Effects of the CYP2C19 LoF allele on major adverse cardiovascular events associated with clopidogrel in acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Author:

Biswas Mohitosh123ORCID,Sukasem Chonlaphat1245ORCID,Khatun Kali Most Sumaiya3ORCID,Ibrahim Baharudin67ORCID

Affiliation:

1. Division of Pharmacogenomics & Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

2. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand

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

4. Pharmacogenomics & Precision Medicine, The Preventive Genomics & Family Check-up Services Center, Bumrungrad International Hospital, Bangkok, Thailand

5. MRC Centre for Drug Safety Science, Department of Pharmacology & Therapeutics, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, L69 3GL, UK

6. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia

7. Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, 50603, Malaysia

Abstract

The aggregated risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients inheriting CYP2C19 loss-of function (LoF) alleles who underwent percutaneous coronary intervention (PCI) and were treated with clopidogrel is controversial. In the current study, we searched the literature in different databases for eligible studies. The risk ratio (RR) was measured where p<0.05 was statistically significant. The ACS patients with either one or two CYP2C19 LoF alleles who underwent PCI, treated with clopidogrel were correlated with a significantly escalated risk of MACE compared with noncarriers (RR: 1.53, 95% CI: 1.39–1.69, p < 0.00001), driven by CV death (RR: 1.88, 95% CI: 1.18–3.01, p = 0.008), MI (RR: 1.67, 95% CI: 1.21–2.31, p = 0.002) and ST (RR: 1.90, 95% CI: 1.27–2.84, p = 0.002). Patients with two CYP2C19 LoF alleles were correlated with significantly greater risk of MACE compared with noncarriers (RR: 3.91, 95% CI: 2.78–5.50, p < 0.00001). Further analysis revealed that the risk of MACE was markedly significant in Asian patients (RR: 2.02, 95% CI: 1.67–2.44, p < 0.00001) and was comparatively low significance in western patients (RR: 1.35, 95% CI: 1.20–1.52, p < 0.00001). There was no significantly different bleeding events in patients with CYP2C19 LoF alleles compared with noncarriers (RR: 0.99, 95% CI: 0.85–1.15, p = 0.87). The ACS patients inheriting CYP2C19 LoF alleles, who underwent PCI and were treated with clopidogrel were correlated with significantly increased risk of MACE compared with noncarriers.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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