Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome: A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:334

Article

Claassens, Daniel M. F.^1,2  Gimbel, Marieke E.¹  Bergmeijer, Thomas O.¹  Vos, Gerrit J. A.¹  Hermanides, Renicus S.²  van der Harst, Pim^3,4  Barbato, Emanuele^5,6  Morisco, Carmine⁵  Gin, Richard M. Tjon Joe⁷  de Vrey, Evelyn A.⁸  Heestermans, Ton A. C. M.⁹  Jukema, J. Wouter¹⁰  von Birgelen, Clemens¹¹  Waalewijn, Reinier A.¹²  Hofma, Sjoerd H.¹³  den Hartog, Frank R.¹⁴  Voskuil, Michiel⁴  Van't Hof, Arnoud W. J.^2,15,16,17  Asselbergs, Folkert W.^4,18,19,20  Mosterd, A.⁷  Herrman, Jean-Paul R.²¹  Dewilde, Willem²²  Mahmoodi, Bakhtawar K.¹  Deneer, Vera H. M.^23,24  ten Berg, Jurrien M.^1,17 

[1] St Antonius Hosp, Dept Cardiol, Koekoekslaan 1, NL-3435 CM Nieuwegein, Netherlands

[2] Isala Hosp, Dept Cardiol, Zwolle, Netherlands

[3] Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[4] Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands

[5] Univ Naples Federico II, Dept Adv Biomed Sci, Naples, Italy

[6] Onze Lieve Vrouw Hosp, Cardiovasc Res Ctr, Aalst, Belgium

[7] Rijnstate Hosp, Dept Cardiol, Arnhem, Netherlands

[8] Meander Med Ctr, Dept Cardiol, Amersfoort, Netherlands

[9] Noord West Hosp Grp, Dept Cardiol, Alkmaar, Netherlands

[10] Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands

[11] Med Spectrum Twente, Dept Cardiol, Enschede, Netherlands

[12] Gelre Hosp, Dept Cardiol, Apeldoorn, Netherlands

[13] Med Ctr Leeuwarden, Dept Cardiol, Leeuwarden, Netherlands

[14] Gelderse Vallei Hosp, Dept Cardiol, Ede, Netherlands

[15] Univ Med Ctr Maastricht, Dept Cardiol, Maastricht, Netherlands

[16] Zuyderland Med Ctr, Dept Cardiol, Heerlen, Netherlands

[17] Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands

[18] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England

[19] UCL, Hlth Data Res UK, London, England

[20] UCL, Inst Hlth Informat, London, England

[21] Onze Lieve Vrouw Hosp, Dept Cardiol, Amsterdam, Netherlands

[22] Imelda Hosp, Dept Cardiol, Bonheiden, Belgium

[23] Univ Med Ctr Utrecht, Dept Clin Pharm, Div Labs Pharm & Biomed Genet, Utrecht, Netherlands

[24] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands

关键词: Pharmacogenetics;    Older;    Genotyping;    Myocardial infarction;   

DOI  :  10.1016/j.ijcard.2021.04.029

来源: Elsevier

【 摘 要 】

Background: Patients with acute coronary syndrome (ACS) who are carrying CYP2C19 loss-of-function alleles derive less benefit from clopidogrel treatment. Despite this, in elderly patients, clopidogrel might be preferred over more potent P2Y12 inhibitors due to a lower bleeding risk. Whether CYP2C19 genotype-guided antiplatelet treatment in the elderly could be of benefit has not been studied specifically. Methods: Patients aged 70 years and older with known CYP2C19*2 and *3 genotype were identified from the POPular Genetics and POPular Age trials. Noncarriers of loss-of-function alleles treated with clopidogrel were compared to patients, irrespective of CYP2C19 genotype, treated with ticagrelor and to clopidogrel treated carriers of loss-of-function alleles. We assessed net clinical benefit (all-cause death, myocardial infarction, stroke and Platelet Inhibition and Patient Outcomes (PLATO) major bleeding), atherothrombotic outcomes (cardiovascular death, myocardial infarction, stroke) and bleeding outcomes (PLATO major and minor bleeding). Results: A total of 991 patients were assessed. There was no significant difference in net clinical benefit (17.2% vs. 15.1%, adjusted hazard ratio (adjHR) 1.05, 95% confidence interval (CI) 0.77-1.44), atherothrombotic outcomes (9.7% vs. 9.2%, adjHR 1.00, 95%CI 0.66-1.50), and bleeding outcomes (17.7% vs. 19.8%, adjHR 0.80, 95%CI 0.62-1.12) between clopidogrel in noncarriers of loss-of-function alleles and ticagrelor respectively. Conclusion: In ACS patients aged 70 years and older, there was no significant difference in net clinical benefit and atherothrombotic outcomes between noncarriers of a loss-of-function allele treated with clopidogrel and pa-tients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in pa-tients using clopidogrel. (c) 2021 Published by Elsevier B.V.

【 授权许可】

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