Impact of the CYP2C19*17 Allele on Outcomes in Patients Receiving Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
Aged
Clopidogrel
/ adverse effects
Coronary Artery Disease
/ diagnosis
Cytochrome P-450 CYP2C19
/ genetics
Female
Genotype
Hemorrhage
/ chemically induced
Humans
Male
Middle Aged
Percutaneous Coronary Intervention
/ adverse effects
Pharmacogenetics
Pharmacogenomic Testing
Pharmacogenomic Variants
Phenotype
Platelet Aggregation Inhibitors
/ adverse effects
Precision Medicine
Risk Assessment
Risk Factors
Thrombosis
/ etiology
Time Factors
Treatment Outcome
United States
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
09
06
2020
accepted:
18
08
2020
pubmed:
9
9
2020
medline:
16
7
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
Genotyping for CYP2C19 no function alleles to guide antiplatelet therapy after percutaneous coronary intervention (PCI) improves clinical outcomes. Although results for the increased function CYP2C19*17 allele are also reported, its clinical relevance in this setting remains unclear. A collaboration across nine sites examined antiplatelet therapy prescribing and clinical outcomes in 3,342 patients after implementation of CYP2C19-guided antiplatelet therapy. Risk of major atherothrombotic and bleeding events over 12 months after PCI were compared across cytochrome P450 2C19 isozyme (CYP2C19) metabolizer phenotype and antiplatelet therapy groups by proportional hazards regression. Clopidogrel was prescribed to a similar proportion of CYP2C19 normal (84.5%), rapid (82.9%), and ultrarapid metabolizers (80.6%) (P = 0.360). Clopidogrel-treated normal metabolizers (20.4 events/100 patient-years; adjusted hazard ratio (HR) 1.00, 95% confidence interval (CI), 0.75-1.33, P = 0.993) and clopidogrel-treated rapid or ultrarapid metabolizers (19.1 events/100 patient-years; adjusted HR 0.95, 95% CI, 0.69-1.30, P = 0.734) exhibited no difference in major atherothrombotic events compared with patients treated with prasugrel or ticagrelor (17.6 events/100 patient-years). In contrast, clopidogrel-treated intermediate and poor metabolizers exhibited significantly higher atherothrombotic event risk compared with prasugrel/ticagrelor-treated patients (adjusted HR 1.56, 95% CI, 1.12-2.16, P = 0.008). When comparing clopidogrel-treated rapid or ultrarapid metabolizers to normal metabolizers, no difference in atherothrombotic (adjusted HR 0.97, 95% CI, 0.73-1.29, P = 0.808) or bleeding events (adjusted HR 1.34, 95% CI, 0.83-2.17, P = 0.224) were observed. In a real-world setting of genotype-guided antiplatelet therapy, the CYP2C19*17 allele did not significantly impact post-PCI prescribing decisions or clinical outcomes. These results suggest the CYP2C19 *1/*17 and *17/*17 genotypes have limited clinical utility to guide antiplatelet therapy after PCI.
Identifiants
pubmed: 32897581
doi: 10.1002/cpt.2039
pmc: PMC7902344
mid: NIHMS1630735
doi:
Substances chimiques
Platelet Aggregation Inhibitors
0
Clopidogrel
A74586SNO7
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
705-715Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR003096
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000064
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002489
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL143161
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001427
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092173
Pays : United States
Organisme : NIMHD NIH HHS
ID : U54 MD010723
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010245
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG008958
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007762
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007269
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL105198
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001111
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL141690
Pays : United States
Organisme : NIGMS NIH HHS
ID : U01 GM074492
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000165
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL133373
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007775
Pays : United States
Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
J Mol Diagn. 2018 May;20(3):269-276
pubmed: 29474986
Clin Pharmacol Ther. 2006 Jan;79(1):103-13
pubmed: 16413245
Pharmacogenomics. 2014 May;15(7):915-23
pubmed: 24956245
Circulation. 2010 Feb 2;121(4):512-8
pubmed: 20083681
Clin Pharmacol Ther. 2012 May;91(5):774-6
pubmed: 22513313
Circ Genom Precis Med. 2018 Apr;11(4):e002069
pubmed: 29615454
Clin Pharmacol Ther. 2018 Oct;104(4):664-674
pubmed: 29280137
Eur J Clin Pharmacol. 2017 Dec;73(12):1623-1632
pubmed: 28914344
Genet Med. 2020 Jan;22(1):160-169
pubmed: 31316169
N Engl J Med. 2007 Nov 15;357(20):2001-15
pubmed: 17982182
Circ Cardiovasc Genet. 2013 Oct;6(5):514-21
pubmed: 24019397
Clin Pharmacol Ther. 2019 Mar;105(3):661-671
pubmed: 29536505
JACC Cardiovasc Interv. 2018 Jan 22;11(2):181-191
pubmed: 29102571
Genet Med. 2017 Feb;19(2):215-223
pubmed: 27441996
Clin Transl Sci. 2017 May;10(3):143-146
pubmed: 28294551
Clin Pharmacol Ther. 2013 Sep;94(3):317-23
pubmed: 23698643
N Engl J Med. 2009 Sep 10;361(11):1045-57
pubmed: 19717846
Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):647-652
pubmed: 30760018
JAMA. 2016 Sep 20;316(11):1205-1206
pubmed: 27654606
N Engl J Med. 2019 Oct 24;381(17):1621-1631
pubmed: 31479209
Clin Pharmacol Ther. 2017 Sep;102(3):493-501
pubmed: 28124392
J Am Coll Cardiol. 2018 May 1;71(17):1869-1877
pubmed: 29540324
Circulation. 2009 May 19;119(19):2553-60
pubmed: 19414633
J Thromb Haemost. 2010 Aug;8(8):1685-93
pubmed: 20492469
Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):76-84
pubmed: 24616408
Lancet. 2010 Oct 16;376(9749):1320-8
pubmed: 20801498
Circulation. 2020 Mar 3;141(9):e139-e596
pubmed: 31992061
Expert Rev Clin Pharmacol. 2018 Feb;11(2):151-164
pubmed: 28689434
Circ Genom Precis Med. 2020 Feb;13(1):e002640
pubmed: 31928229
JACC Cardiovasc Interv. 2019 Aug 26;12(16):1521-1537
pubmed: 31202949
Lancet. 2017 Oct 14;390(10104):1747-1757
pubmed: 28855078
J Thromb Haemost. 2013 Sep;11(9):1640-6
pubmed: 23809542
Circ Cardiovasc Interv. 2019 Apr;12(4):e007811
pubmed: 30998396
JAMA Intern Med. 2018 Jul 1;178(7):943-950
pubmed: 29799992
Expert Opin Drug Metab Toxicol. 2018 Apr;14(4):447-460
pubmed: 29620484
JAMA. 2010 Oct 27;304(16):1821-30
pubmed: 20978260
Thromb Haemost. 2018 Sep;118(9):1656-1667
pubmed: 30103241
J Transl Med. 2018 Apr 11;16(1):92
pubmed: 29642909
Am Heart J. 2010 Sep;160(3):506-12
pubmed: 20826260
J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2915-2931
pubmed: 30522654
Clin Pharmacol Ther. 2017 Jul;102(1):45-51
pubmed: 27981572
Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):56-67
pubmed: 24616371
Clin Pharmacol Ther. 2016 Jul;100(1):67-74
pubmed: 26693963
Circulation. 2011 Jun 14;123(23):2736-47
pubmed: 21670242
Clin Pharmacol Ther. 2017 Sep;102(3):502-510
pubmed: 28090649
Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(4):203-210
pubmed: 31504375