Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot

Kołtowski, Łukasz; Tomaniak, Mariusz; Aradi, Dániel; Huczek, Zenon; Filipiak‬, Krzysztof J.; Balsam, Paweł; Gajda, Sylwia; Opolski, Grzegorz

doi:10.5603/cj.a2017.0026

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…3 The number of patients who are resistant to clopidogrel may be up to 35% of the population, which depends on the method of testing and the borders of high residual platelet reactivity. 5 A genotypebased antiplatelet therapy, as observed in a number of observational and randomized trials, is capable of overcoming high residual platelet reactivity [6][7][8][9] and may lead towards a decrease in the number of adverse cardiovascular events. [8][9][10][11][12][13][14][15][16] These results are proven by the results of a metaanalysis of 9000 patients on clopidogrel: the carriership of low function allelic variants increases the risk of major adverse cardiovascular events (MACE) 1.5-fold and the risk of stent thrombosis 2.8-fold.…”

Section: Introductionmentioning

confidence: 99%

CYP2C19*17 May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban

Sychev

Батурина

Мирзаев

et al. 2020

PGPM

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The aim of this study is to assess the influence of gene CYP2C19, CYP3A4, CYP3A5 and ABCB1 polymorphisms on clopidogrel antiplatelet activity, rivaroxaban concentration equilibrium, and clinical outcomes among patients with acute coronary syndrome and non-valvular atrial fibrillation. Methods: In the multicenter prospective registry study of the efficacy and safety of a combined antithrombotic therapy 103 patients with non-valvular atrial fibrillation both undergoing or not a percutaneous coronary intervention were enrolled. The trial assessed the primary outcomes (major bleeding, in-hospital death, cardiovascular death, stroke\transient ischaemic attack, death/renal insufficiency) and secondary outcomes (platelet reactivity units (PRU), rivaroxaban concentration). Results: For none of the clinical outcomes when combined with other covariates, the carriership of polymorphisms CYP3A5*3 rs776746, CYP2C19*2 rs4244285;*17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738 was significant. None of the markers under study (CYP3A5*3 rs776746, CYP2C19*2 rs4244285, *17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738) has proven to affect rivaroxaban equilibrium concentration in blood plasma among patients with atrial fibrillation and acute coronary syndrome. Conclusion: In situations of double or triple antithrombotic rivaroxaban and clopidogrel therapy among patients with atrial fibrillation and acute coronary syndrome, the genetic factors associated with bleeding complications risk (CYP2C19*17) may prove to be clinically relevant.

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Section: Introductionmentioning

confidence: 99%

CYP2C19*17 May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban

Sychev

Батурина

Мирзаев

et al. 2020

PGPM

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“…According to a recent RCT, both genotyping (CYP2C19) and PFT (VerifyNew p2Y12 assay) all resulted in an improved platelet inhibition [25].…”

Section: Discussionmentioning

confidence: 99%

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

Zhang

Zhan

et al. 2018

Cardiol J.

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Background: The preventive effects of laboratory personalized antiplatelet therapy (PAPT) strategy including genetic detection and platelet function testing (PFT) on major adverse cardiac events (MACEs (RR 0.60, p = 0.008) and myocardial infarctions (RR 0.43, p = 0.02) compared to the non-PAPT group. No statistically significant difference was observed between the two groups regarding cardiovascular death (RR 0.77, p = 0.21), bleeding events (RR 0.96, p = 0.59) and ischemic stroke (RR 0.81; p = 0.57). The preventive effect on MACEs was more significant in patients with high on-treatment platelet reactivity (RR 0.46; p = 0.006). Conclusions: Coronary artery disease patients after stenting could obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128-141)

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“…9,10 Multiple prospective studies investigated the impact on platelet reactivity as a surrogate measure of clinical outcomes. [31][32][33][34] A recent pragmatic, randomized trial of CYP2C19 genotyping implementation demonstrated that return of genetic test results influenced antiplatelet therapy prescribing after PCI. 35 In addition, multiple nonrandomized 36,38 and randomized trials 39,41 have examined the impact of genotype-guided-antiplatelet therapy on clinical outcomes.…”

Section: Clinical Outcomes Of Genotype-guided Antiplatelet Therapy Afmentioning

confidence: 99%

Clinical Utility of CYP2C19 Genotype-Guided Antiplatelet Therapy in Patients at Risk of Adverse Cardiovascular and Cerebrovascular Events: A Review of Emerging Evidence

Gower

Ratner

Williams

et al. 2020

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In patients undergoing percutaneous coronary intervention (PCI), the standard of care is dual antiplatelet therapy with a P2Y 12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin. Current clinical practice guidelines now recommend more potent P2Y 12 inhibitors (prasugrel or ticagrelor) over clopidogrel in acute coronary syndrome (ACS). However, clopidogrel remains the most commonly prescribed P2Y 12 inhibitor in the setting of PCI and is also the preferred agent in the treatment and secondary prevention of stroke. Clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. It has been shown that clopidogrel use in patients who are CYP2C19 no function allele carriers are associated with impaired antiplatelet inhibition and a higher risk of major adverse cardiovascular and cerebrovascular events. Compared to clopidogrel, prasugrel and ticagrelor clinical response is not impacted by CYP2C19 genotype. Even with a demonstrated increased risk of adverse outcomes in CYP2C19 no function allele carriers treated with clopidogrel, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial and has not been widely adopted. Recent results from multiple prospective randomized and nonrandomized clinical trials investigating the use of CYP2C19 genotypeguided antiplatelet therapy following PCI have advanced the evidence base demonstrating the clinical utility of this strategy. Multiple recent studies have examined the effects of CYP2C19 genotype on clopidogrel outcomes in the setting of stroke and neurointerventional procedures. In this review, we discern the clinical utility of using CYP2C19 genotype testing to guide antiplatelet therapy prescribing by evaluating the impact of CYP2C19 genotypeguided selection of antiplatelet therapy on clinical outcomes, summarizing emerging data from cardiovascular and neurology clinical studies, and discussing implications for clinical practice guidelines, remaining knowledge gaps and future research directions.

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Optimal aNtiplatelet pharmacotherapy guided by bedSIDE genetic or functional TESTing in elective PCI patients: A pilot study: ONSIDE TEST pilot

Abstract: Background: Dual antiplatelet therapy (DAPT) is recommended after elective percutaneous coronary intervention (PCI) in PFT (36.5 ± 47 PRU) arms as compared to the control arm (176 ± 67.8 PRU), p = 0.01 and p = 0.03, respectively. PMI appeared in 17 (37%) (Cardiol J 2017; 24, 3: 284-292)

Cited by 11 publications

References 33 publications

<p><em>CYP2C19*17</em> May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban</p>

<p><em>CYP2C19*17</em> May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial Fibrillation Who Receive Clopidogrel and Rivaroxaban</p>

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials

<p>Clinical Utility of CYP2C19 Genotype-Guided Antiplatelet Therapy in Patients at Risk of Adverse Cardiovascular and Cerebrovascular Events: A Review of Emerging Evidence</p>

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