Impact of CYP2C19 Genotype on Efficacy and Safety of Clopidogrel-based Antiplatelet Therapy in Stroke or Transient Ischemic Attack Patients: An Updated Systematic Review and Meta-analysis of Non-East Asian Studies.
CYP2C19
Clopidogrel
Ischemic Stroke
Transient Ischemic Attack
meta-analysis
Journal
Cardiovascular drugs and therapy
ISSN: 1573-7241
Titre abrégé: Cardiovasc Drugs Ther
Pays: United States
ID NLM: 8712220
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
accepted:
23
11
2023
medline:
1
12
2023
pubmed:
1
12
2023
entrez:
1
12
2023
Statut:
aheadofprint
Résumé
Inconclusive and limited results have been reported on the clinical utility of CYP2C19 genotyping in stroke/TIA patients of non-East Asian ancestries. We herein performed an updated systematic review and meta-analysis to quantitatively estimate the association of CYP2C19 loss-of function (LOF) status with efficacy and safety of clopidogrel-based antiplatelet therapy in non-East Asian patients affected by stroke or TIA. A comprehensive search was performed up to July 2023 using PubMed, Web of Knowledge, and Cochrane Library databases. The clinical outcomes investigated were stroke, composite vascular events and bleeding. Pooled estimates were calculated as risk ratios (RR) with 95% CI using the Mantel- Haenszel random-effects model. The quality of evidence was assessed using the GRADEpro tool. A total number of 1673 stroke/TIA patients from 8 non-East Asian studies, published between 2014 and 2022, were included in the systematic review. Clopidogrel-treated carriers of CYP2C19 LOF alleles were found at increased risk of stroke compared to non-carriers (RR: 1.68, 95%CI: 1.04-2.71, P = 0.03). However, no significant association was observed with the risk of composite vascular events (RR: 1.15, 95%CI: 0.58-2.28, P = 0.69) or bleeding (RR: 0.84, 95%CI: 0.38-1.86, P = 0.67). Similarly, European ancestry patients carrying CYP2C19 LOF alleles displayed a higher risk of stroke (RR: 2.69 (1.11-6.51, P = 0.03), but not of composite vascular events or bleeding. The present updated meta-analysis provides moderate quality evidence of association between CYP2C19 LOF alleles and an increased risk of stroke in non-East Asian patients with stroke/TIA after receiving clopidogrel therapy. Further large pharmacogenetic studies are still warranted to corroborate these findings.
Identifiants
pubmed: 38038819
doi: 10.1007/s10557-023-07534-0
pii: 10.1007/s10557-023-07534-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
Références
GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021; 20:795–820.
Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization (WSO): global Stroke fact sheet 2022. Int J Stroke. 2022;17:18–29.
doi: 10.1177/17474930211065917
pubmed: 34986727
Donkor ES. Stroke in the 21st Century: a snapshot of the Burden, Epidemiology, and Quality of Life. Stroke Res Treat. 2018;3238165.
Easton JD, Saver JL, Albers GW, healthcare professionals from the American Heart Association/American Stroke Association Stroke Council. Definition and evaluation of transient ischemic attack: a scientific statement for ; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009; 40:2276–93.
Rothwell PM, Warlow CP. Timing of TIAs preceding Stroke: time window for prevention is very short. Neurology. 2005;64:817–20.
doi: 10.1212/01.WNL.0000152985.32732.EE
pubmed: 15753415
Kleindorfer DO, Towfighi A, Chaturvedi S, 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. 2021;52:e364–e467.
doi: 10.1161/STR.0000000000000375
pubmed: 34024117
Dawson J, Béjot Y, Christensen LM, et al. European Stroke Organisation (ESO) guideline on pharmacological interventions for long-term secondary prevention after ischaemic Stroke or transient ischaemic Attack. Eur Stroke J. 2022;7:I–II.
doi: 10.1177/23969873221100032
pubmed: 36082250
pmcid: 9446324
Gladstone DJ, Lindsay MP, Douketis J, et al. Canadian Stroke best practice recommendations: secondary Prevention of Stroke Update 2020. Can J Neurol Sci. 2022;49:315–37.
doi: 10.1017/cjn.2021.127
pubmed: 34140063
John S, Katzan I. Recurrent Stroke while on Antiplatelet Therapy. Neurol Clin. 2015;33:475–89.
