Pre-Procedural Platelet Reactivity After Clopidogrel Loading in Korean Patients Undergoing Scheduled Percutaneous Coronary Intervention

Kang, Min-Kyung; Jeong, Young‐Hoon; Yoon, Seong-Eun; Koh, Jin‐Sin; Kim, In-Suk; Park, Yongwhi; Hwang, Seok-Jae; Kwak, Choong Hwan; Hwang, Jin‐Yong

doi:10.5551/jat.4564

Cited by 15 publications

(14 citation statements)

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“…Previous reports, such as genome-wide association studies, demonstrated that the antiplatelet effect of clopidogrel is mostly influenced by the CYP2C19 genotype 11,16) ; however, the genotyping of CYP2C19 cannot precisely predict the antiplatelet effect of clopidogrel. Some EM and IM patients can sometimes be poor responders in a real clinical setting 8,15) .…”

Section: Discussionmentioning

confidence: 99%

“…Patients are classified by CYP2C19 enzymatic activities into 3 groups, extensive metabolizer (EM) ( 1/ 1; wild type), intermediate metabolizer (IM) ( 1/ 2 or 1/ 3), and poor metabolizer (PM) ( 2/ 2, 3/ 3, or 2/ 3). Notably, the frequency of PMs is higher in Asians (-20%) than Caucasians (3-5%) [13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

“…In patients with CYP2C19 SNPs, the antiplatelet effect of clopidogrel is insufficient due to reduced plasma concentration of the active metabolite of clopidogrel [15][16][17] ; therefore, patients with CYP2C19 SNPs are associated with a higher incidence of cardiovascular events [17][18][19] . Determination of CYP2C19 genotypes is important to predict the risk of cardiovascular events for the use of clopidogrel.…”

Section: Introductionmentioning

confidence: 99%

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Prediction of Clopidogrel Low Responders by a Rapid CYP2C19 Activity Test

Tazaki

Jinnai

Tada

et al. 2012

JAT

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Aim: Clopidogrel, an essential drug for the prevention of stent thrombosis, is a prodrug activated by CYP enzyme family including CYP2C19. It is known that activity-defective polymorphisms of CYP2C19 (CYP2C19 2 and 3) are associated with reduced clopidogrel efficacy and poor prognosis. Recently, the 13 C-pantoprazole breath test is developed to evaluate the CYP2C19 activity. The aim of this study is to evaluated the efficiency of the CYP2C19 activity test as a predictor of antiplatelet effect of clopidogrel Methods: The CYP2C19 activity and the antiplatelet effect of clopidogrel were evaluated in 27 healthy volunteers. Change of the carbon isotope ratios ( 13 CO2/ 12 CO2) in expiration gas between before and after 13 C-pantoprazole intake was evaluated as delta over baseline (DOB) ratio (‰).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prediction of Clopidogrel Low Responders by a Rapid CYP2C19 Activity Test

Tazaki

Jinnai

Tada

et al. 2012

JAT

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“…Studies by us 9) and others 10) examined the antiplatelet effects of clopidogrel in Japanese patients and detected clear effects related to CYP2C19 SNPs. The percentage of people lacking enzymatic activity, designated as poor metabolizers (PM), is 3-5% in Western populations, while approximately 20% in Asians, including Japanese 11,12) ; therefore, CYP2C19 SNPs have a bigger impact on Asians 13) , including Japanese. It is well known that antiplatelet therapy increases the risk of bleeding complications.…”

Section: Ppi Studymentioning

confidence: 99%

Effects of PPIs and an H2 blocker on the Antiplatelet Function of Clopidogrel in Japanese Patients under Dual Antiplatelet Therapy

