Genotyping-guided approach versus the conventional approach in selection of oral P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome

Abstract

Objective The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS). Methods This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards. Results Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction. Conclusions In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR. Clinical Trial Registration URL: https://ichgcp.net/clinical-trials-registry/NCT01994941" title="See in ClinicalTrials.gov">NCT01994941.

Keywords: CYP2C19; P2Y12 receptor; acute coronary syndrome.

Figures

Figure 1.

Study design. Patients were provided loading doses of clopidogrel and then randomized into the genotyping-guided treatment group or the standard treatment group. Patients in the genotyping-guided treatment group were genotyped with the Verigene system and those with CYP2C19 LoF allele were switched to ticagrelor. All of the patients in the standard treatment group continued on clopidogrel. Platelet reactivity was assessed at 24 hours after the first loading dose of clopidogrel and 1 month afterwards.

Figure 2.

Study patients.

Figure 3.

On-treatment platelet reactivity at 24 hours and 1 month. The red line denotes patients with clinical events. Patient 1 suffered from subarachnoid haemorrhage. Patient 2 suffered from recurrent NSTEMI and acute upper gastrointestinal bleeding, which required intervention. Patient 3 had recurrent NSTEMI and patient 4 suffered from acute ischemic stroke.