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Ischemic stroke and myocardial ischemia in clopidogrel users and the association with CYP2C19 loss-of-function homozygocity: a real-world study

The Pharmacogenomics Journal volume 21, pages 402–408 (2021)Cite this article

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Abstract

Reduced clopidogrel effectiveness in preventing recurrent myocardial ischemia following percutaneous coronary intervention has been demonstrated in CYP2C19 loss-of-function carriers. Less is known about the effect of CYP2C19 genotype on the effectiveness of clopidogrel for stroke prevention, particularly in Caucasians. This is a retrospective cohort study, in which we used the Clalit clinical database to follow genotyped clopidogrel initiators, for up to 3 years. Endpoint was a new primary discharge diagnosis of ischemic stroke; secondary endpoints were new primary discharge diagnoses of coronary angioplasty, myocardial infarction (MI), or a composite endpoint of: stroke, MI, or coronary angioplasty. After 3 years of follow up over 628 clopidogrel initiators, 2 out of 12 (16.7%) poor metabolizers, 9 out of 144 intermediate metabolizers (6.3%), and 29 out of 472 (6.1%) normal/rapid/ultrarapid metabolizers have been newly diagnosed with ischemic stroke. Poor metabolizer status was associated with higher risk for ischemic stroke, marginally significant in univariate analysis and in multivariable models; and higher risk for the composite outcome of stroke, myocardial infarction and coronary angioplasty, HR = 3.32 (1.35–8.17) p = 0.009, 2.86 (1.16–7.06) p = 0.02 (univariate and multivariate analyses, respectively). Poor metabolizer status was associated with higher risk for stroke HR = 5.80 (1.33–25.24) p = 0.019, HR = 4.13 (0.94–18.13) p = 0.06 (univariate and multivariate analyses, respectively) in patients who “survived” the first year, and were in the cohort 1–3 years. Caucasian treated with clopidogrel who are homozygote for the CYP2C19 loss-of function allele might be at increased risk for ischemic stroke, and for the composite outcome of ischemic stroke, myocardial infarction and coronary angioplasty.

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Fig. 1: Cumulative event-free survival for the composite outcome of ischemic stroke, myocaridal infarction, and coronary angioplasty, stratified according to CYP2C19 genotype and compared by the log-rank test.

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Authors and Affiliations

  1. Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel

    Naomi Gronich, Idit Lavi, Flavio Lejbkowicz, Mila Pinchev, Walid Saliba & Gad Rennert

  2. Ruth and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel

    Naomi Gronich, Walid Saliba & Gad Rennert

  3. Department of Neurology, Lady Davis Carmel Medical Center, Haifa, Israel

    Yusri Zoabi

  4. Department of Neurology, Rabin Medical Center, Petach Tikva, Israel

    Eitan Auriel

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel

    Eitan Auriel

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Gronich, N., Lavi, I., Lejbkowicz, F. et al. Ischemic stroke and myocardial ischemia in clopidogrel users and the association with CYP2C19 loss-of-function homozygocity: a real-world study. Pharmacogenomics J 21, 402–408 (2021). https://doi.org/10.1038/s41397-021-00218-8

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