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
Claassens, Daniel M F; Gimbel, Marieke E; Bergmeijer, Thomas O; Vos, Gerrit J A; Hermanides, Renicus S; van der Harst, Pim; Barbato, Emanuele; Morisco, Carmine; Tjon Joe Gin, Richard M; de Vrey, Evelyn A; Heestermans, Ton A C M; Jukema, J Wouter; von Birgelen, Clemens; Waalewijn, Reinier A; Hofma, Sjoerd H; den Hartog, Frank R; Voskuil, Michiel; Van't Hof, Arnoud W J; Asselbergs, Folkert W; Mosterd, A; Herrman, Jean-Paul R; DeWilde, Willem; Mahmoodi, Bakhtawar K; Deneer, Vera H M; Ten Berg, Jurriën M
(2021) International Journal of Cardiology, volume 334, pp. 10 - 17
(Article)
Abstract
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
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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 patients treated with ticagrelor. The bleeding rate was numerically; though not statistically significant, lower in patients using clopidogrel.
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Keywords: CYP2C19, Genotyping, Myocardial infarction, Older, P2Y12, Pharmacogenetics, Cardiology and Cardiovascular Medicine, Journal Article
ISSN: 0167-5273
Publisher: Elsevier Ireland Ltd
Note: Funding Information: Dr. Asselbergs is supported by the University College London Hospitals National Institute for Health Research Biomedical Research Centre . Funding Information: The POPular Genetics and POPular Age trial were both funded by ZonMw , a Dutch Governmental agency promoting research in healthcare. In the POPular Genetics trial, a portion of the patients was tested using point-of-care tests supplied by Spartan Bioscience Inc. for free. Publisher Copyright: © 2021
(Peer reviewed)