Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel

Bouman, H. J.; Parlak, E.; Werkum, Jochem W. van; Breet, Nicoline J.; Cate, Hugo Ten; Hackeng, Christian M.; Berg, Jurriën Ten; Taubert, Dirk

doi:10.1111/j.1538-7836.2009.03733.x

Cited by 102 publications

(75 citation statements)

References 27 publications

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“…A strong agreement between aggregation measurements with Verify Now and VASP-test could also be shown by Bidget et al (5). VASP-test and Verify Now also showed the best correlation with the plasma concentration of active Clopidogrel metabolites, so that these two tests were particularly recommended for monitoring Clopidogrelinduced platelet inhibition (10). The VASP test has a very high prognostic value for ischemic events in patients undergoing treatment with P2Y 12 -receptor antagonists following PCI (26).…”

Section: Introductionmentioning

confidence: 70%

Clopidogrel versus Prasugrel in dual Platelet inhibition on elderly patients with acute coronary syndrome – the CLOPRA study

Piper¹

2015

MRAJ

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Our study carried out in elderly and multimorbid patients with acute coronary syndrome initially treated with ASS (100 mg per day) plus Clopidogrel (75 mg per day) was focused at Clopidogrel low-and non-responders. Moreover, we intended to clarify how far patients with reduced Clopidogrel response can profit by switching to Prasugrel.In 178 patients (mean age: 74.1 ± 0.6 years) Thrombocyte Reactivity Indices (TRI) were measured by VASP-tests. Patients showing a limited Clopidogrel response (low-and nonresponders) were switched to Prasugrel (60 mg loading dose followed by 5 or 10 mg maintenance dose per day; 10 mg as standard dose, 5 mg in patients aged 75 years or older or weighting 60 Kg or less). Patients who were switched to Prasugrel were controlled by further VASP-tests. Additional evaluations were made for several subgroups of different age and gender. All patients were treated in a rehabilitation unit (Clinic "Meduna", Bad Bertrich, Germany), VASP-tests were carried out in a specialized laboratory (Center for Laboratory Diagnostics, Koblenz, Germany).In elderly patients the fraction of Clopidogrel low-and non-responders tended to higher proportions than in younger patients (34.8 versus 46.8 %). In all cases with limited Clopidogrel response thrombocyte reactivity could be lowered by switching to Prasugrel. In patients of 75 years or older, or weighting less than 60 KG, a daily dose of 5 mg Prasugrel led to the same sufficient reduction of thrombocyte reactivity as in the other patients given 10 mg per day. After drug-switching circa 6 % remained low-or non responders regardless of whether they were treated with 5 or 10 mg Prasugrel. In patients successfully switched to Prasugrel we found the same reduction of thrombocyte reactivity as in Clopidogrel responders (mean TRI: 19%); all of our patients treated as described were free from any bleeding complications.All in all, Prasugrel seems to be more effective in lowering thrombocyte reactivity also in elderly patients, because the proportion of patients with limited response is much lower than in patients treated with Clopidogrel.

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Section: Introductionmentioning

confidence: 70%

Clopidogrel versus Prasugrel in dual Platelet inhibition on elderly patients with acute coronary syndrome – the CLOPRA study

Piper¹

2015

MRAJ

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“…A previous study showed that LTA, the VASP index, and the VerifyNow-P2Y12 assay were correlated with the in vitro plasma levels of the active metabolite of clopidogrel. 29) Routine monitoring of PRU immediately after TAVI could predict future bleeding events, allowing adjustment of the clopidogrel dose.…”

Section: Discussionmentioning

confidence: 99%

Hyper-Response to Clopidogrel in Japanese Patients Undergoing Transcatheter Aortic Valve Implantation

