TY - JOUR
T1 - Clopidogrel in noncarriers of CYP2C19 loss-of-function alleles versus ticagrelor in elderly patients with acute coronary syndrome
T2 - A pre-specified sub analysis from the POPular Genetics and POPular Age trials CYP2C19 alleles in elderly patients
AU - Claassens, Daniel M.F.
AU - Gimbel, Marieke E.
AU - Bergmeijer, Thomas O.
AU - Vos, Gerrit J.A.
AU - Hermanides, Renicus S.
AU - van der Harst, Pim
AU - Barbato, Emanuele
AU - Morisco, Carmine
AU - Tjon Joe Gin, Richard M.
AU - de Vrey, Evelyn A.
AU - Heestermans, Ton A.C.M.
AU - Jukema, J. Wouter
AU - von Birgelen, Clemens
AU - Waalewijn, Reinier A.
AU - Hofma, Sjoerd H.
AU - den Hartog, Frank R.
AU - Voskuil, Michiel
AU - van't Hof, Arnoud W.J.
AU - Asselbergs, Folkert W.
AU - Mosterd, A.
AU - Herrman, Jean Paul R.
AU - Dewilde, Willem
AU - Mahmoodi, Bakhtawar K.
AU - Deneer, Vera H.M.
AU - ten Berg, Jurriën M.
N1 - 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
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
KW - CYP2C19
KW - Genotyping
KW - Myocardial infarction
KW - Older
KW - P2Y12
KW - Pharmacogenetics
KW - n/a OA procedure
UR - https://www.scopus.com/pages/publications/85106259701
U2 - 10.1016/j.ijcard.2021.04.029
DO - 10.1016/j.ijcard.2021.04.029
M3 - Article
C2 - 33887342
AN - SCOPUS:85106259701
SN - 0167-5273
VL - 334
SP - 10
EP - 17
JO - International journal of cardiology
JF - International journal of cardiology
ER -
