High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values

Leunissen, Tesse; Weem, S.M.O. Peeters; Urbanus, Rolf T.; Ruijter, Hester M. den; Moll, Frans L.; Asselbergs, Folkert W.; Borst, Gert J. de

doi:10.1016/j.ejvs.2016.04.019

Cited by 23 publications

(3 citation statements)

References 38 publications

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“…Moreover, in symptomatic patients undergoing extremity revascularization, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is indicated to prevent limb-related events (restenosis and stent thrombosis) [1]. Unfortunately, up to 83% of patients treated with DAPT have high on-treatment platelet reactivity (HTPR) to clopidogrel, which is a risk factor for MACE [2]. This inter-individual variation in platelet reactivity has been associated with several clinical and genetic variables including body mass index, diabetes mellitus (DM), concomitant use of some drugs, smoking status and variant alleles in the ABCB1, P2RY12, PON1, CES1 and B4GALT2 genes [3–9].…”

Section: Introductionmentioning

confidence: 99%

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Hernández-Suárez

Nuñez-Medina

Scott

et al. 2018

Drug Metabolism and Personalized Therapy

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Background Antiplatelet therapy with clopidogrel is recommended to reduce cardiovascular events in patients with peripheral artery disease (PAD); however, clopidogrel efficacy has not been adequately studied in this patient population. Therefore, we aimed to determine the effects of cilostazol therapy on platelet reactivity among PAD patients on clopidogrel. Methods We performed a cross-sectional pilot study of 46 Puerto Rican patients diagnosed with PAD. The cohort was divided based on use of clopidogrel and cilostazol (n = 24) or clopidogrel alone (n = 22). Platelet function was measured ex vivo using the VerifyNow P2Y12 assay. Genomic DNA was extracted from peripheral blood samples using the QIAamp DNA Blood Midi Kit, which was subjected to candidate variant genotyping (CYP2C19, ABCB1, PON1 and P2RY12) using TaqMan quantitative polymerase chain reaction assays. All analyses were performed using SAS version 9.4 (SAS Institute). Results Among all enrolled patients, 18 (39%) had high on-treatment platelet reactivity (HTPR). The mean platelet reactivity was 207 ± 53 (range, 78–325) with higher P2Y12 reaction units in the non-cilostazol group, 224 ± 45 vs. 191 ± 55 on the cilostazol group (p = 0.03). No significant differences were observed in the clinical or genetic variables between the two groups. A multiple regression analysis determined that history of diabetes mellitus (p= 0.03), use of cilostazol (p = 0.03) and hematocrit (p = 0.02) were independent predictors of platelet reactivity. Conclusions In Puerto Rican PAD patients on clopidogrel therapy, history of diabetes mellitus, use of cilostazol and hematocrit are independent predictors of platelet reactivity. Adjunctive cilostazol therapy may enhance clopidogrel efficacy among PAD patients with HTPR.

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Section: Introductionmentioning

confidence: 99%

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Hernández-Suárez

Nuñez-Medina

Scott

et al. 2018

Drug Metabolism and Personalized Therapy

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“…High on-treatment platelet reactivity has been reported in patients with PAD treated with ASA or P2Y 12 receptor inhibitors (6,7,39). The limitations of this study include that based on the clinical situation of our patients with PAD, we could not analyze the platelet function of these patients without ASA monotherapy, and residual high on-treatment platelet reactivity for ASA was not determined.…”

Section: Discussionmentioning

confidence: 93%

Differential Inhibition of Platelet Reactivity by Dual Therapy With Aspirin and Low-Dose Rivaroxaban in Peripheral Arterial Disease: A Pilot Study

Jurk

Rothenaicher

Groß

et al. 2022

Front. Cardiovasc. Med.

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Patients with peripheral arterial disease (PAD) benefit from combination therapy with acetylsalicylic acid (ASA, 100 mg, one time per day) plus low-dose rivaroxaban (2.5 mg, two times per day) compared to ASA monotherapy. In particular, major adverse cardiac and limb events were significantly reduced after peripheral endovascular revascularization (EVR). In this pilot study, the platelet activation status in vivo and platelet reactivity in vitro were longitudinally analyzed by flow cytometric assays and calibrated automated thrombography in platelet-rich plasma (PRP) from 10 patients with PAD receiving ASA (100 mg, one time per day) before EVR, ASA plus clopidogrel (75 mg, one time per day) after EVR, and ASA plus rivaroxaban (2.5 mg, two times per day) during a long-term follow-up. Platelet responsiveness to clopidogrel was compared to additional 10 patients with stable PAD and clopidogrel (75 mg, one time per day) monotherapy. ASA plus rivaroxaban treatment resulted in a significantly decreased thrombin peak in PRP for two triggers, namely, low concentration of tissue factor (TF) and thrombin, compared to ASA monotherapy. TF-controlled thrombin generation was additionally characterized by a significantly prolonged lag time in PRP and platelet-free plasma during ASA plus rivaroxaban combination therapy. In comparison, ASA plus clopidogrel treatment presented a significant reduction of the thrombin peak in PRP, which was less pronounced than during subsequent ASA plus rivaroxaban therapy. Platelet responsiveness to clopidogrel was observed for 60% of patients receiving ASA plus clopidogrel and clopidogrel monotherapy, respectively. Blocking of CD36 on the platelet surface further reduced the thrombin peak in PRP induced by TF for all three therapy regimes. Platelet activation in vivo and in response to the GPVI-agonist convulxin or thrombin in vitro was similar, whereas integrin αIIbβ3 activation and α-granule release induced by the PAR-1 activating peptide TRAP-6 were significantly diminished during ASA plus rivaroxaban treatment compared to ASA monotherapy. In conclusion, the data of this pilot study indicate an inhibitory effect of rivaroxaban on the thrombin propagation phase of CD36-sensitive platelet thrombin formation in patients with PAD treated with ASA plus rivaroxaban combination therapy, which is associated with decreased PAR-1 but not thrombin-mediated platelet activation.