Yamane

Kato

Tazaki

et al. 2012

JAT

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Aim: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential after percutaneous coronary intervention (PCI).Clopidogrel is a prodrug and changed into active metabolite by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although the degree of its contribution is dependent on the kind of PPI. Omeprazole, a PPI, has been reported to weaken the antiplatelet effects of clopidogrel. Famotidine, a histamine receptor type 2 (H2) blocker, could also be an alternative to PPIs. The aim of this study was to evaluate the effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel. Methods: Patients receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were enrolled (n = 25). The initial PPI was changed to the other PPI as a crossover study. In another study, patients undergoing DAPT without taking PPIs or H2 blockers were enrolled (n = 30) and famotidine was added. Results: Platelet aggregability when taking omeprazole was higher than when taking rabeprazole, evaluated by an optical aggregometer using collagen as a stimulus (p= 0.0051) and by the VerifyNow P2Y12 assay (p= 0.0060). Platelet aggregability when taking rabeprazole was comparable to that in control patients (n= 15). Concomitant use of famotidine had no effect. Conclusion: Omeprazole significantly reduced the antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger than that of rabeprazole. Concomitant use of famotidine had no effect on the antiplatelet effect of clopidogrel.

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“…This effect has been observed with loading dose regimens of 300, 600 mg and higher, and maintenance dosing of 75 and 150 mg [8,20,[28][29][30][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49]. While increased dosing reduces the number of patients with high residual platelet reactivity, not all patients reach an optimal level of platelet inhibition even with higher dosing.…”

Section: E V I D E N C E O F G E N E T I C I M P a C T O N T H I E N mentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of thienopyridines: clinically relevant?

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2011

Fundamemntal Clinical Pharma

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The standard of care for patients following an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is dual antiplatelet therapy with aspirin and a thienopyridine. Thienopyridines are irreversible adenosine diphosphate (ADP) receptor antagonists that inhibit ADP-induced platelet aggregation. Clopidogrel bisulfate (clopidogrel), a P2Y 12 receptor antagonist, is the most commonly prescribed [1,2]. Substantial individual variability in response to clopidogrel exists [3][4][5][6] with reduced levels of inhibition of platelet aggregation associated with an increased risk of cardiovascular events [7][8][9]. The variable response to clopidogrel is multifactorial linked to factors such as age, weight, and comorbid conditions such as diabetes, drugdrug interactions, and genetic variation.Prasugrel hydrochloride (prasugrel), a third-generation thienopyridine and also a P2Y 12 receptor antagonist, achieves greater levels of platelet inhibition with less inter-patient variability [10]. The more efficient metabolism of prasugrel has been reported to contribute to the higher inhibition of platelet aggregation and a more rapid onset of action [11,12]. In the TRITON-TIMI 38 trial, treatment with prasugrel as compared with clopidogrel resulted in a significantly lower rate of ischemic events and more bleeding [10]. D R U G M E T A B O L I Z I N G A N D T R A N S P O R T E R G E N E S A N D T H I E N O P Y R I D I N E R E S P O N S EAlthough both prodrugs require biotransformation, the pathways leading to the pharmacologically active moiety differ between prasugrel and clopidogrel [13][14][15]. Prasugrel is rapidly hydrolyzed during absorption to the thiolactone metabolite R-95913, which is then metabolized primarily by the cytochrome P450 (CYP) genes, CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19 [15][16][17]. This efficiency leads to rapid conversion and generation of greater levels of active metabolite. The relationship between prasugrel active metabolite exposure and maximal platelet aggregation is sigmoidal Prasugrel standard dosing achieves inhibition

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Pre-Procedural Platelet Reactivity After Clopidogrel Loading in Korean Patients Undergoing Scheduled Percutaneous Coronary Intervention

Cited by 15 publications

References 50 publications

Prediction of Clopidogrel Low Responders by a Rapid CYP2C19 Activity Test

Prediction of Clopidogrel Low Responders by a Rapid CYP2C19 Activity Test

Effects of PPIs and an H2 blocker on the Antiplatelet Function of Clopidogrel in Japanese Patients under Dual Antiplatelet Therapy

Pharmacogenetics and pharmacogenomics of thienopyridines: clinically relevant?

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