Genetic variants of reduced clopidogrel absorption and platelet reactivity after standard clopidogrel therapy and serial dose tailoring in the NCT02096419 trial: a pharmacogenetic substudy

    Authors

    Abstract

    Introduction: Multidrug resistance gene 1 (MDR1) encodes clopidogrel’s intestinal efflux transporter P-glycoprotein. Polymorphism in MDR1 exon C3435C>T has been linked to alterations of clopidogrel absorption and the level of platelet inhibiton. (1-3) Patients and Methods: We performed pharmacogenetic analysis from our previously published trial which evaluated the effect of serial clopidogrel dose adjustment based on continuous platelet function testing in acute coronary syndrome patients with initially determined high on-treatment platelet reactivity on clopidogrel. Fourty-two and fourty-three patients were genotyped for MDR1 C3435T from the control group and the interventional group, respectively. PR levels during 12 month follow up were compared between carriers and non-carriers of loss of function allele 3435T. Results: 3435T carriers and non-carriers had similar PR levels in the interventional group (p=0.460). PR of 3435T carriers was higher compared to noncarriers in the control group, however, not statistically significant (p=0.084) during entire follow up period (**Figure 1**). Figure 1. The effect of MDR1 3435T allele on platelet reactivity. Conclusion: Presence of MDR1 3435T allele was not associated with statistically significant changes in PR in both groups of patients. Larger trials with adequate power are warranted to confirm these results.

    DOI

    https://doi.org/10.15836/ccar.2015.205

    Literature

    1. Taubert D, von Beckerath N, Grimberg G, Lazar A, Jung N, Goeser T, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006;80:486–501. https://doi.org/10.1016/j.clpt.2006.07.007
    2. Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376:1312–9. https://doi.org/10.1016/S0140-6736(10)61273-1
    3. Samardzic J, Krpan M, Skoric B, Pasalic M, Petricevic M, Milicic D. Serial clopidogrel dose adjustment after platelet function testing improves outcome of acute coronary syndrome patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity. J Thromb Thrombolysis. 2014;38:459–69. https://doi.org/10.1007/s11239-014-1087-0
    Cardiologia Croatica
    Back to search

    Genetic variants of reduced clopidogrel absorption and platelet reactivity after standard clopidogrel therapy and serial dose tailoring in the NCT02096419 trial: a pharmacogenetic substudy

    Abstract
    Issue9-10
    Published
    Pages205
    PDF via DOIhttps://doi.org/10.15836/ccar.2015.205

    Authors

    Jure Samardzic*ORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Nada BozinaORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Boško SkoricORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Marijan PašalicORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Lana GanociORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Miroslav KrpanORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Mate PetricevicORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
    Davor MilicicORCIDUnivesity of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia

    *Correspondence email: jure.samardzic@gmail.com

    Abstract

    Introduction: Multidrug resistance gene 1 (MDR1) encodes clopidogrel’s intestinal efflux transporter P-glycoprotein. Polymorphism in MDR1 exon C3435C>T has been linked to alterations of clopidogrel absorption and the level of platelet inhibiton. (1-3) Patients and Methods: We performed pharmacogenetic analysis from our previously published trial which evaluated the effect of serial clopidogrel dose adjustment based on continuous platelet function testing in acute coronary syndrome patients with initially determined high on-treatment platelet reactivity on clopidogrel. Fourty-two and fourty-three patients were genotyped for MDR1 C3435T from the control group and the interventional group, respectively. PR levels during 12 month follow up were compared between carriers and non-carriers of loss of function allele 3435T. Results: 3435T carriers and non-carriers had similar PR levels in the interventional group (p=0.460). PR of 3435T carriers was higher compared to noncarriers in the control group, however, not statistically significant (p=0.084) during entire follow up period (**Figure 1**). Figure 1. The effect of MDR1 3435T allele on platelet reactivity. Conclusion: Presence of MDR1 3435T allele was not associated with statistically significant changes in PR in both groups of patients. Larger trials with adequate power are warranted to confirm these results.

    Literature

    1. 1.
      Taubert D, von Beckerath N, Grimberg G, Lazar A, Jung N, Goeser T, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006;80:486–501.DOI
    2. 2.
      Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376:1312–9.DOI
    3. 3.
      Samardzic J, Krpan M, Skoric B, Pasalic M, Petricevic M, Milicic D. Serial clopidogrel dose adjustment after platelet function testing improves outcome of acute coronary syndrome patients undergoing percutaneous coronary intervention with high on-treatment platelet reactivity. J Thromb Thrombolysis. 2014;38:459–69.DOI