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Aspirin and clopidogrel resistance: methodological challenges and opportunities
Armen Yuri Gasparyan
Vascular Health and Risk Management , 2010, DOI: http://dx.doi.org/10.2147/VHRM.S9087
Abstract: spirin and clopidogrel resistance: methodological challenges and opportunities Commentary (5935) Total Article Views Authors: Armen Yuri Gasparyan Published Date March 2010 Volume 2010:6 Pages 109 - 112 DOI: http://dx.doi.org/10.2147/VHRM.S9087 Armen Yuri Gasparyan Clinical Research Unit, Russell’s Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, West Midlands, UK Abstract: Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.
Aspirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting  [cached]
Rakesh K Sharma,Hanumanth K Reddy,Vibhuti N Singh,et al
Vascular Health and Risk Management , 2009,
Abstract: Rakesh K Sharma1, Hanumanth K Reddy1, Vibhuti N Singh2, Rohit Sharma1, Donald J Voelker1, Girish Bhatt11Medical Center of South Arkansas, El Dorado, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Bayfront Medical Center, St. Petersburg, University of South Florida, Tampa, FL, USAAbstract: Patients undergoing coronary artery stenting receive an antiplatelet regimen to reduce the risk of antithrombotic complications. Current guidelines recommend the use of acetyl salicylic acid (aspirin) and clopidogrel as evidenced by large clinical trials. There has been a concern about variable responses of patients to aspirin and clopidogrel which may predispose them to subacute stent thrombosis or late stent thrombosis. Up to 25% of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) were found to have hyporesponsiveness or resistance to clopidogrel which may predispose them to recurrent events. Dual antiplatelet regimen is a standard therapy in these patients and there is always a concern about variable responses to aspirin and clopidogrel predisposing them to acute coronary syndrome (ACS). Prevalence of this hyporesponsiveness or resistance may be due to noncompliance, genetic mutations, co-morbid situations and concomitant use of other drugs. This issue is of considerable importance in the era of coronary drug eluting stents when a long-term dual antiplatelet regimen is needed. This paper is a review for clinicians taking care of such patients with hyporesponsiveness or nonresponsiveness to dual antiplatelet regimen.Keywords: aspirin, clopidogrel, acute coronary syndrome, coronary artery stenting
Aspirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting
Rakesh K Sharma, Hanumanth K Reddy, Vibhuti N Singh, et al
Vascular Health and Risk Management , 2009, DOI: http://dx.doi.org/10.2147/VHRM.S6787
Abstract: spirin and clopidogrel hyporesponsiveness and nonresponsiveness in patients with coronary artery stenting Review (6560) Total Article Views Authors: Rakesh K Sharma, Hanumanth K Reddy, Vibhuti N Singh, et al Published Date November 2009 Volume 2009:5 Pages 965 - 972 DOI: http://dx.doi.org/10.2147/VHRM.S6787 Rakesh K Sharma1, Hanumanth K Reddy1, Vibhuti N Singh2, Rohit Sharma1, Donald J Voelker1, Girish Bhatt1 1Medical Center of South Arkansas, El Dorado, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Bayfront Medical Center, St. Petersburg, University of South Florida, Tampa, FL, USA Abstract: Patients undergoing coronary artery stenting receive an antiplatelet regimen to reduce the risk of antithrombotic complications. Current guidelines recommend the use of acetyl salicylic acid (aspirin) and clopidogrel as evidenced by large clinical trials. There has been a concern about variable responses of patients to aspirin and clopidogrel which may predispose them to subacute stent thrombosis or late stent thrombosis. Up to 25% of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) were found to have hyporesponsiveness or resistance to clopidogrel which may predispose them to recurrent events. Dual antiplatelet regimen is a standard therapy in these patients and there is always a concern about variable responses to aspirin and clopidogrel predisposing them to acute coronary syndrome (ACS). Prevalence of this hyporesponsiveness or resistance may be due to noncompliance, genetic mutations, co-morbid situations and concomitant use of other drugs. This issue is of considerable importance in the era of coronary drug eluting stents when a long-term dual antiplatelet regimen is needed. This paper is a review for clinicians taking care of such patients with hyporesponsiveness or nonresponsiveness to dual antiplatelet regimen.
