Clinical importance of aspirin and clopidogrel resistance

Fehér, Gergely; Fehér, Andrea; Pusch, Gabriella; Koltai, Katalin; Tibold, Antal; Gasztonyi, Beáta; Papp, Elõd; Szekeres, L.; Késmárky, Gábor; Tóth, Kálmán

doi:10.4330/wjc.v2.i7.171

Cited by 56 publications

(44 citation statements)

References 123 publications

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“…However, since a clinical significant interaction cannot be completely excluded, Food and Drug Administration (FDA) recommends avoiding omeprazole and esomeprazole in patients treated with clopidogrel [34]. It has been suggested that there is a possible pharmacokinetic interaction between clopidogrel and statins [31]. There is some evidence that this interaction is more likely with lipophilic statins -simvastatin [37], atorvastatin [38,39] and lovastatin [40], which share the same CYP metabolizing isoenzyme, CYP3A4.…”

Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

“…There are also methods that can be used to measure activation dependent modifications or activation markers, on the surface of platelets. These tests include the assessment of platelet surface P-selectin levels, activated GPIIb/IIIa and platelet -leukocyte clumping [31]. Despite its complex sample preparation and high costs [76], the flow cytometry technique is favoured due to the fact that it uses whole blood, small sample volumes, has a wide range of applications and high accuracy and a good correlation with LTA [77].…”

Section: Flow Cytometrymentioning

confidence: 99%

“…Concurrent administration of nonsteroidal anti-inflammatory drugs (e.g. ibuprofen, indomethacin) may interfere with aspirin's anti-thrombotic effect by blocking its docking site on COX-1 [31]. Proton pump inhibitors (PPIs), that suppress gastric acid secretion, may reduce the bioavailability of aspirin due to inactivation of the drug by gastrointestinal mucosal esterases thus reducing its absorption [32].…”

Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

“…Vasodilator, stimulated phosphoprotein (VASP) phosphorylation, is a method that measures activation-dependent platelet signalling. It is the most specific test used to assess the extent to which P2Y12 receptors are functionally blocked by a P2Y12 antagonist [31]. There are also methods that can be used to measure activation dependent modifications or activation markers, on the surface of platelets.…”

Section: Flow Cytometrymentioning

confidence: 99%

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Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low-or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

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Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

Section: Reduced Bioavailability Of Anti-platelet Drugsmentioning

confidence: 99%

Section: Flow Cytometrymentioning

confidence: 99%

See 2 more Smart Citations

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Mărginean

Bănescu

Scridon

et al. 2016

The Journal of Critical Care Medicine

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“…Specifically, resistance to clopidogrel might be more closely associated with thrombosis after CAS. 21,22) Furthermore, a study indicated that additional administration of cilostazol in clopidogrelresistant patients reduced platelet aggregation, significantly decreasing the incidence of new ischemic lesions on DWIs after CAS. 23) In the present study, triple antiplatelet therapy was administered in the perioperative phase, which might have significantly inhibited thrombus formation even with the appearance of LDA after CAS, contributing to the absence of symptomatic lesions.…”

Section: Discussionmentioning

confidence: 99%

Evaluation and Management of In-stent Low-density Area on CTA after Carotid Artery Stenting at Subacute Phase

Сузукі

Hattori

Itô

et al. 2018

JNET

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Objective: We examined the prognosis and background factors associated with in-stent low-density areas (LDAs) on CTA in the subacute phase after carotid artery stenting (CAS). Materials and Methods:Among 175 lesions for which CAS was performed between April 2008 and September 2016, 100 lesions for which CTA were conducted in the subacute phase after CAS were included for retrospective analysis.Results: Low-density areas were observed in 36 (36.0%) of the 100 lesions. All patients received conservative medical treatment. There was no patient with new neurologic symptoms in the subacute phase. In most lesions, peak stenosis rate was observed relatively early, which gradually declined after 1 week. Low-density areas were observed and the stenosis rate was relatively high in all patients with plaque protrusion immediately after CAS. The use of open-cell stents significantly increased the formation of LDAs. Most LDAs were consistent at the level of the previous most stenotic sites. Conclusion:Low-density areas in the subacute phase after CAS were relatively frequent. In this study, the course was asymptomatic in all patients, and remission was gradually achieved. However, LDAs may have been associated with serious ischemic complications in the subacute phase, as reported in the literature. Therefore, medical treatment, involving intensive antithrombotic therapy, and careful follow-up should be considered.

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Prospective Determination of Aspirin Sensitivity in Patients Resistant to Low Dose Aspirin: A Proof of Concept Study

Westphal

Rainka

Amsler

et al. 2018

The Journal of Clinical Pharma

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This study tested the capability of an assay to predict aspirin response and reduce ischemic events, and healthcare costs, and delays to optimal treatment. Patients who needed aspirin in the course of normal medical care were included. Patients were excluded if they had disorders affecting platelet function, alcohol use within 24 hours of a test, or NSAID use. Dose escalation of chewable aspirin from 81 mg, to 162 mg, to 325 mg daily occurred based on the results of whole blood impedance aggregation testing to the agonists, collagen (1ug/mL, 5 ug/mL) and arachidonate (0.5 mM) after 10-14 days of treatment. The experimental in vitro test was conducted in triplicate by performing aggregometry on samples spiked to a concentration of 10 uM of aspirin in 0.05% dimethyl sulfoxide. Of the 36 patients who were compliant 16 were found to be resistant to the antiplatelet effects of 81 mg daily aspirin. Nine of these patients were predicted to stay resistant despite dose increase. Once tested at higher doses, ten remained resistant. Seven of the 16 patients were predicted to become sensitive to a higher dose while six actually did. Predicted response to increased doses of aspirin was in good agreement with actual response. Sensitivity of the assay was 83% and specificity was 80%. Results are promising and indicate that it is possible to predict, with reasonable accuracy, if a patient will have an adequate platelet response to aspirin or if the patient will never respond to aspirin necessitating an alternative antiplatelet regimen. Larger, multisite studies are inevitably needed.

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Clinical importance of aspirin and clopidogrel resistance

Cited by 56 publications

References 123 publications

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities

Evaluation and Management of In-stent Low-density Area on CTA after Carotid Artery Stenting at Subacute Phase

Prospective Determination of Aspirin Sensitivity in Patients Resistant to Low Dose Aspirin: A Proof of Concept Study

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