharmacogenetic basis for poor clopidogrel responsiveness in patients undergoing CAS and endovascular interventions as well as to explore usefulness of genotyping to reduce the rate of procedure-related thrombosis that results in ischemic complications. A literature search for pharmacogenetic studies in cerebral endovascular interventions and CAS was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers. The review included 7 papers involving 3 genetic polymorphisms on CYP2C19 and 442 subjects. Patients harboring at least one loss-of-function CYP2C19 polymorphism (e.g., CYP2C19*2 and *3) are at an increased risk of thromboembolic complications such as stent thrombosis following neurointerventional procedures. Notably, patients who carry the gain-of-function CYP2C19*17 allele may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Studies assessing the influence of CYP2C19 polymorphisms on high on-treatment platelet reactivity in CAS and cerebrovascular disease patients are still limited and need further validation in large multicenter studies. This review covers an important topic in the field of antiplatelet therapy for cerebral endovascular procedures and CAS.

Anti-platelet drugs, pharmacogenomics and stent thrombosis: What’s new?

Stent thrombosis is a catastrophic complication of percutaneous coronary intervention (PCI) and is associated with a mortality of 25 to 40%. The perception that stent thrombosis is very low in all patients has resulted in a lack of adherence to professional guidelines. New data to identify patients at increased risk for stent thrombosis are emerging. Clopidogrel is a prodrug and the activation of clopidogrel is dependent on CY2C19. Numerous alleles of CYP2C19 exist. The allele CYP2CP*2 has been associated with a marked decrease in platelet responsiveness to clopidogrel. Heterozygote carriers of the CYP2C19*2 have a 2.7 fold increased risk and homozygotes a 4.8 fold increased risk of stent thrombosis. Prospective randomised clinical trials will be necessary to determine the efficacy of CYP2C19 genotype directed therapy in evidence-based clinical decision making. Point-of-care platelet-function tests are becoming available and some centres are now performing such tests on their PCI patients. The most recent AHA/ACC /SCAI guidelines recommend testing for clopidogrel responsiveness in patients at high risk of subacute stent thrombosis and recommend increasing the dose of clopidogrel in non-responders.

Pharmacogenetics of CYP2C19 genetic polymorphism on clopidogrel response in patients with ischemic stroke from Saudi Arabia.

Objective:To elucidate the degree of genetic polymorphisms CYP2C19 (CYP2C19*2, CYP2C19*3) of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel response in patients with acute ischemic stroke from Saudi Arabia.Methods:A case-control study carried out at Neurology Clinics at Asser Central Hospital, Abha, Kingdom of Saudi Arabia from October 2015 to January 2016 and included 25 stroke patients responding to clopidogrel therapy and 25 stroke patients non responding to clopidogrel monotherapy. After obtaining their informed consent, the blood samples were collected and genotyped for CYP2C19 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Allele frequencies were derived from genotypic data and platelet aggregation was measured using multiple electrode aggregometry on the multiplate analyser. Chi Square tests, p-values, odds ratio (OR) and corresponding confidence intervals were calculated for each polymorphism.Results:The CYP2C19*2 (681G>A) and CYP2C19*3 (636 G>A) polymorphism were seen to be in Hardy–Weinberg equilibrium and showed significant allelic and genotypic association between responders and non-responders to clopidogrel (p<0.01). The CYP2C19*2: allelic chi-square=21.49, p=0.000036, OR=5.52 (2.42-12.83); Genotypic Chi-square=10.27, p=0.001, OR=7.88 (1.78-9.73). The CYP2C19*3: Allelic chi-square=11.66, p=0.0006, OR=3.45 (1.57-7.70); genotypic chi-square=4.37, p=0.036, OR=3.69 (0.90-5.81). The variant allele (homozygous and homozygous Mutant) showed significant influence on platelet inhibition and the antiplatelet effect of clopidogrel in ischemic stroke.Conclusion:Our findings provide certain evidence on the genetic effect of CYP2C19 on clopidogrel responsiveness in stroke patients from Saudi Arabia.

Pharmacogenetics of CYP2C19 Genetic Polymorphism on Clopidogrel Response in Patients with Ischemic Stroke from Saudi Arabia (P5.213)

Pharmacogenetics of CYP2C19 Genetic Polymorphism on Clopidogrel Response in Patients with Ischemic Stroke from Saudi Arabia (P5.213)

Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.

SummaryBackgroundDespite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis.MethodsOne hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA).ResultsGenotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01).ConclusionsThe CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.

Mean Platelet Volume and Prognosis of Unstable Angina

Objective: Clopidogrel therapy is the standard of care in patients with unstable angina. However, a percentage of subjects are nonresponders to clopidogrel and this leads to increased adverse outcome. On the other way round, some responsive patients are exposed to bleeding complications. Detection of both in daily practice is important in order to tailor the treatment protocol. In this study we aimed to estimate the cutoff value of mean platelet volume (MPV) for both platelet responsiveness and bleeding risks. Methods: The study was planned as a prospective cohort study. A total number of 230 patients admitted to our CCU with unstable angina over a period of one year (from June 2013 to May 2014) were enrolled. Exclusion criteria were: severe anemia, throm-bocytopenia, myelodysplastic syndrome, coagulopathy and recent blood transfusion. In all patients clopidogrel was initially started and maintained during the hospital stay. Blood (2 ml) was collected in dipotassium EDTA tubes from all patients on the first day of admission by a clean puncture. Samples for MPV analysis were drawn on admission, and analyzed within 1 hour of admission after sampling by Beckman Caulter LH 780 Analyzer. Grouping was then done according to MPV of the patients into group (I) who had a low MPV less than or equal to 7.00 fl, and group (II) with MPV equal to or higher than 9.00 fl. Demographical and clinical variables of the patients were recorded. Routine laboratory parameters were also recorded. Clinical manifestations during the admission period were meticulously reported. Major complications as bleeding or, urgent need for percutaneous coronary intervention (PCI) were also studied. Results: Among the 230 patients analyzed, 175 patients (76%) were found to have MPV ≤7.00 fl (group (I)) and 55 patients (24%) had MPV ≥9.00 fl (group (II)) with mean ± SD MPV (8.4 ± 1.5 fl, vs 11.7 ± 1.2 fl respectively) (p < 0.001). Observation of clinical course during admission period revealed a statistically more significant clinical deterioration in group (II) than group (I) and the presence of more frequent AMI cases in group (II) having a high MPV. A high cutoff value of 9.7 fl for MPV was detected in prediction of clopidogrel nonresponsiveness (group (II)) with a sensitivity of 78.2% and specificity of 66.8%, and a low cutoff value for bleeding tendency lower than 6.3 fl was detected in group (I) with a sensitivity of 71.4% and specificity of 62.5%. Conclusion: This study showed that MPV can be used as a simple bedside predictor for detection of clopidogrel response in patients with unstable angina. And a cutoff value for both platelet responsiveness and risk of bleeding is now reached. This may lead to enhancement in our decision for early intervention and attention for bleeding risk during clopidogrel therapy.

Joint effects of CYP2C19*2 and smoking status on clopidogrel responsiveness in patients with acute coronary syndrome

Joint effects of CYP2C19*2 and smoking status on clopidogrel responsiveness in patients with acute coronary syndrome

Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction

Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction.The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders.The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit.Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.