Aspirin and clopidogrel resistance: methodological challenges and opportunities  [cached]
Armen Yuri Gasparyan
Vascular Health and Risk Management , 2010,
Abstract: Armen Yuri GasparyanClinical Research Unit, Russell’s Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, West Midlands, UKAbstract: Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.Keywords: aspirin, clopidogrel, resistance, cardiovascular disease, platelet function tests
Clopidogrel resistance  [cached]
Ye?im Güray,ümit Güray,?ule Korkmaz
Anadolu Kardiyoloji Dergisi , 2009,
Abstract: Platelets play a critical role in pathogenesis of atherothrombotic diseases such as acute coronary syndromes and ischemic stroke. Clopidogrel, a thienopyridine derivative is an effective antiplatelet drug mostly used in combination with aspirin or as a single drug in aspirin intolerant patients. However, despite its proven efficacy in various clinical trials, some patients exhibit impaired response to clopidogrel and have activated platelets while on usual clopidogrel treatment. Although definition and mechanism(s) of this therapeutic failure are poorly understood, it is associated with higher morbidity and mortality as in aspirin resistance. Various causes have been implicated in clopidogrel resistance and alternative therapies are recommended. The aim of this review is to evaluate possible mechanisms, its clinical relevance and alternative treatments of this significant issue.
Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance - The BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan) to improve antiplatelet therapy
Horst Neubauer, Andreas FC Kaiser, Heinz G Endres, Jan C Krüger, Andreas Engelhardt, Sebastian Lask, Fenena Pepinghege, Andreas Kusber, Andreas Mügge
BMC Medicine , 2011, DOI: 10.1186/1741-7015-9-3
Abstract: Platelet function testing using whole blood aggregometry (Chronolog 590) was performed 48 hours following coronary stenting (for either acute coronary syndromes or stable coronary artery disease) on 504 patients. The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low responders (CLR: >5 ohm; adenosine diphosphate (ADP) 5 μM) and/or ASA low responders (ALR: >0 ohm; arachidonic acid 10 μM) were treated according to a structured therapy plan: in the case of CLR, the maintenance + dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ALR was treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification did not take effect sufficiently. In addition, ADP receptor antagonist 2-methylthioadenosine 5'-monophosphate triethylammonium salt (MeSAMP) testing and ASA incubation were performed to rule out either a platelet ADP-receptor defect or an ASA pharmacokinetic resistance.Of the total cohort of 504 patients, we detected 30.8% clopidogrel low-responders and 19.4% aspirin low-responders. For ALR, with a dose adjustment of 300 mg ASA daily, 94.6% of ALR were effectively treated and the residual 5.4% by administration of daily dosages of 500 mg ASA. This means that after modification of the ASA maintenance dose, all initial ALRs had an adequate antiplatelet response.The results for clopidogrel revealed that 69% of the CLR were treated effectively by increasing the clopidogrel dose to 150 mg daily. When prasugrel was not available or contraindicated, 12.7% of the remaining low responders showed an adequate result after being switched to ticlopidine. Consequently, by applying the therapy algorithm, we were able to reduce the CLR prevalence by 86.6%. On including prasugrel in the therapy plan, we were finally able to eliminate
Resistance to antiplatelet drugs (aspirin, clopidogrel) in patients undergoing elective percutaneous coronary intervention  [cached]
V.A. Sulimov,E.V. Moroz
Rational Pharmacotherapy in Cardiology , 2012,
Abstract: Aim. To study prevalence of resistance to acetylsalicylic acid, clopidogrel and dual resistance in percutaneous coronary intervention (PCI), to identify clinical risk factors of resistance development, to study effects of concomitant therapy on resistance development, to identify relationship between risk of cardiovascular complications and activity of platelet aggregation, to assess safety of dual antiplatelet therapy, and to suggest possible ways to overcome clopidogrel resistance.Material and Methods. Patients (n=100) with stable angina class II-IV, that were planned for PCI, were included in the study. Patients randomized to group A (n=53) received clopidogrel 75 mg daily for 7 days before PCI, and later were allocated to subgroups of clopidogrel sensitive or resistant depending on platelet aggregation. In resistant subgroup clopidogrel daily dose was increased to 150 mg for the whole next period of observation. Patients randomized to group B (n=47) received a loading dose of clopidogrel 300 mg one day before PCI. Depending on the results of platelet reactivity assessment, patients were split into sensitive or resistant subgroups. Patients of resistant subgroup received the second loading dose of clopidogrel 300 mg before PCI and started to take clopidogrel 150 mg daily after PCI. Patients of sensitive subgroup did not receive the second clopidogrel loading dose and started to take clopidogrel in usual daily dose of 75 mg. The combined endpoint (after 6 and 12 months) included cardiovascular death, recurrent nonfatal myocardial infarction, recurrent angina, acute ischemic stroke, acute impairment of peripheral circulation.Results. Increased reactivity of platelets to acetylsalicylic acid was detected in 21% of patients. Resistance to clopidogrel in both groups was 56%. Double resistance was registered in 8% of patients. The development of resistance to clopidogrel was related with obesity (p=0.014) and hyperglycemia (p=0.017). 4 and 11 cardiovascular events were registered in 6 and 12 months, respectively.Conclusion. To assess efficacy of antiplatelet therapy it is advisable to study platelet aggregation before and shortly after PCI, especially in patients with obesity and glucose metabolism disturbances. Knowledge of changes in platelet aggregation during clopidogrel therapy can be usefull for timely correction of antiplatelet therapy. Increase in clopidogrel dose up to 150 mg a day is one of the possible way to overcome resistance to clopidogrel.