doi: 10.1016/j.ncl.2014.12.007
pubmed: 25907917
Stahmeyer JT, Stubenrauch S, Geyer S, Weissenborn K, Eberhard S. The frequency and timing of recurrent Stroke: An Analysis of Routine Health Insurance Data. Dtsch Arztebl Int. 2019;116:711–17.
pubmed: 31711561
Shah J, Liu S, Yu W. Contemporary antiplatelet therapy for secondary Stroke prevention: a narrative review of current literature and guidelines. Stroke Vasc Neurol. 2022;7:406–14.
doi: 10.1136/svn-2021-001166
pubmed: 35393359
pmcid: 9614124
Lee CR, Luzum JA, Sangkuhl K, et al. Clinical pharmacogenetics implementation Consortium Guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022;112:959–67.
doi: 10.1002/cpt.2526
pubmed: 35034351
Sangkuhl K, Klein TE, Altman RB. Clopidogrel pathway. Pharmacogenet Genomics. 2010;20:463–5.
doi: 10.1097/FPC.0b013e3283385420
pubmed: 20440227
pmcid: 3086847
Ford NF. The metabolism of Clopidogrel: CYP2C19 is a minor pathway. J Clin Pharmacol. 2016;56:1474–83.
doi: 10.1002/jcph.769
pubmed: 27196064
Kim KA, Park PW, Hong SJ, Park JY. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008;84:236–42.
doi: 10.1038/clpt.2008.20
pubmed: 18323861
Pan Y, Chen W, Xu Y, et al. Genetic polymorphisms and Clopidogrel Efficacy for Acute ischemic Stroke or transient ischemic Attack: a systematic review and Meta-analysis. Circulation. 2017;135:21–33.
doi: 10.1161/CIRCULATIONAHA.116.024913
pubmed: 27806998
Spokoyny I, Barazangi N, Jaramillo V, et al. Reduced clopidogrel metabolism in a multiethnic population: prevalence and rates of recurrent cerebrovascular events. J Stroke Cerebrovasc Dis. 2014;23:694–8.
doi: 10.1016/j.jstrokecerebrovasdis.2013.06.008
pubmed: 23849748
McDonough CW, McClure LA, Mitchell BD, et al. CYP2C19 metabolizer status and clopidogrel efficacy in the secondary Prevention of small subcortical strokes (SPS3) study. J Am Heart Assoc. 2015;4:e001652.
doi: 10.1161/JAHA.114.001652
pubmed: 26019129
pmcid: 4599525
Hoh BL, Gong Y, McDonough CW, et al. CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic Disease. J Neurosurg. 2016;124:1746–51.
doi: 10.3171/2015.6.JNS15795
pubmed: 26587656
Yan Y, Hao R, Zhao X et al. Relationship between CYP2C19*2, *3 gene polymorphism and the recurrence in ischemic Stroke patients treated with clopidogrel in China: a meta-analysis. J Stroke Cerebrovasc 2022; Dis 31(11):106798.
McDermott JH, Leach M, Sen D, et al. The role of CYP2C19 genotyping to guide antiplatelet therapy following ischemic Stroke or transient ischemic Attack. Expert Rev Clin Pharmacol. 2022;15:811–25.
doi: 10.1080/17512433.2022.2108401
pubmed: 35912831
pmcid: 9612933
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
doi: 10.1136/bmj.n71
pubmed: 33782057
pmcid: 8005924
Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic Stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41.
doi: 10.1161/01.STR.24.1.35
pubmed: 7678184
Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. 2010;1:97–111.
doi: 10.1002/jrsm.12
pubmed: 26061376
Sen HM, Silan F, Silan C, Degirmenci Y, Ozisik Kamaran HI. Effects of CYP2C19 and P2Y12 gene polymorphisms on clinical results of patients using clopidogrel after Acute Ischemic Cerebrovascular Disease. Balkan J Med Genet. 2015;17:37–41.
doi: 10.2478/bjmg-2014-0072
pubmed: 25937796
pmcid: 4413440
Tornio A, Flynn R, Morant S, et al. Investigating Real-World Clopidogrel Pharmacogenetics in Stroke using a Bioresource Linked to Electronic Medical records. Clin Pharmacol Ther. 2018;103:281–6.
