Risk of major adverse cardiovascular events of CYP2C19 loss-of-function genotype guided prasugrel/ticagrelor vs clopidogrel therapy for acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Abstract

The most effective antiplatelet treatments for acute coronary syndrome (ACS) patients carrying CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI) is still debating and conflicting. It was aimed to compare the efficacy and safety endpoints for these patients treated with alternative P2Y12 receptor blockers (e.g. prasugrel or ticagrelor) against clopidogrel. Literature was searched in PubMed, Cochrane library, Synapse and 1000 Genomes databases following PRISMA guidelines for identifying relevant studies. Aggregated risk was estimated by RevMan software using either fixed/random-effects models where P values<0.05 (two-sided) were considered statistically significant. Nine studies comprising 16,132 ACS patients undergoing PCI were included in this analysis in which 2,746 and 2,640 patients were in the CYP2C19 LoF clopidogrel and alternatives treatment group, respectively. It was demonstrated that patients treated with prasugrel or ticagrelor significantly reduced the risk of MACEs (RR 0.58; 95% CI 0.45–0.76; P<0.0001) as compared to patients with clopidogrel where both groups carrying CYP2C19 LoF alleles. Subgroup analysis showed that prasugrel or ticagrelor significantly reduced the risk of cardiovascular death (RR 0.44; 95% CI: 0.25–0.74; P=0.002) and MI (RR 0.60; 95% CI: 0.44–0.81; P=0.0008) while other clinical outcomes were not found statistically significant between these two groups; stroke (RR 0.77; 95% CI: 0.43–1.38; P =0.39), stent thrombosis (RR 0.67; 95% CI: 0.38–1.18; P =0.17), unstable angina (RR 0.55; 95% CI: 0.13–2.33; P =0.42), revascularisation (RR 0.79; 95% CI: 0.28–2.24; P=0.66). Bleeding events were not found significantly different between these groups (RR 1.06; 95% CI: 0.88–1.28; P=0.55). Considering efficacy and safety, alternative antiplatelets (e.g. prasugrel or ticagrelor) may be regarded as better treatment option as compared to clopidogrel for ACS patients undergoing PCI.

Keywords:

• Acute coronary syndrome
• percutaneous coronary intervention
• antiplatelets
• CYP2C19 genetic polymorphisms
• efficacy and safety
• precision medicine

Authors Contribution

MB designed this study and performed all statistical analysis. Data extraction and analysis was double checked by MSKK and BI respectively. MB and MSKK was involved in selection process of included studies through Rayyan QCRI. MB drafted this article and BI and TKB reviewed critically for the improvement of overall quality and all authors were agreed to submit in this journal.

Disclosure Statement

The authors declared that there was no conflict of interest and no funding was available for this research. 

Data Availability

All raw and processed data used in this meta-analysis are available upon request.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

No funding was available for this research.