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.

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 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.

• Authors: 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 Mosterd, Jean-Paul R Herrman, Willem Dewilde, Bakhtawar K Mahmoodi, Vera H M Deneer, Jurriën M Ten Berg
• Journal: International journal of cardiology (Int J Cardiol) Vol. 334 Pg. 10-17 (Jul 01 2021) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 33887342 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Ticagrelor

Topics

• Acute Coronary Syndrome (diagnosis, drug therapy, genetics)
• Aged
• Aged, 80 and over
• Alleles
• Clopidogrel (therapeutic use)
• Cytochrome P-450 CYP2C19 (genetics)
• Genotype
• Humans
• Platelet Aggregation Inhibitors
• Ticagrelor
• Treatment Outcome