doi: 10.1002/cpt.780
pubmed: 28653333
Tomek A, Matʼoška V, Frýdmanová A, et al. Impact of CYP2C19 polymorphisms on clinical outcomes and antiplatelet potency of Clopidogrel in caucasian poststroke survivors. Am J Ther. 2018;25:e202–12.
doi: 10.1097/MJT.0000000000000416
pubmed: 29509167
Meschia JF, Walton RL, Farrugia LP, et al. Efficacy of Clopidogrel for Prevention of Stroke based on CYP2C19 allele Status in the POINT trial. Stroke. 2020;51:2058–65.
doi: 10.1161/STROKEAHA.119.028713
pubmed: 32568642
pmcid: 9523583
Minderhoud C, Otten LS, Hilkens PHE, van den Broek MPH, Harmsze AM. Increased frequency of CYP2C19 loss-of-function alleles in clopidogrel-treated patients with recurrent cerebral ischemia. Br J Clin Pharmacol. 2022;88:3335–40.
doi: 10.1111/bcp.15282
pubmed: 35176816
Virani SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2020 update: a Report from the American Heart Association. Circulation. 2020;141(9):e139–e596.
doi: 10.1161/CIR.0000000000000757
pubmed: 31992061
Wafa HA, Wolfe CDA, Emmett E, et al. Burden of Stroke in Europe: thirty-year projections of incidence, prevalence, deaths, and disability-adjusted life years. Stroke. 2020;51:2418–27.
doi: 10.1161/STROKEAHA.120.029606
pubmed: 32646325
pmcid: 7382540
GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 Diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of Disease Study 2019. Lancet. 2020;396:1204–22.
doi: 10.1016/S0140-6736(20)30925-9
Gorelick PB. The future of Stroke prevention by risk factor modification. Handb Clin Neurol. 2009;94:1261–76.
doi: 10.1016/S0072-9752(08)94063-X
pubmed: 18793900
Royal Dutch Pharmacists Association (KNMP). Dutch Pharmacogenetics Working Group (DPWG). Pharmacogenetic Guidelines, Netherlands. Clopidogrel – CYP2C19, https://www.knmp.nl/dossiers/farmacogenetica (Accessed 1st August 2023).
Anderson CD, Biffi A, Greenberg SM, Rosand J. Personalized approaches to clopidogrel therapy: are we there yet? Stroke. 2010;41:2997–3002.
doi: 10.1161/STROKEAHA.110.594069
pubmed: 21030701
pmcid: 3014683
Bliden KP, Baker BA, Nolin TD, et al. Thienopyridine efficacy and cigarette Smoking status. Am Heart J. 2013;165:693–703.
doi: 10.1016/j.ahj.2012.12.024
pubmed: 23622905
Zhao ZG, Chen M, Peng Y, et al. The impact of Smoking on clinical efficacy and pharmacodynamic effects of clopidogrel: a systematic review and meta-analysis. Heart. 2014;100:192–9.
doi: 10.1136/heartjnl-2013-304138
pubmed: 23749792
Angiolillo DJ, Capodanno D, Danchin N, et al. Derivation, validation, and Prognostic Utility of a prediction rule for nonresponse to Clopidogrel: the ABCD-GENE score. JACC Cardiovasc Interv. 2020;13:606–17.
doi: 10.1016/j.jcin.2020.01.226
pubmed: 32139218
Dai L, Xu J, Yan H, et al. Application of Age, Body Mass Index, chronic Kidney Disease, Diabetes, and genotyping score for efficacy of Clopidogrel: secondary analysis of the CHANCE trial. Stroke. 2022;53:465–72.
doi: 10.1161/STROKEAHA.120.033049
pubmed: 34666508
Shuldiner AR, O’Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849–57.
doi: 10.1001/jama.2009.1232
pubmed: 19706858
pmcid: 3641569
Jeong YH, Tantry US, Kim IS, et al. Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in east Asian acute Myocardial Infarction survivors treated with clopidogrel and aspirin. Circ Cardiovasc Interv. 2011;4:585–94.
doi: 10.1161/CIRCINTERVENTIONS.111.962555
pubmed: 22045970
Paré G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010;363:1704–14.
doi: 10.1056/NEJMoa1008410
pubmed: 20979470