CYP2C19 loss-of-function alleles and use of omeprazole or esomeprazole increase the risk of cardiovascular outcomes in patients using clopidogrel.
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
27
07
2023
received:
12
06
2023
accepted:
28
07
2023
medline:
23
10
2023
pubmed:
8
8
2023
entrez:
8
8
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37551775
doi: 10.1111/cts.13608
pmc: PMC10582682
doi:
Substances chimiques
Clopidogrel
A74586SNO7
Platelet Aggregation Inhibitors
0
Esomeprazole
N3PA6559FT
Omeprazole
KG60484QX9
Cytochrome P-450 CYP2C19
EC 1.14.14.1
CYP2C19 protein, human
EC 1.14.14.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2010-2020Informations de copyright
© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
Références
N Engl J Med. 2019 Oct 24;381(17):1621-1631
pubmed: 31479209
J Geriatr Cardiol. 2016 Mar;13(3):209-17
pubmed: 27103915
Br J Clin Pharmacol. 2015 Feb;79(2):222-40
pubmed: 24913012
N Engl J Med. 2007 Nov 15;357(20):2001-15
pubmed: 17982182
N Engl J Med. 2021 Dec 30;385(27):2520-2530
pubmed: 34708996
J Pharmacol Exp Ther. 2015 Sep;354(3):426-30
pubmed: 26159874
J Cardiovasc Pharmacol Ther. 2017 Mar;22(2):142-152
pubmed: 27512080
Kardiol Pol. 2018;76(2):229-313
pubmed: 29457615
Lancet. 2009 Sep 19;374(9694):989-997
pubmed: 19726078
J Am Heart Assoc. 2017 Feb 14;6(2):
pubmed: 28196815
Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(4):203-210
pubmed: 31504375
Am Heart J. 2016 Jul;177:1-8
pubmed: 27297843
Clin Pharmacol Ther. 2018 Feb;103(2):281-286
pubmed: 28653333
Aliment Pharmacol Ther. 2010 Apr;31(8):810-23
pubmed: 20102352
Drug Metab Dispos. 2004 Aug;32(8):821-7
pubmed: 15258107
Circulation. 2006 Nov 28;114(22):e600-6
pubmed: 17130347
JACC Cardiovasc Interv. 2018 Jan 22;11(2):181-191
pubmed: 29102571
N Engl J Med. 2009 Jan 22;360(4):363-75
pubmed: 19106083
Dig Dis Sci. 2010 Jul;55(7):1964-8
pubmed: 19731021
Acta Cardiol Sin. 2019 Jul;35(4):402-411
pubmed: 31371901
Clin Pharmacol Ther. 2011 Jan;89(1):65-74
pubmed: 20844485
N Engl J Med. 2009 Sep 10;361(11):1045-57
pubmed: 19717846
Thromb Res. 2014 Apr;133(4):599-605
pubmed: 24440142
Circulation. 2012 Feb 28;125(8):978-86
pubmed: 22261200
Pulm Pharmacol Ther. 2014 Apr;27(2):129-38
pubmed: 24468677
Circulation. 2011 Feb 8;123(5):474-82
pubmed: 21262992
Arch Intern Med. 2010 Apr 26;170(8):704-10
pubmed: 20421557
Clin Pharmacol Ther. 2021 Feb;109(2):352-366
pubmed: 32602114
N Engl J Med. 2010 Nov 11;363(20):1909-17
pubmed: 20925534
Stroke Vasc Neurol. 2021 Jun;6(2):280-285
pubmed: 33952670
Int J Epidemiol. 2012 Oct;41(5):1265-71
pubmed: 21642350
Clin Pharmacol Ther. 2022 Nov;112(5):959-967
pubmed: 35034351
Int J Clin Pharm. 2021 Oct;43(5):1360-1369
pubmed: 33774763
Am J Manag Care. 2010 Feb;16(2):116-22
pubmed: 20148616
J Am Coll Cardiol. 2018 May 1;71(17):1869-1877
pubmed: 29540324
Pharmacotherapy. 2010 Aug;30(8):787-96
pubmed: 20653354
Circulation. 2006 Feb 21;113(7):e166-286
pubmed: 16490830
N Engl J Med. 2010 Oct 28;363(18):1704-14
pubmed: 20979470
JAMA. 2010 Oct 27;304(16):1821-30
pubmed: 20978260
Eur J Epidemiol. 1997 Feb;13(2):133-8
pubmed: 9084994
Pharmacogenomics J. 2015 Feb;15(1):20-5
pubmed: 25001880
Clin Transl Sci. 2023 Oct;16(10):2010-2020
pubmed: 37551775