P A Gurbel

..The mechanisms of the response variability to clopidogrel remain incompletely defined. The contribution of intra- and extracellular pathways are under investigation...

..The aim of this article is to provide a comprehensive and current review of clopidogrel response variability and nonresponsiveness...

..The purpose of this study was to examine the effect of cigarette smoking on the platelet response to clopidogrel...

..04) and between specific inflammation markers (p < or = 0.02). In conclusion, in addition to markedly lowering platelet reactivity to adenosine diphosphate, long-term clopidogrel therapy is associated with an anti-inflammatory effect...

..Spaced administration of a clopidogrel and a single-tablet formulation of aspirin and immediate-release omeprazole (PA32540) was considered as an alternative that might reduce this potential pharmacodynamic interaction...

..Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile...

..A Phase-III TRILOGY trial (NCT00699998) will indicate the clinical efficacy and safety of prasugrel in patients with non-ST-segment elevation ACS, who are medically managed without coronary revascularization...

..Therefore, futher studies are needed to delineate the role of platelet function testing across the spectrum of symptomatic coronary artery disease...

..Future large-scale trials with goals addressing these concerns are needed to define the specific role of PAR-1 receptor inhibitor...

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..Large prospective studies designed to identify which patients are at risk for stent thrombosis on the basis of platelet function testing are under way and may eventually lead to personalized antithrombotic therapy...

..Our primary aim was to determine the degree of platelet aspirin responsiveness in patients, as measured by commonly used methods, and to study the relation of aspirin dose to platelet inhibition...

..The P2Y12 reactivity ratio (PRR) determined by vasodilator-stimulated phosphoprotein phosphorylation levels has been used to indicate the extent of P2Y(12) blockade...

..This study was performed to compare the effects of antiplatelet regimens on early inflammation and cardiac marker release after elective stenting...

..Small scale investigations have suggested that nonresponsiveness may be associated with a heightened risk for adverse clinical events. The above findings have stimulated a close examination of clopidogrel metabolism...

..A higher aspirin dose and strict compliance to therapy may overcome the occurrence of "aspirin resistance" in selected patients. A higher clopidogrel dose may be considered in patients exhibiting clopidogrel nonresponsiveness...

..However, the effect of the clopidogrel loading dose on the rate of thrombin-induced platelet-fibrin clot formation is unknown in this patient population...

..We investigated whether patients who suffered subacute stent thrombosis (SAT) have higher post-treatment reactivity than those who do not encounter stent thrombosis...

..We investigated the relation of high ex vivo platelet reactivity, rapid fibrin generation, and high thrombin-induced clot strength to postdischarge ischemic events in patients undergoing percutaneous coronary intervention (PCI)...

..We determined the effect of clopidogrel dosing on the incidence of nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA)...

..Moreover, limited information is available on the antiplatelet pharmacodynamics of a 300-mg versus a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide with these regimens is unknown...

..These findings may be directly relevant to the effect of alteplase on reperfusion and to future studies using combined platelet inhibitors and thrombolytic therapy...

..The companies were expected to launch the drug in the US by the end of 2008...

..Point-of-service measurements of platelet-fibrin clot characteristics may lead to more intensified antithrombotic therapy and reduced mortality in selected patients...

..Large-scale trials are ongoing that will investigate the role of personalised antiplatelet therapy in the PCI patient...

..However, in the absence of a large-scale prospective clinical trial, routine platelet function monitoring and modification of timing of surgery based on platelet function monitoring are currently not recommended...

..Because both predict cardiovascular events with similar risk ratios, CYP2C19 genotyping and HPR may provide complementary information to stratify risk and personalized DAPT in stented patients than either alone...

..Thus, it is both appropriate and timely to review available data and provide a comprehensive review of ticagrelor...

..Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy...

..Prospective clinical trials to test new algorithms for optimal personalized antiplatelet therapy are needed to provide the evidence base required for the routine adoption of genotyping into clinical practice...

..The antiplatelet effects of the Platelet Inhibition and Patient Outcomes (PLATO) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown...

..This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel...

..16%, P = 0.0004). CONCLUSIONS: HPR is reversibly overcome by a single 60-mg oral dose of elinogrel, a drug now being investigated in a phase 2 trial. CYP2C19*2 was associated with HPR during conventional dual antiplatelet therapy...

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..Larger studies are required to solidify these observations and their clinical relevance...

..The secondary aim was to study the relation of platelet aggregation and TIP-FCS to the occurrence of periprocedural infarction...

..T.E.N.T. Thrombosis Study and future research will likely support the current concepts and lead to personalized treatment regimens that will optimize antiplatelet therapy...

..In the highest risk patients with elevated cardiac biomarkers indicative of myonecrosis, current guidelines support the use of early therapy with glycoprotein IIb/IIIa inhibition, aspirin, and clopidogrel...

..The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy...

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..These finding suggest insufficient platelet inhibition. The clinical importance of these findings should be further investigated to establish the potential link between insufficient platelet inhibition, stent thrombosis, and restenosis...

..Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described...

..However, reduced platelet activation has never been demonstrated in humans. The purpose of the current study was to investigate the effect of heparin coating on platelet activation after coronary artery stenting...

..This finding may be related to superior scaffolding, resulting in a smoother luminal contour after implantation of a closed-cell stent...

..The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial...

..Finally, based on the current evidence platelet reactivity may become a standard of care risk factor measured in all patients with cardiovascular disease...

..We sought to establish an optimal clopidogrel dosing regimen for sustained platelet inhibition in stented patients...

