Ticagrelor is more effective than clopidogrel in carrier of nonfunctional <i>CYP2C19</i> allele who has diabetes and acute coronary syndrome - case report and literature review

Rahel Tekeste; Gregorio Garza; Song Han; Jianli Dong; Rahel Tekeste; Gregorio Garza; Song Han; Jianli Dong

doi:10.3934/molsci.2022004

AIMS Molecular Science

2022, Volume 9, Issue 2: 66-78. doi: 10.3934/molsci.2022004

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Case report

Ticagrelor is more effective than clopidogrel in carrier of nonfunctional CYP2C19 allele who has diabetes and acute coronary syndrome - case report and literature review

1.
School of Medicine, University of Texas Medical Branch, Galveston, TX, USA
2.
Health Sciences Division, University of Monterrey, Monterrey, NL, Mexico
3.
Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

Received: 12 January 2022 Revised: 15 April 2022 Accepted: 23 April 2022 Published: 28 April 2022

Clopidogrel is a purinergic receptor P2Y12 (P2RY12)-blocking pro-drug used to inhibit platelet aggregation in patients at risk for major adverse cardiac events (MACE), such as coronary artery disease and stroke. Despite clopidogrel therapy, some patients may still present with recurrent cardiovascular events. One possible cause of recurrence are variants in the cytochrome P450 2C19 (CYP2C19) gene. CYP2C19 is responsible for the metabolism of many drugs including clopidogrel. Recent studies have associated pharmacogenetics testing of CYP2C19 variants to guide clopidogrel therapy with a decreased risk of certain recurrent MACEs. Through a different mechanism, diabetes mellitus (DM) and obesity are also associated with clopidogrel treatment failure. We describe the case of a 64-year-old Caucasian woman with a history of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI), and DM/obesity, who presented to University of Texas Medical Branch (UTMB) in 2019 with a transient ischemic attack (TIA) while on clopidogrel/aspirin dual anti-platelet therapy. After CYP2C19 genetic testing revealed that she was an intermediate metabolizer with a heterozygous *2 genotype, ticagrelor replaced the clopidogrel treatment regimen. No future MACEs were documented in the two-year patient follow-up. Thus, ACS patients with DM/obesity who have undergone PCI and are intermediate CYP2C19 metabolizers may yield better treatment outcomes if prescribed ticagrelor instead of clopidogrel. Whether this improvement was due to genotype-guided therapy or the differing interactions of clopidogrel/ticagrelor in DM/obese patients is unknown based on available data. Regardless, CYP2C19 genotype-guided treatment of ACS/PCI patients, with consideration of DM/obesity status, may provide effective individualized therapy compared to standard treatment. The inclusion of DM/obesity in this study is clinically relevant because DM/obesity has become a major health issue in the United States and worldwide.
- CYP2C19,
- clopidogrel,
- P2RY12,
- pharmacogenetics,
- intermediate CYP2C19 metabolizer,
- MACE,
- ACS,
- PCI
Citation: Rahel Tekeste, Gregorio Garza, Song Han, Jianli Dong. Ticagrelor is more effective than clopidogrel in carrier of nonfunctional CYP2C19 allele who has diabetes and acute coronary syndrome - case report and literature review[J]. AIMS Molecular Science, 2022, 9(2): 66-78. doi: 10.3934/molsci.2022004

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Abstract

Clopidogrel is a purinergic receptor P2Y12 (P2RY12)-blocking pro-drug used to inhibit platelet aggregation in patients at risk for major adverse cardiac events (MACE), such as coronary artery disease and stroke. Despite clopidogrel therapy, some patients may still present with recurrent cardiovascular events. One possible cause of recurrence are variants in the cytochrome P450 2C19 (CYP2C19) gene. CYP2C19 is responsible for the metabolism of many drugs including clopidogrel. Recent studies have associated pharmacogenetics testing of CYP2C19 variants to guide clopidogrel therapy with a decreased risk of certain recurrent MACEs. Through a different mechanism, diabetes mellitus (DM) and obesity are also associated with clopidogrel treatment failure. We describe the case of a 64-year-old Caucasian woman with a history of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI), and DM/obesity, who presented to University of Texas Medical Branch (UTMB) in 2019 with a transient ischemic attack (TIA) while on clopidogrel/aspirin dual anti-platelet therapy. After CYP2C19 genetic testing revealed that she was an intermediate metabolizer with a heterozygous *2 genotype, ticagrelor replaced the clopidogrel treatment regimen. No future MACEs were documented in the two-year patient follow-up. Thus, ACS patients with DM/obesity who have undergone PCI and are intermediate CYP2C19 metabolizers may yield better treatment outcomes if prescribed ticagrelor instead of clopidogrel. Whether this improvement was due to genotype-guided therapy or the differing interactions of clopidogrel/ticagrelor in DM/obese patients is unknown based on available data. Regardless, CYP2C19 genotype-guided treatment of ACS/PCI patients, with consideration of DM/obesity status, may provide effective individualized therapy compared to standard treatment. The inclusion of DM/obesity in this study is clinically relevant because DM/obesity has become a major health issue in the United States and worldwide.

Acknowledgments

This work was supported in part by the National Institutes of Health (NIH) fund (TL1TR001440), for which RT is a predoctoral trainee. This study was approved by the UTMB's Institutional Review Board (IRB # 02-089).

Conflict of Interest

All authors declare no conflict of interest in this paper.

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