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“…Tento jednoduchý "point of care" test umožňuje rýchle zhodnotenie účinnosti liečby viacerými protidoštičkovými liekmi z jednej vzorky plnej krvi. Klinická použiteľnosť testu bola opakovane dokumentovaná u pacientov podstupujúcich koronárne (26)(27)(28)(29)(30), neurovaskulárne (14, 31, 32) a periférne cievne intervencie (33).…”

Section: Ako Monitorovať účInnosť Liečby Antagonistami Adp Receptorov V Klinickej Praxi?unclassified

Monitoring and tailoring the P2Y12 ADP receptor blocker therapy

Bolek¹,

Korpallová²,

Urban³

et al. 2020

Vnitr Lek

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Základom farmakologickej liečby u pacientov s akútnym koronárnym syndrómom (AKS) a pacientov podstupujúcich perkutánne koronárne intevencie (PCI) je liečba inhibítormi P2Y12 ADP receptorov. V súčasnosti však pribúdajú informácie o asociácii nedostatočnej odpovede na liečbu inhibítorom P2Y12 ADP receptorov s rizikom vzniku nežiaducich ischemických príhod u pacientov podstupujúcich PCI, vrátane rizika trombózy stentu, ktorá je relatívne vzácnou, ale život -ohrozujúcou komplikáciou. Nedostatočnú účinnosť liečby inhibítormi P2Y12 ADP receptorov je možné v súčasnosti detegovať viacerými laboratórnymi testami, z nich zlatý štandard predstavuje optická agregometria s indukciou adenozíndifosfátom a ako najšpecifickejší test sa javí meranie fosforylácie VASP (vasodilator-stimulated phosphoprotein) prietokovou cytometriou. V prípade detekcie je možné rezistenciu na liečbu inhibítorov P2Y12 ADP receptorov ovplyvniť zmenou dávkovania, zámenou liečby za iný preparát zo skupiny inhibítorov P2Y12 ADP receptorov (napr. zmenou klopidogrelu za prasugrel) alebo pridaním ďalšieho antiagregancia. Ako perspektívne sa tiež javí ovplyvnenie nedostatočnej odpovede podaním parenterálneho P2Y12 ADP receptor inhibítoru -kangreloru. Práca sumarizuje súčasné poznatky o úlohe rezistencie na liečbu inhibítormi P2Y12 ADP receptorov pri vzniku nežiaducich príhod u pacientov podstupujúcich PCI, o možnostiach jej včasnej detekcie a o možnostiach jej terapeutického ovplyvnenia.Kľúčové slová: inhibítory P2Y12 ADP receptorov, perkutánna koronárna intervencia, personalizovaná medicína, vysoká reaktivita trombocytov.Monitoring and tailoring the P2Y12 ADP receptor blocker therapy P2Y12 ADP receptor blocker (ADPRB) treatment forms currently the basis of pharmacotherapy in acute coronary syndrome (ACS) patients, and in patients after percutaneous coronary interventions (PCI). However, nowadays, there are lots of data demonstrating an association between insufficient ADPRB on-treatment response and the risk of ischemic events, including stent trombosis, which is an uncommon but life-threatening complication in patients after PCI. High on-treatment platelet reactivity may be detected with several laboratory tests. Light transsmition aggregometry with ADP induction is so far considered to be a "golden standard", and VASP (vasodilator stimulated phosphoprotein) phosphorylation assessement using flow cytometry is probably the most specific test for the assessment of insuficient platelet response. If high on-treatment platelet reactivity is detected, this phenomenon migh be overcome with increased ADPRB dosing, ADPRB switch (e. g. switch of clopidogrel to prasugrel), or with the addition of other antiplatelet agent. The administration of cangrelor -a new parenteral ADPRB -might be another perspective way how to overcome the phenomenon of insuficient ADPRB on-treatment response. The article summarizes current knowledge about the ADPRB resistance and the risk of ischemic events in patients undergoing PCI, the current approaches for the detection of this resistance...

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High On-Treatment Platelet Reactivity in Peripheral Arterial Disease: A Pilot Study to Find the Optimal Test and Cut Off Values

Abstract: HCPR is present in PAD patients and research on HCPR is needed in this population; timing of tests is relevant and standardisation of tests is needed. The optimal conditions for platelet function testing should be determined.

Cited by 23 publications

References 38 publications

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Effect of cilostazol on platelet reactivity among patients with peripheral artery disease on clopidogrel therapy

Differential Inhibition of Platelet Reactivity by Dual Therapy With Aspirin and Low-Dose Rivaroxaban in Peripheral Arterial Disease: A Pilot Study

Monitoring and tailoring the P2Y12 ADP receptor blocker therapy

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