..Marked variability in activation and reactivity were observed despite aspirin therapy...

..However, prospective data on the changes of platelet status in patients before the occurrence of hemorrhagic stroke after thrombolytic therapy are unavailable...

..This review explores the available information linking platelet reactivity during and after PCI to the occurrence of adverse events, including myocardial infarction, recurrent ischemia within 6 months, and stent thrombosis...

..We sought to compare platelet characteristics after reteplase and alteplase therapy in the setting of the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)-III trial...

..Ability of Mg, diltiazem, and leumedins to favorably modulate plasma prostanoid levels have direct clinical implications for the use of these agents in patients with coronary artery disease...

..However, no data are available on the plasma levels of Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1), and platelet-derived osteonectin in this growing population...

..634). The data suggest that the baseline characteristics predict future platelet activity, and may prospectively identify patients who will benefit most from antiplatelet strategies after coronary thrombolysis...

..Elevated P-selectin level also has been observed in the clinical setting of myocardial ischemia and reperfusion; however, its utility in differentiating cardiac from noncardiac origins of chest pain is unknown...

..The ability of MAC to favorably modulate the pre-reperfusion platelet status in such patients is of clinical importance, and further investigation in large-scale clinical trials seem warranted...

..The latter properties of prasugrel may provide a superior alternative to clopidogrel, with less response variability and a decreased prevalence of non-responsiveness...

..Platelets play an important role in the natural history of acute myocardial infarction (AMI)...

..We sought to determine whether the combined measurement of platelet and necrosis markers would improve risk stratification, and yield higher diagnostic utility in patients presenting to the emergency department with chest pain...

..Increased plasma PECAM-1 may serve as a useful marker in the early detection of patients with AMI. Larger studies will be necessary to confirm the utility of soluble PECAM-1 in identifying AMI among patients presenting with chest pain...

..Further investigation of the possible role of PECAM-1 and the relationship between its soluble and platelet fractions in AMI are warranted...

..Enhanced platelet aggregation and receptor expression unquestionably occur after coronary stent implantation; however, the functional characteristics of platelets before stenting have not been fully elucidated...

..This review summarizes the latest and often confusing data on the interaction between fibrinolytic therapy and platelets in certain in vitro, animal and clinical scenarios...

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..We measured platelet characteristics during chronic treatment in patients with coronary artery disease enrolled in the Roxifiban Oral Compound Kinetics Evaluation Trial (ROCKET-I)...

..The documented anti-platelet effects of sertraline and NDMS may be directly related to the mortality benefits of SSRIs after ischemic events including myocardial infarction and stroke...

..Diabetic patients may have a higher prevalence of platelet aspirin resistance than nondiabetic patients. Our goal was to analyze platelet aspirin responsiveness to various aspirin doses in diabetic and nondiabetic patients...

..Further studies are required to investigate the primary mechanisms linking the above processes associated with a prothrombotic state resulting in clinical destabilization of the disease...

..4%) was resistant to aspirin treatment. CONCLUSIONS: Platelet aspirin resistance assessed by methods that directly indicate inhibition of cyclooxygenase is rare in compliant patients with coronary artery disease...

..Taken together, opposite to our expectations, major clinical characteristics of heart failure did not correlate well with the platelet characteristics investigated in this study...

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..These data suggest that VerifyNow may identify a generalized high platelet reactivity phenotype...

..Posttreatment platelet reactivity is a better measure of thrombotic risk than responsiveness to clopidogrel...

..Moreover, knowledge of the mechanisms of cellular crosstalk will lead to important advances in the development of better antithrombotic therapies...

..These findings support a pro-aggregatory state that, in part, explains the thrombotic events shown by epidemiological studies...

..Therefore, the success of fibrinolytic therapy may be dependent on its direct effects on platelets...

..However, the relation of platelet reactivity to glycemic control is less studied in patients on dual antiplatelet therapy...

..We sought to determine whether platelet activity in patients with heart failure is related to an ischemic versus nonischemic etiologic condition, clinical disease severity, or adverse clinical outcomes...

..Long-term aspirin therapy mildly reduces baseline platelet activity; however, this degree of relative platelet inhibition does not appear to be cardioprotective...

..Early identification of vulnerable patients and definition of the role of antiplatelet nonresponsiveness in the development of stent thrombosis should be the focus of future diagnostic and therapeutic strategies...

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..A peak in soluble P-selectin levels at 3 hours after thrombolytic therapy and lower baseline platelet P-selectin were associated with successful thrombolysis...

..If P-selectin is to become a diagnostic tool for differentiating an etiology of chest pain, standardized measurements must be defined for each model of flow cytometer...

..of reversible and irreversible mechanisms of P2Y12 inhibition to bleeding risk, posing the question, "Is it not only how much but how a platelet P2Y12 receptor is inhibited that determines the attributable safety profile?"..

..Baseline angiotensin-converting enzyme inhibitor plus beta-blocker use were associated with lower levels of CRP; no relation was found between CRP levels and aspirin or statin use...

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..Because the prodrug clopidogrel is activated by hepatic cytochrome P450 (CYP) 3A4, we hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity...

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..Further investigation or guidelines are needed to optimize antiplatelet treatment strategies to identify and treat patients resistant to aspirin and/or clopidogrel...

..Nonresponsiveness to clopidogrel treatment has been suggested as a risk factor for the occurrence of ischemic events and stent thrombosis...

..It has fast onset and offset actions that may be advantageous in patients who may have to undergo immediate surgery...