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Association of CYP2C19 Loss-of-Function Alleles with Major Adverse Cardiovascular Events of Clopidogrel in Stable Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: Meta-analysis

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Abstract

Purpose

It was aimed to determine the aggregated risk of MACE (major adverse cardiovascular events) in stable CAD patients carrying CYP2C19 LoF alleles taking clopidogrel.

Methods

Literature was searched in different databases for relevant studies. Aggregated risk was estimated using a fixed/random effect model where p-value<0.05 was considered statistically significant.

Results

In total, 21 studies with 16,194 stable CAD patients were assessed. It was found that patients treated with clopidogrel carrying either one or two CYP2C19 LoF alleles who underwent PCI were associated with significantly increased risk of MACE compared to non-carriers (OR: 1.71, 95% CI: 1.51–1.94, p<0.00001) that was driven from cardiovascular death (OR: 1.43, 95% CI: 1.02–1.99, p=0.04), myocardial infarction (OR: 1.75, 95% CI: 1.42–2.16, p<0.00001), stroke (OR: 2.30, 95% CI: 1.52–3.47, p<0.0001), and stent thrombosis (OR: 4.08, 95% CI: 2.52–6.61, p<0.00001). It was also found that carriers of two CYP2C19 LoF alleles were associated with a significantly marked risk of MACE than non-carriers (OR: 2.22, 95% CI: 1.60–3.09, p<0.00001). Furthermore, the increased risk of MACE remained markedly significant in Asian patients (OR: 2.03, 95% CI: 1.72–2.40, p<0.00001) and was less significant in western patients (OR: 1.35, 95% CI: 1.11–1.63, p=0.002). Bleeding events were not significantly different in carriers of CYP2C19 LoF alleles compared to non-carriers (OR: 1.11, 95% CI: 0.85–1.45, p=0.43).

Conclusion

Stable CAD patients treated with clopidogrel and carried CYP2C19 LoF alleles undergoing PCI were associated with significantly increased risk of MACE compared to non-carriers, even markedly significant for Asian patients.

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Data Availability

This manuscript does not contain any associated data. However, all raw and processed data used in this analysis will be available upon request.

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  1. Department of Pharmacy, University of Rajshahi, Rajshahi, 6205, Bangladesh

    Mohitosh Biswas & Sumaiya Khatun Kali

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Contributions

MB designed this study and performed all statistical analyses. MB and MSKK were involved in the selection process of studies. Data extraction, input, and analysis were carried out by MB and were double-checked by MSKK. MB drafted this manuscript, and both authors agreed to submit in this journal.

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Correspondence to Mohitosh Biswas.

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Biswas, M., Kali, S.K. Association of CYP2C19 Loss-of-Function Alleles with Major Adverse Cardiovascular Events of Clopidogrel in Stable Coronary Artery Disease Patients Undergoing Percutaneous Coronary Intervention: Meta-analysis. Cardiovasc Drugs Ther 35, 1147–1159 (2021). https://doi.org/10.1007/s10557-021-07142-w

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