Boosting platelet inhibition in poor responder to aspirin and clopidogrel undergoing percutaneous coronary intervention: role of tirofiban
Gianluca Campo, Luca Fileti, Marco Valgimigli, et al
Journal of Blood Medicine , 2010, DOI: http://dx.doi.org/10.2147/JBM.S7236
Abstract: oosting platelet inhibition in poor responder to aspirin and clopidogrel undergoing percutaneous coronary intervention: role of tirofiban Review (3494) Total Article Views Authors: Gianluca Campo, Luca Fileti, Marco Valgimigli, et al Published Date May 2010 Volume 2010:1 Pages 61 - 69 DOI: http://dx.doi.org/10.2147/JBM.S7236 Gianluca Campo1, Luca Fileti1, Marco Valgimigli1, Jlenia Marchesini1, Antonella Scalone1, Roberto Ferrari1,2 1Cardiovascular Institute, Azienda Ospedaliera Universitaria S Anna, Ferrara, Italy; 2Cardiovascular Research Centre, Salvatore Maugeri Foundation, IRCCS Gussago (BS), Italy Abstract: Nowadays, aspirin (acetylsalicylic acid) and clopidogrel form the cornerstone in prevention of cardiovascular events and their clinical effectiveness has been well established. The thienopyridine clopidogrel is a prodrug that, after hepatic metabolization, strongly inhibits adenosine diphosphate-induced platelet aggregation. Aspirin is a non-steroidal anti-inflammatory drug that exerts its anti-platelet action through the irreversible acetylation of platelet cyclooxygenase (COX)-1, blocking thromboxane A2 production. However, despite dual-antiplatelet therapy, some patients still develop recurrent cardiovascular ischemic events. Many studies have clearly showed that a marked variability exists in the responsiveness to aspirin and clopidogrel, being the poor responder patients at higher risk of short (peri-procedural) and long-term ischemic complications. In particular, these patients showed a major recurrence of myocardial infarction and, after stent implantation, of stent thrombosis. The mechanisms of aspirin and clopidogrel poor response are numerous and not fully elucidated, and are likely multifactorial (eg, genetic polymorphisms, elevated baseline platelet reactivity, drug interaction). How to improve the short- and long-term outcome of these patients is currently unknown. Recently published and ongoing clinical trials are evaluating different strategies for the acute and chronic treatments (eg, reload of clopidogrel, double clopidogrel maintenance dose, switching to prasugrel). In this paper, we reviewed all available evidence on aspirin and clopidogrel resistance and focused our attention on tirofiban, a glycoprotein IIb/IIIa inhibitor that may be used to obtain a better platelet inhibition in poor responder patients during the acute phase and in particular during percutaneous coronary intervention.
ACC/AHA clopidogrel clinical alert. What must be modern antiplatelet therapy?  [cached]
S.J. Martsevich
Rational Pharmacotherapy in Cardiology , 2010,
Abstract: The ACC/AHA clopidogrel clinical alert about the possibility of ineffective treatment with clopidogrel is discussed. The reason of this resistance to clopidogrel therapy and possible ways to overcome it is considered.
Thrombelastographic haemostatic status and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): assessing and monitoring the antithrombotic effect of clopidogrel and aspirin versus aspirin alone in hypercoagulable patients: study protocol for a randomized controlled trial
Sulman Rafiq, P?r I Johansson, Mette Zacho, Trine Stissing, Klaus Kofoed, Nikolaj B Lilleoer, Daniel A Steinbrüchel
Trials , 2012, DOI: 10.1186/1745-6215-13-48
Abstract: This is a prospective randomized clinical trial, with an open-label design with blinded evaluation of graft patency. TEG-Hypercoagulability is defined as a TEG maximum amplitude above 69 mm. Two hundred and fifty TEG-Hypercoagulable patients will be randomized to either an interventional group receiving clopidogrel 75 mg daily for three months (after initial oral bolus of 300 mg) together with aspirin 75 mg or a control group receiving aspirin 75 mg daily alone. Monitoring of antiplatelet efficacy and on-treatment platelet reactivity to clopidogrel and aspirin will be conducted with Multiplate aggregometry. Graft patency will be assessed with Multislice computed tomography (MSCT) at three months after surgery.The present trial is the first randomized clinical trial to evaluate whether TEG-Hypercoagulable CABG patients will benefit from intensified antiplatelet therapy after surgery. Monitoring of platelet inhibition from instituted antithrombotic therapy will elucidate platelet resistance patterns after CABG surgery. The results could be helpful in redefining how clinicians can evaluate patients preoperatively for their postoperative thromboembolic risk and tailor individualized postoperative antiplatelet therapy.Clinicaltrials.gov Identifier NCT01046942
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