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

Daniel M. F. Claassens, Marieke E. Gimbel, Thomas O. Bergmeijer, Gerrit J. A. Vos, Renicus S. Hermanides, Pim van der Harst, Emanuele Barbato, Carmine Morisco, Richard M. Tjon Joe Gin, Evelyn A. de Vrey, Ton A. C. M. Heestermans, J. Wouter Jukema, Clemens von Birgelen, Reinier A. Waalewijn, Sjoerd H. Hofma, Frank R. den Hartog, Michiel Voskuil, Arnoud W. J. Van't Hof, Folkert W. Asselbergs, A. MosterdJean-Paul R. Herrman, Willem Dewilde, Bakhtawar K. Mahmoodi, Vera H. M. Deneer, Jurrien M. ten Berg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)10-17
Number of pages8
JournalInternational Journal of Cardiology
Publication statusPublished - 1-Jul-2021


  • Pharmacogenetics
  • Older
  • Genotyping
  • Myocardial infarction
  • ABCB1

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