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. 2025 May 12:12:1572389.
doi: 10.3389/fcvm.2025.1572389. eCollection 2025.

Genetic and clinical determinants of MACE and haemorrhage in antiplatelet therapy: insights from pharmacogenomic analysis

Yubo Wang  1   2 , Shuangli Yuan  3 , Muyun Li  4 , Wenling Feng  1   2 , Jing Li  1   2 , Wenwen Chen  1   2 , Aliye Berdi  4 , Yulian Kou  4 , Yuan Yuan  1   2 , Jun Zhao  1   2
Affiliations

Genetic and clinical determinants of MACE and haemorrhage in antiplatelet therapy: insights from pharmacogenomic analysis

Yubo Wang et al. Front Cardiovasc Med. .

Abstract

Background: Variability in responses to clopidogrel and aspirin therapy for coronary artery disease has driven interest in pharmacogenomics. This study investigates the role of genetic variants in CYP2C19, ABCB1, and PON1 in predicting adverse cardiovascular events and guiding personalised antiplatelet therapy.

Methods: A retrospective cohort study designed to compare the effectiveness and safety of the risk levels from CYP2C19 (*2, *3, *17), ABCB1 C3435T, and PON1 Q192R polymorphisms. The primary outcome was the incidence of haemorrhage and major adverse cardiovascular events (MACE). Kaplan Merir curves and Cox regression with IPTW adjustments were used for analysis.

Results: The results of this study indicate that patients in Group A, who received treatment consistent with multigene testing (CYP2C19, ABCB1, and PON1), experienced significantly lower major adverse cardiovascular events (MACE) compared to Group B. Multigene testing proved to be more accurate in predicting clopidogrel effectiveness and reducing adverse events without an increased risk of haemorrhage (HR 0.671, 95% CI: 0.526-0.855, P = 0.001). Patients in Group A showed no significant difference in haemorrhage risk compared to Group B, with an HR of 0.831 (95% CI: 0.598-1.155, P = 0.271) after adjustment.

Conclusion: Multigene-guided antiplatelet therapy is more effective in reducing adverse cardiovascular events. Further prospective studies are needed to validate these findings, incorporating genetic, environmental, and lifestyle factors for a comprehensive personalised medicine approach.

Keywords: antiplatelet therapy; cardiovascular events; clopidogrel; multigene testing; personalized medicine; pharmacogenomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Standardized mean difference for the covariates before and after weighting. BMI, body mass index; EF, left ventricular ejection fraction; IPTW, Inverse probability of treatment weight.
Figure 2
Figure 2
Probabilities of MACE and haemorrhagic event with the 60 months follow-up. (a): MACE event probabilities during 60 months follow-up before IPTW; (b) MACE event probabilities during 60 months follow-up after IPTW; (c): Haemorrhagic event probabilities during 60 months follow-up before IPTW; (d): Haemorrhagic event probabilities during 60 months follow-up after IPTW.
Figure 3
Figure 3
Nomogram for predicting 1-year, 3-year, and 5-year MACE probability in patients undergoing antiplatelet therapy before IPTW.
Figure 4
Figure 4
Nomogram for predicting 1-year, 3-year, and 5-year haemorrhage probability in patients undergoing antiplatelet therapy after IPTW.
See this image and copyright information in PMC

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