Abstract
Abstract
Background
Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency.
Methods
A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95–208 PRU), and bleeding risk (< 95 PRU).
Results
124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 − 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively.
Conclusion
ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.
Funder
This research was funded by Universitas Indonesia through the PUTI Grant
Publisher
Springer Science and Business Media LLC
Reference41 articles.
1. Kementerian Kesehatan RI, Hasil Utama RISKESDAS. 2018. 2018; http://www.depkes.go.id/resources/download/info-terkini/materi_rakorpop_2018/Hasil Riskesdas 2018.pdf.
2. Del Brutto VJ, Chaturvedi S, Diener H-C, Romano JG, Sacco RL. Antithrombotic Therapy to Prevent Recurrent Strokes in Ischemic Cerebrovascular Disease. J Am Coll Cardiol [Internet]. 2019;74(6):786–803. https://linkinghub.elsevier.com/retrieve/pii/S0735109719356967.
3. Rasyid A, Kurniawan M, Mesiano T, Hidayat R, Harris S. Stroke Iskemik. In: Aninditha T, Harris S, Wiratman W, editors. Buku ajar neurologi. 2nd editio. Jakarta: Departemen Neurologi FKUI-RSCM; 2022. pp. 167–75.
4. Kleindorfer DO, Towfighi A, Chaturvedi S, Cockroft KM, Gutierrez J, Lombardi-Hill D et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke [Internet]. 2021;52(7). https://www.ahajournals.org/doi/https://doi.org/10.1161/STR.0000000000000375.
5. Ackerson T, Adeoye OM, Brown M, Demaerschalk BM, Hoh B, Leslie-mazwi TM et al. AHA / ASA Guideline 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke. 2018.