Risk of major adverse cardiovascular events in CYP2C19LoF genotype guided clopidogrel against alternative antiplatelets for CAD patients undergoing PCI: Meta‐analysis

Mohitosh Biswas; Murshadul Alam Murad; Maliheh Ershadian; Most. Sumaiya Khatun Kali; Chonlaphat Sukasem

doi:10.1111/cts.70080

February 1, 2025Clinical and Translational ScienceOpen Access

Risk of major adverse cardiovascular events in CYP2C19LoF genotype guided clopidogrel against alternative antiplatelets for CAD patients undergoing PCI: Meta‐analysis

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Why the study?

Selection of rational P2Y12 receptor antagonists for CAD patients inheriting CYP2C19 LoF alleles remains conflicting.

Does clopidogrel increase major adverse cardiovascular events compared to alternative P2Y12 receptor antagonists in CAD patients with CYP2C19 LoF alleles undergoing PCI?

Structured PICO

Does clopidogrel increase major adverse cardiovascular events compared to alternative P2Y12 receptor antagonists in CAD patients with CYP2C19 LoF alleles undergoing PCI?

P

Population

Coronary artery disease (CAD) patients inheriting CYP2C19 loss-of-function (LoF) alleles undergoing percutaneous coronary intervention (PCI)

I

Intervention

Clopidogrel

C

Comparator

Alternative antagonists of P2Y12 receptor (prasugrel or ticagrelor)

O

Outcome

Major adverse cardiovascular events (MACE)composite

In CAD patients with CYP2C19 loss-of-function alleles undergoing PCI, clopidogrel is associated with a significantly higher risk of MACE compared to alternative P2Y12 inhibitors like prasugrel or ticagrelor, without a significant difference in bleeding.

Implication

Clopidogrel was associated with higher MACE risk in CYP2C19 LoF carriers post-PCI; leaves open whether routine genotyping improves outcomes in practice.

Abstract

Selection of rational antagonists of P2Y 12 receptor for CAD patients who inherit CYP2C19 LoF alleles remains still conflicting. This study compared the clinical outcomes in CAD patients inheriting CYP2C19 LoF alleles undergoing PCI and treated with clopidogrel against alternative antagonists of P2Y 12 receptor. A thorough literature search was performed across multiple scientific databases following the PRISMA guidelines and PICO model. Setting the statistical significance at p < 0.05 and RevMan software was used to calculate the risk ratios (RRs). Estimation of the pooled analysis revealed a significant 62% increased risk of major adverse cardiovascular events (MACE) in CAD patients inheriting CYP2C19 LoF alleles and treated with clopidogrel against those treated with alternative P2Y 12 receptor antagonists such as prasugrel or ticagrelor (RR 1.62; 95% CI 1.42–1.86; p < 0.00001). In addition, Asian CAD patients were found at a significantly higher risk of MACE (RR 1.93; 95% CI: 1.49–2.49; p < 0.00001) juxtaposed to CAD patients of other ethnicities (RR 1.51; 95% CI: 1.29–1.78; p < 0.00001). Conversely, between these two treatment groups, taking clopidogrel against prasugrel/ticagrelor, who possess CYP2C19 LoF alleles, no significant differences in bleeding events were observed (RR 0.94; 95% CI 0.79–1.11; p = 0.47). CAD patients undergoing PCI who inherited CYP2C19 LoF alleles and treated with clopidogrel were associated with significantly higher risk of MACE against those treated with alternative antagonists of P2Y 12 receptor, that is, prasugrel or ticagrelor.