CYP2C19 loss‐of‐function alleles and use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel
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| Název: | CYP2C19 loss‐of‐function alleles and use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel |
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| Autoři: | Kiiski Johanna I., Sinisalo Juha, Ramste Markus, Ritvos Markus, Niemi Mikko |
| Přispěvatelé: | Clinicum, HUS Heart and Lung Center, INDIVIDRUG - Individualized Drug Therapy, Research Programs Unit, Department of Clinical Pharmacology, HUSLAB, Medicum, HUS Diagnostic Center, Department of Medicine, HUS Physiology, Genetics and Preanalytics |
| Zdroj: | Clin Transl Sci Clinical and Translational Science, Vol 16, Iss 10, Pp 2010-2020 (2023) |
| Informace o vydavateli: | Wiley, 2023. |
| Rok vydání: | 2023 |
| Témata: | Ticagrelor, Platelet inhibition, Genotype, Proton pump inhibitors, Events, RM1-950, Association, Humans, Prospective Studies, Clinical-outcomes, Pantoprazole, Alleles, Research, Esomeprazole, General medicine, internal medicine and other clinical medicine, 3. Good health, Phenoconversion, Clopidogrel, Cytochrome P-450 CYP2C19, Stroke, Impact, Treatment Outcome, Therapeutics. Pharmacology, Public aspects of medicine, RA1-1270, Platelet Aggregation Inhibitors, Omeprazole |
| Popis: | Our aim was to investigate in a real‐life prospective patient cohort how CYP2C19 loss‐of‐function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants. The primary study outcome measurement was cardiovascular death or recurring myocardial infarction or stroke. Altogether, 608 patients (30.8%) carried CYP2C19 LOF alleles. During the 365‐day follow‐up 252 patients (12.8%) had an ischemic vascular event. Cardiovascular events were significantly more frequent in carriers of CYP2C19 LOF alleles (14.8%, 95% confidence interval [CI], 11.7–17.8) than in non‐carriers (10.8%, 95% CI, 9.0–12.6, p = 0.0159). Omeprazole or esomeprazole use was similar among LOF allele carriers (n = 131, 21.5%) and non‐carriers (n = 250, 18.3%, p = 0.185). Cardiovascular events were significantly more common in a composite group consisting of all CYP2C19 LOF carriers regardless of proton pump inhibitor use status and non‐carriers using omeprazole or esomeprazole than in non‐carriers not using omeprazole or esomeprazole (14.8%, 95% CI, 12.2–17.3 vs. 9.9%, 95% CI, 8.0–11.9, p = 0.00173). We observed significantly more cardiovascular events in carriers of CYP2C19 LOF variants and in non‐carriers using omeprazole or esomeprazole. For optimal patient care, both genetics and concomitant medication should be considered. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1752-8062 1752-8054 |
| DOI: | 10.1111/cts.13608 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/37551775 https://doaj.org/article/ebb5f4676e22413aad2e3b7c6e59dfd7 http://hdl.handle.net/10138/567752 |
| Rights: | CC BY NC ND URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Přístupové číslo: | edsair.doi.dedup.....d8fcd15c9bdfd7d908dd792f23eb7f0a |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Our aim was to investigate in a real‐life prospective patient cohort how CYP2C19 loss‐of‐function (LOF) variants and CYP2C19 inhibitor omeprazole or esomeprazole influence the incidence of cardiovascular events in patients using clopidogrel. Data based simultaneously on these factors are conflicting and sparse. A cohort of prospective patients (n = 1972) with acute coronary syndrome (n = 1302) or symptomatic chronic coronary disease (n = 656) was followed for 365 days after hospitalization with information on purchased prescription drugs, hospital discharge, death, and genotype for CYP2C19*2, CYP2C19*3, and CYP2C19*8 LOF variants. The primary study outcome measurement was cardiovascular death or recurring myocardial infarction or stroke. Altogether, 608 patients (30.8%) carried CYP2C19 LOF alleles. During the 365‐day follow‐up 252 patients (12.8%) had an ischemic vascular event. Cardiovascular events were significantly more frequent in carriers of CYP2C19 LOF alleles (14.8%, 95% confidence interval [CI], 11.7–17.8) than in non‐carriers (10.8%, 95% CI, 9.0–12.6, p = 0.0159). Omeprazole or esomeprazole use was similar among LOF allele carriers (n = 131, 21.5%) and non‐carriers (n = 250, 18.3%, p = 0.185). Cardiovascular events were significantly more common in a composite group consisting of all CYP2C19 LOF carriers regardless of proton pump inhibitor use status and non‐carriers using omeprazole or esomeprazole than in non‐carriers not using omeprazole or esomeprazole (14.8%, 95% CI, 12.2–17.3 vs. 9.9%, 95% CI, 8.0–11.9, p = 0.00173). We observed significantly more cardiovascular events in carriers of CYP2C19 LOF variants and in non‐carriers using omeprazole or esomeprazole. For optimal patient care, both genetics and concomitant medication should be considered. |
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| ISSN: | 17528062 17528054 |
| DOI: | 10.1111/cts.13608 |