Association among PlA1/A2 gene polymorphism, laboratory aspirin resistance and clinical outcomes in patients with coronary artery disease: An updated meta-analysis

Fei Wang,Jianling Bai,Jing Wang,Jie Liu,Deyu Kong,Chunjian Li,Ke Xu,Jun Chen,Haoyu Meng,Xiaoxuan Gong,Yaqing Zhou

doi:10.1038/s41598-019-49123-y

Abstract

The aim of this study was to investigate the association among the PlA1/A2 gene polymorphism, laboratory aspirin resistance and adverse clinical outcomes in coronary artery disease (CAD) patients who were on aspirin maintainance therapy. A comprehensive literature search was performed and 35 eligible clinical trials including 19025 CAD patients were recruited. Adverse clinical outcomes involving all-cause death, non-fatal myocardial infarction (MI), ischemic stroke and target vessel revascularization (TVR) were analyzed. The definition of aspirin resistance in each study was accepted. Meta-analysis was performed using the Review Manager 5.3.5 System. In CAD patients, the PlA2 gene carriers had similar incidence of laboratory aspirin resistance compared to those with PlA1/A1 genotype [29.7% vs 28.3%, OR = 0.94 (95% CI 0.63 to 1.40, P = 0.74)], and there were no significant differences in the adverse clinical outcomes between the PlA2 carriers and the PlA1/A1 genotype patients. However, the laboratory aspirin non-responders had higher risks of death [7.9% vs. 2.5%, OR = 2.42 (95% CI 1.86 to 3.15, P < 0.00001)] and TVR [4.5% vs. 1.7%, OR = 2.20 (95% CI 1.19 to 4.08, P = 0.01)] compared to the responders. In aspirin-treated CAD patients, the laboratory aspirin resistance predicts all-cause death and TVR. However, the PlA1/A2 gene polymorphism predicts neither the laboratory aspirin response nor the clinical outcomes.

Highlights

IntroductionAspirin (acetylsalicylic acid) is a well-known baseline anti-platelet agent for the treatment and prevention of coronary artery disease (CAD)
Aspirin is a well-known baseline anti-platelet agent for the treatment and prevention of coronary artery disease (CAD)
In this systematic review and meta-analysis we have found that: (1) there is no significant association between the PlA1/A2 polymorphism and aspirin resistance, or the PlA1/A2 polymorphism and worse clinical outcomes

Summary

Introduction

Aspirin (acetylsalicylic acid) is a well-known baseline anti-platelet agent for the treatment and prevention of coronary artery disease (CAD). It irreversibly acetylates a serine residue at position 529 in platelet prostaglandin synthase, and inhibits cyclooxygenase (COX) channel associated with platelet aggregation. PlA1/A2 polymorphism, a single nucleotide substitution (T → C) at position 1565 in exon 2 of the GP IIIa (a component of the final platelet aggregation pathway GPIIb/IIIa) gene has been reported to be associated with the laboratory detected aspirin resistance[2,3,4,5] and adverse clinical outcomes[6,7,8,9]. Study results regarding whether aspirin resistance is associated with adverse cardiovascular events are inconsistent[13,14,15,16,17]. Source Abderrazek F et al, 2010 Beiyun W et al, 2014 Bernardo E et al, 2006 Chunxiao L, et al, 2011 Fei G et al, 2011 Kranzhofer R et al, 2006 Lev EI et al, 2007 Macchi L et al, 2003 Pamukcu B et al, 2005 Papp E et al, 2005 Zanxin W et al, 2013 Godeneche et al, 2009 Jefferson et al, 2005 Kunicki et al, 2009 Lordkipanidze et al, 2011 Pamukucu et al, 2010

Objectives

Methods

Results

Conclusion