Platelet Function and Genotype after DES Implantation in East Asian Patients: Rationale and Characteristics of the PTRG-DES Consortium

Abstract

Purpose: Platelet function test (PFT) results and genotype hold unique prognostic implications in East Asian patients. The aim of the PTRG-DES (Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease) consortium is to assess the clinical impact thereof on long-term clinical outcomes in Korean patients with coronary artery disease during dual antiplatelet therapy (DAPT) including clopidogrel.

Materials and methods: Searching publications on the PubMed, we reviewed clopidogrel treatment studies with PFT and/or genotype data for potential inclusion in this study. Lead investigators were invited to share PFT/genotype results, patient characteristics, and clinical outcomes to evaluate relationships among them.

Results: Nine registries from 32 academic centers participated in the PTRG-DES consortium, contributing individual patient data from 13160 patients who underwent DES implantation between July 2003 and August 2018. The PTRG-PFT cohort was composed of 11714 patients with available VerifyNow assay results. Platelet reactivity levels reached 218±79 P2Y12 reaction units (PRU), and high on-clopidogrel platelet reactivity based on a consensus-recommended cutoff (PRU >208) was observed in 55.9%. The PTRG-Genotype cohort consisted of 8163 patients with candidate genotypes related with clopidogrel responsiveness. Of those with cytochrome P450 (CYP) 2C19 genotype, frequencies of carrying one and two loss-of-function allele (s) (^*2 or ^*3) were 47.9% (intermediate metabolizers) and 14.2% (poor metabolizers), respectively.

Conclusion: The PTRG-DES consortium highlights unique values for on-clopidogrel platelet reactivity and CYP2C19 phenotype that may be important to developing optimal antiplatelet regimens in East Asian patients.

Trial registration: ClinicalTrials.gov Identifier: NCT04734028.

Keywords: East Asia; coronary artery disease; drug-eluting stent; genotype; platelet function.

Fig. 1. Cohorts of the PTRG-DES consortium. ABCB1, ATP Binding Cassette Subfamily B Member 1; CYP, cytochrome P450; PFT, platelet function test; PON1, Paraoxonase 1; PTRG-DES, Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated patients with coronary artery disease.

Fig. 2. Kaplan-Meier analysis for MACCE and major bleeding events (PTRG-DES consortium; n=13160). The blue line represents cumulative event rates of MACCE and the red line represents cumulative event rates of major bleeding events during follow-up period in this consortium. MACCE, major adverse cardiac and cerebrovascular events; PTRG-DES, Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease.

Fig. 3. PRU and ARU levels in patients with (red) vs. without (blue) ischemic events (MACCE). PRU, P2Y12 reaction unit; ARU, aspirin reaction unit; MACCE, major adverse cardiac and cerebrovascular events.

Fig. 4. Kaplan-Meier analysis for the association between HPR and MACCE and major bleeding events. (A) HPR to ADP (PRU >208) and MACCE and major bleeding events. (B) HPR to arachidonic acid (ARU >550) and MACCE and major bleeding events. HPR, high platelet reactivity; MACCE, major adverse cardiac and cerebrovascular events; ADP, adenosine diphosphate; PRU, P2Y12 reaction units; ARU, aspirin reaction units.

Fig. 5. Kaplan-Meier analysis for the association between CYP2C19 phenotype and MACCE. MACCE, major adverse cardiac and cerebrovascular events; EM, extensive metabolizers; IM, intermediate metabolizers; PM, poor metabolizers.