et al. 2016

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SummaryDual antiplatelet therapy is empirically recommended following transcatheter aortic valve implantation (TAVI). The aims of the present study were to analyze the effect of clopidogrel on platelet function and to determine the relative contribution of each CYP2C19 loss-of-function genotype undergoing TAVI.Thirty-two patients undergoing TAVI and with clopidogrel treatment were studied. All patients were treated with an Edwards SapienXT valve. Platelet reactivity was measured by the VerifyNow P2Y12 point-of-care assay at 7 days and 30 days after the procedure and a cutoff value of 95 PRU was used to identify a hyper-response of platelet reactivity. The Spartan RX TM sample-to-result point-of-care DNA testing system was used to identify CYP2C19 loss-of-function genotypes. Hyper-response of platelet reactivity was identified in 11 (34.3%) patients, although 24 (80%) were carriers of at least one CYP2C19 reduced-function allele. The PRU values did not change significantly from 7 days to 30 days after TAVI (136.7 ± 73.4 versus 150.4 ± 83.2, P = 0.13). The incidences of life-threatening bleeding, minor bleeding, and transfusion were significantly higher among the hyper-response of platelet reactivity group (27.3% versus 0%, P = 0.03, 36.4% versus 4.8%, P = 0.04, 81.8% versus 42.9%, P = 0.04, respectively).A hyper-response to clopidogrel was observed in one-third of patients undergoing TAVI and was related to bleeding events, even though 80% of the patients were carriers of the CYP2C19 reduced-function allele. (Int Heart J 2016; 57: 190-197) Key words: Platelet function tests, Antiplatelet therapy T ranscatheter aortic valve implantation (TAVI) has emerged as a viable therapeutic option for patients with severe symptomatic aortic stenosis (AS). 1,2)However, special attention should be paid to potential periprocedural and early complications, including ischemic (stroke, myocardial infarction) or bleeding (access site complication) events. 3,4) After TAVI, guidelines recommend the use of clopidogrel in addition to aspirin for a 3-to 6-month period. 5-7)While this strategy has been accepted as the usual practice following TAVI, the recommendation remains empirical and prospective controlled trials are lacking. Few data have been reported regarding the effectiveness of clopidogrel in the TAVI setting or its possible impact on adverse events.Results from previous studies in patients treated with clopidogrel have shown wide variability in platelet responsiveness, and high platelet reactivity under clopidogrel treatment has been linked to stent thrombosis and adverse cardiovascular events after coronary stenting. [8][9][10][11][12][13][14] Notably, there exists a subset of patients with a hyper-response to clopidogrel who may be at increased risk of bleeding complications. 15,16) Genetic polymorphism of the CYP2C19 allele, crucial to the metabolism of clopidogrel into its active metabolite, has been implicated as a mechanism of both hyper-and hypo-response. A loss-of-function polymorphism in CYP2C19, known as the CYP2...

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“…Similarly, in our study, patients on adjunctive therapy with GP IIb/IIIa inhibitors when compared with those receiving exclusively aspirin and clopidogrel were numerically more likely to present with HTPR at baseline according to the VASP assay. Not only does the VASP assay facilitate the risk stratification process in ACS patients undergoing PCI [10][11][12][13][14], but according to a recent study, it also provides the best reflection of the in vivo plasma level of the active metabolite of clopidogrel when compared with light transmission aggregometry, Verify-Now ® system, whole blood aggregometry, and the IMPACT-R ADP test [25]. Numerous pharmacodynamic studies including unselected patients in terms of their baseline platelet reactivity demonstrated that prasugrel much stronger than clopidogrel, even with high doses of the latter (i.e.…”

Section: Discussionmentioning

confidence: 99%

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

et al. 2014

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Background: The aim of this study was to assess antiplatelet effect of prasugrel in acute coronary syndrome (ACS) patients with high on-treatment platelet reactivity (HTPR) on clopidogrel, undergoing percutaneous coronary intervention (PCI).Methods : A prospective, platelet reactivity-guided, parallel-group, open-label (70.0 [61.3--75.6] vs. 11.9 [6.8-25.7]%; p < 0.000001) and slightly but significantly rose between 24 h and 30 days (27.9 [15.5-46.8 24 h (25.1 [13.7-40.2] vs. 22.0 [18.4-36.8 (30.3 [20.4-45.7 (Cardiol J 2014; 21, 5: 547-556) ]%; p < 0.0006). In contrast, median PRI values in the clopidogrel group were similar at baseline and at ]%; p = NS) and then modestly rose at 30 days

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Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel

Cited by 102 publications

References 27 publications

Clopidogrel versus Prasugrel in dual Platelet inhibition on elderly patients with acute coronary syndrome – the CLOPRA study

Clopidogrel versus Prasugrel in dual Platelet inhibition on elderly patients with acute coronary syndrome – the CLOPRA study

Hyper-Response to Clopidogrel in Japanese Patients Undergoing Transcatheter Aortic Valve Implantation

Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up

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