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

Authors Kapedanovska-Nestorovska A, Dimovski AJ, Sterjev Z, Matevska Geskovska N, Suturkova L, Ugurov P, Mitrev Z, Rosalia R

Received 12 July 2019

Accepted for publication 23 September 2019

Published 21 October 2019 Volume 2019:12 Pages 287—295


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth

Aleksandra Kapedanovska-Nestorovska,1 Aleksandar J Dimovski,1,2 Zoran Sterjev,1 Nadica Matevska Geskovska,1 Ljubica Suturkova,1 Petar Ugurov,3 Zan Mitrev,4 Rodney Rosalia5

1Center for Biomolecular and Pharmaceutical Analysis, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje, Republic of North Macedonia; 2Research Center for Genetic Engineering and Biotechnology “Georgi D.Efremov”, Macedonian Academy of Sciences and Arts, Skopje, Republic of North Macedonia; 3Semi Intensive Care Unit, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 4Department of Cardiovascular Surgery, Zan Mitrev Clinic, Skopje, Republic of North Macedonia; 5Department of Clinical Research, Zan Mitrev Clinic, Skopje, Republic of North Macedonia

Correspondence: Rodney Rosalia
Zan Mitrev Clinic, Bledski Dogovor #8, Skopje 1000, Republic of Macedonia
Tel +389 71305957

Aleksandra Kapedanovska-Nestorovska
Faculty of Pharmacy, University Ss Cyril and Methodius, Mother Theresa 47, Skopje 1000, Republic of Macedonia
Tel +389 72228998

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.

Keywords: AKR1D1, CYP2C19, MACCE, DAPT, clopidogrel, North Macedonia

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