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, Taverne, Cardiology and Cardiovascular Medicine
ISSN: 0167-5273
Publisher: Elsevier Ireland Ltd.
Note: Funding Information: AvtH reports grants from Medtronic, Astra Zeneca and Sanofi and personal fees from Astra Zeneca and AMGEN; CvB reports institutional research grants provided by the research department of Thoraxcentrum Twente, from Abbott Vascular, Biotronik, Boston Scientific, and Medtronic, outside the submitted work; EB reports personal fees from BOSTON SCIENTIFIC, ABBOTT VASCULAR and GE; JtB reports grants from Astra Zeneca and personal fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, the Medicines Company, Accumetrics, Boehringer-Ingelheim, Bayer, BMS, Pfizer and Ferrer; WJ and his department have received research grants from Amgen, Athera, AstraZeneca, Biotronik, Boston Scientific, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Pfizer, Roche, Sanofi Aventis, The Medicine Company, the Netherlands Heart Foundation, Netherlands CardioVascular Research, the Netherlands Heart Institute, and the European Community Framework KP7 Programme; and was a speaker (with and without lecture fees) on amongst others (Continuing Medical Education accredited) meetings sponsored by Amgen, Athera, AstraZeneca, Biotronik, Boston Scientific, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Pfizer, Roche, Sanofi Aventis, The Medicine Company, the Netherlands Heart Foundation, CardioVascular Research the Netherlands, the Netherlands Heart Institute, and the European Community Framework KP7 Programme, during the conduct of the study. All other authors declare no conflicts of interests. 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
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