Review of aspirin and clopidogrel resistance in peripheral arterial disease

Guirgis, Mina; Thompson, Peter L.; Jansen, Shirley

doi:10.1016/j.jvs.2017.07.065

Cited by 68 publications

(57 citation statements)

References 59 publications

(91 reference statements)

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“…By contrast, it is known that an impaired response to antiplatelet therapy underlies the increased risk of post-operative occlusions and can even result in death after CABG surgery [6]. Several potential explanations have been proposed for the nature of high on-treatment platelet reactivity, including modifiable factors: too low doses of anti-platelet drugs, high platelet turnover, oxidative stress, dyslipidaemia and inflammation [7][8][9][10][11][12]. Coronary artery bypass grafting surgery itself is associated with excessive activation of platelets, which results in stimulation of the production and release of young platelets [2,13,14].…”

Section: Introductionmentioning

confidence: 99%

Platelet reactivity expressed as a novel platelet reactivity score is associated with higher inflammatory state after coronary artery bypass grafting

et al. 2019

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Introduction: Despite therapy, patients operated using a cardiopulmonary bypass demonstrate increased platelet aggregation, which rebounds to above preoperative levels. The aim of the study was to test the interaction between platelet reactivity/activation and selected inflammatory markers in the post-operative period. Material and methods: In total, 103 patients with non-ST elevation acute coronary syndrome (NSTE-ACS) who were not eligible for percutaneous coronary interventions (PCI), and required urgent revascularization, were included. Platelet reactivity was measured using the PFA-100 platelet analyser, multiple electrode aggregometry, and was expressed as a novel platelet reactivity score (PRS). Patients were divided using their PRS scores into high platelet relativity or low platelet reactivity subgroups (HPR or LPR). Platelet basal activation was measured using immunoassays for soluble P-selectin and soluble CD40L. We measured high-sensitivity C-reactive protein (CRP), and used immunoassays for tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) as inflammation markers. Results: Significant differences between HPR and LPR groups were found for CRP (mg/l): 81.5 vs. 44.6, p < 0.02; and TNF-α (pg/l): 3.51 vs. 2.37, p < 0.02. A significant association was found between CRP, TNF-α, IL-6 and platelet reactivity (platelet reactivity score). Cohen's k showed: CRP = 0.49, p < 0.0001, TNF-α = 0.37, p < 0.002. Perioperative myocardial infarction and rhythm disturbances occurred more frequently in the high platelet reactivity group: 7 (16.3%) vs. 2 (3.3%), p < 0.04, and 9 (20.9%) vs. 4 (6.7%), p < 0.04, respectively. Conclusions: Inflammatory parameters CRP and TNF-α are strongly associated with platelet reactivity (expressed as PRS) in cardiopulmonary bypass graft patients. Platelet hyperreactivity in the early post-operative period combined with a systemic inflammatory state correlates with a higher risk of post-operative rhythm disturbances and myocardial infarction.

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Section: Introductionmentioning

confidence: 99%

Platelet reactivity expressed as a novel platelet reactivity score is associated with higher inflammatory state after coronary artery bypass grafting

et al. 2019

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“…[12][13][14][15][16] Resistance to both of these drugs is a well-known phenomenon in people, which has resulted in genetic screening and also a need for PFT. 22,[28][29][30][31] To complicate matters, CKD in people also is associated with resistance to antiplatelet treatment and is a consideration for cardiologists and nephrologists when treating patients with a variety of diseases, but in particular cardiovascular disease. 22,[32][33][34][35][36][37][38][39] Interestingly, a recent study of human patients showed that presence of proteinuria independent of estimated glomerular filtration rate was associated with treatment resistance for clopidogrel, but not aspirin.…”

Section: Discussionmentioning

confidence: 99%

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

Shropshire

Johnson

Olver

2020

Veterinary Internal Medicne

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Background Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs. Objectives Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs. Animals Six healthy and 14 PLN dogs. Methods Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration. Results In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs. Conclusions and Clinical Importance Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

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“…The closest to its definition is LTA, which is the oldest method for evaluating platelet function. However, it is very time‐consuming, and requires skilled technicians and large sample volume, so it is not widely used either in clinical practice or in most scientific publications . Multiplate ® is a far more user‐friendly device, especially in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Multiplate® evaluation of acetylsalicylic acid efficacy in carotid surgery: routine and genetic influencing factors

Roullet

Labrouche

Carrié

et al. 2018

Journal of Thrombosis and Haemostasis

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Background Acetylsalicylic acid (ASA) is recommended before, during and after carotid endarterectomy (CEA). The efficacy of ASA is influenced by numerous biological and genotypic factors. Objectives To determine the biological efficacy of ASA by using the Multiplate method, and to explore the biological parameters and genomic factors influencing this efficacy. Methods This descriptive cross-sectional study included all patients scheduled for CEA between January 2012 and April 2013. Multiplate tests were performed at day 0 and day 30. A set of 66 single-nucleotide polymorphisms (SNPs) from 38 genes or DNA regions were selected and studied along with phenotypic parameters by the use of hierarchical clustering (HC) for multidimensional data management. Results Fifty-five patients receiving ASA were analyzed. Of the patients, 95% were found to be sensitive to ASA, with values under the threshold of normality (400 AU min ). However, there were notable differences in residual aggregation among subjects over a wide range. HC revealed four subclusters comprising three categories of parameters: (i) routine and functional parameters - in ASA-treated patients, the ASPItest was highly linked to the ADPtest, to platelet count, and, to a lesser extent, to fibrinogen and hematocrit; (ii) polymorphisms in genes involved in ASA absorption and in the arachidonic acid pathway (ABCB1 and COX-1); and (iii) polymorphisms in genes modulating basal platelet function, i.e. TBXA2R, ADRA2A, PEAR1, ITGA2 and ITGB1. Conclusion Most patients treated with ASA before CEA were sensitive to it, according to Multiplate ASPItest results. Genomic factors influencing this efficacy are SNPs involved in ASA absorption and metabolic pathway, and in modulations in basal platelet function.

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Review of aspirin and clopidogrel resistance in peripheral arterial disease

Abstract: The limited research addressing AR and CR in PAD suggests that further research is required to clarify the role of platelet assays and potential for individualized antiplatelet therapy.

Cited by 68 publications

References 59 publications

Platelet reactivity expressed as a novel platelet reactivity score is associated with higher inflammatory state after coronary artery bypass grafting

Platelet reactivity expressed as a novel platelet reactivity score is associated with higher inflammatory state after coronary artery bypass grafting

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

Multiplate® evaluation of acetylsalicylic acid efficacy in carotid surgery: routine and genetic influencing factors

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