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

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.

Guided Anti-P2Y12 Therapy in Patients Undergoing Percutaneous Coronary Intervention

“…In conclusion, both strategies of GT proved effective in China, likely due not only to the high prevalence of unfavorable gene mutations but also to the particularly high risk for MACE associated with them in populations of East/South Asia. 23,24 In the RoW, the dubious efficacy of genotype-GT reflects the marginal role played by gene mutations in the response to clopidogrel in these Countries. 25 The unquestionable failure of PFT-GT in the RoW to reduce MACE (RR=1.08) should be adequately emphasized, considering that PFT-GT is still implemented in many Centers in Western Countries, absorbing economic resources and increasing the workload of healthcareworkers.…”

“…In conclusion, both strategies of GT proved effective in China, likely due not only to the high prevalence of unfavorable gene mutations but also to the particularly high risk for MACE associated with them in populations of East/South Asia. 23,24 In the RoW, the dubious efficacy of genotype-GT Fig. 1 Differences between RCTs on HTPR-Therapy and RCTs on PFT-GT and potential influence on the results of real-world accuracy and ideal 100% accuracy of PFTs.…”

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies

“…The effects of CYP2C19 genetic variants on widely used antiplatelets, for example, clopidogrel in either CAD or stroke patients has been well-established including in Thai patients. The findings of these studies suggest that due to the high risk of major adverse cardiovascular events (MACE) such as death, recurrent MI, stroke, and stent thrombosis for patients carrying CYP2C19 loss-of-function (LoF) alleles, alternative antiplatelets such as prasugrel or ticagrelor not affected by the CYP2C19 genetic variants should be prescribed in order to reduce the risk of MACE (Sukasem et al, 2013;Biswas et al, 2020a;Biswas et al, 2022;Biswas and Kali, 2021b;Jafrin et al, 2021). The CPIC dosing guidelines already provided clinical recommendations for clopidogrel in acute coronary syndrome (ACS) patients with CYP2C19*2, *3, *17 variants (Scott et al, 2013).…”

Factors Associated with Platelet Activation-Recent Pharmaceutical Approaches

“…Compared to aspirin alone, DAPT may be efficacious in acute minor stroke or transient ischemic attacks [ 126 ], established cardiovascular disease [ 127 ], and in patients with diabetes mellitus [ 128 ], at the cost of increased bleeding rates. It should be noted, however, that in the presence of a CYP2C19 loss-of-function allele, patients treated with clopidogrel for stable coronary artery disease or after percutaneous revascularization for an acute coronary syndrome may be facing an increased risk of major adverse cardiovascular events [ 129 , 130 , 131 ]. P2Y 12 gene polymorphisms might also increase the incidence of atherosclerotic events in patients treated with clopidogrel [ 132 ].…”