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 Mosterd; Jean-Paul R Herrman; Willem Dewilde; Bakhtawar K Mahmoodi; Vera H M Deneer; Jurriën M Ten Berg

doi:https://doi.org/10.1016/j.ijcard.2021.04.029

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, Jurriën M Ten Berg

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	10-17
Number of pages	8
Journal	International journal of cardiology
Volume	334
DOIs	https://doi.org/10.1016/j.ijcard.2021.04.029
Publication status	Published - 1 Jul 2021
Externally published	Yes

Keywords

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

Access to Document

https://doi.org/10.1016/j.ijcard.2021.04.029

Cite this

Claassens, D. M. F., Gimbel, M. E., Bergmeijer, T. O., Vos, G. J. A., Hermanides, R. S., van der Harst, P., Barbato, E., Morisco, C., Tjon Joe Gin, R. M., de Vrey, E. A., Heestermans, T. A. C. M., Jukema, J. W., von Birgelen, C., Waalewijn, R. A., Hofma, S. H., den Hartog, F. R., Voskuil, M., Van't Hof, A. W. J., Asselbergs, F. W., ... Ten Berg, J. M. (2021). 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. International journal of cardiology, 334, 10-17. https://doi.org/10.1016/j.ijcard.2021.04.029

Claassens, Daniel M F ; Gimbel, Marieke E ; Bergmeijer, Thomas O et al. / 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. In: International journal of cardiology. 2021 ; Vol. 334. pp. 10-17.

@article{99e43b9f95e443fa95556958305247be,

title = "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.",

keywords = "Acute Coronary Syndrome/diagnosis, Aged, Aged, 80 and over, Alleles, Clopidogrel/therapeutic use, Cytochrome P-450 CYP2C19/genetics, Genotype, Humans, Platelet Aggregation Inhibitors, Ticagrelor, Treatment Outcome",

author = "Claassens, {Daniel M F} and Gimbel, {Marieke E} and Bergmeijer, {Thomas O} and Vos, {Gerrit J A} and Hermanides, {Renicus S} and {van der Harst}, Pim and Emanuele Barbato and Carmine Morisco and {Tjon Joe Gin}, {Richard M} and {de Vrey}, {Evelyn A} and Heestermans, {Ton A C M} and Jukema, {J Wouter} and {von Birgelen}, Clemens and Waalewijn, {Reinier A} and Hofma, {Sjoerd H} and {den Hartog}, {Frank R} and Michiel Voskuil and {Van't Hof}, {Arnoud W J} and Asselbergs, {Folkert W} and A Mosterd and Herrman, {Jean-Paul R} and Willem Dewilde and Mahmoodi, {Bakhtawar K} and Deneer, {Vera H M} and {Ten Berg}, {Jurri{\"e}n M}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier B.V.",

year = "2021",

month = jul,

day = "1",

doi = "https://doi.org/10.1016/j.ijcard.2021.04.029",

language = "English",

volume = "334",

pages = "10--17",

journal = "International journal of cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

Claassens, DMF, Gimbel, ME, Bergmeijer, TO, Vos, GJA, Hermanides, RS, van der Harst, P, Barbato, E, Morisco, C, Tjon Joe Gin, RM, de Vrey, EA, Heestermans, TACM, Jukema, JW, von Birgelen, C, Waalewijn, RA, Hofma, SH, den Hartog, FR, Voskuil, M, Van't Hof, AWJ, Asselbergs, FW, Mosterd, A, Herrman, J-PR, Dewilde, W, Mahmoodi, BK, Deneer, VHM & Ten Berg, JM 2021, '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', International journal of cardiology, vol. 334, pp. 10-17. https://doi.org/10.1016/j.ijcard.2021.04.029

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 et al.
In: International journal of cardiology, Vol. 334, 01.07.2021, p. 10-17.

Research output: Contribution to journal › Article › Academic › peer-review

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

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 - Acute Coronary Syndrome/diagnosis

KW - Aged

KW - Aged, 80 and over

KW - Alleles

KW - Clopidogrel/therapeutic use

KW - Cytochrome P-450 CYP2C19/genetics

KW - Genotype

KW - Humans

KW - Platelet Aggregation Inhibitors

KW - Ticagrelor

KW - Treatment Outcome

U2 - https://doi.org/10.1016/j.ijcard.2021.04.029

DO - https://doi.org/10.1016/j.ijcard.2021.04.029

M3 - Article

C2 - 33887342

SN - 0167-5273

VL - 334

SP - 10

EP - 17

JO - International journal of cardiology

JF - International journal of cardiology

ER -

Claassens DMF, Gimbel ME, Bergmeijer TO, Vos GJA, Hermanides RS, van der Harst P et al. 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. International journal of cardiology. 2021 Jul 1;334:10-17. doi: https://doi.org/10.1016/j.ijcard.2021.04.029