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Original Research

The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome

ORCID Icon, ORCID Icon, , , , , & ORCID Icon show all
Pages 287-295 | Published online: 21 Oct 2019
 

Abstract

Aims

The present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.

Methods

We screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females.

Results

The median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06).

Conclusion

The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.

Acknowledgments

The authors are grateful to Dr T Van Der Straaten for critically reviewing earlier versions of the manuscript. An abstract of this paper with interim findings was accepted as a poster presentation at the ESC Conference, 2019; FP Number: P6412.

Disclosure

Dr Zan Mitrev is the hospital director at the Zan Mitrev Clinic. The authors report no other conflicts of interest in this work.

Additional information

Funding

Internal funds supported this work: the costs for the assays and subsequent analyses were covered by using Zan Mitrev Clinic research funds.