Effect of Genotype Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

11-16-2021

Journal Title

Circulation

Department

Medicine

Abstract

Introduction: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite.

Hypothesis: The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment.

Methods: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints.

Results: Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE) (RR 0.72, 95% CI 0.55-0.95; p=0.02, I2=23), improved cardiovascular (CV) mortality (RR 0.62, 95% CI 0.43-0.90; p=0.01, I2=0) and reduced incidence of myocardial infarction (MI) (RR 0.57, 95% CI 0.41-0.97; p< 0.01), and a similar stroke incidence (RR 0.65, 95% CI 0.35-1.21; p= 0.18). Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm (RR 0.52, 95% CI 0.28-0.96; p=0.04).

Conclusions: Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

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