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.


Journal

International journal of cardiology
ISSN: 1874-1754
Titre abrégé: Int J Cardiol
Pays: Netherlands
ID NLM: 8200291

Informations de publication

Date de publication:
01 Jul 2021
Historique:
received: 23 01 2021
revised: 09 04 2021
accepted: 16 04 2021
pubmed: 23 4 2021
medline: 5 6 2021
entrez: 22 4 2021
Statut: ppublish

Résumé

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 P2Y 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). 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. 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.

Sections du résumé

BACKGROUND 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 P2Y
METHODS 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33887342
pii: S0167-5273(21)00665-3
doi: 10.1016/j.ijcard.2021.04.029
pii:
doi:

Substances chimiques

Platelet Aggregation Inhibitors 0
Clopidogrel A74586SNO7
CYP2C19 protein, human EC 1.14.14.1
Cytochrome P-450 CYP2C19 EC 1.14.14.1
Ticagrelor GLH0314RVC

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

10-17

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Auteurs

Daniel M F Claassens (DMF)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Department of Cardiology, Isala Hospital, Zwolle, the Netherlands.

Marieke E Gimbel (ME)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Thomas O Bergmeijer (TO)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Gerrit J A Vos (GJA)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Renicus S Hermanides (RS)

Department of Cardiology, Isala Hospital, Zwolle, the Netherlands.

Pim van der Harst (P)

Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands; Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Emanuele Barbato (E)

Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy; Cardiovascular Research Center, Onze lieve Vrouwe Hospital, Aalst, Belgium.

Carmine Morisco (C)

Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy.

Richard M Tjon Joe Gin (RM)

Department of Cardiology, Rijnstate Hospital, Arnhem, the Netherlands.

Evelyn A de Vrey (EA)

Department of Cardiology, Meander Medical Center, Amersfoort, the Netherlands.

Ton A C M Heestermans (TACM)

Department of Cardiology, Noord-west Hospital group, Alkmaar, the Netherlands.

J Wouter Jukema (JW)

Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands.

Clemens von Birgelen (C)

Department of Cardiology, Medisch Spectrum Twente, Enschede, the Netherlands.

Reinier A Waalewijn (RA)

Department of Cardiology, Gelre Hospitals, Apeldoorn, the Netherlands.

Sjoerd H Hofma (SH)

Department of Cardiology, Medical Centre Leeuwarden, Leeuwarden, the Netherlands.

Frank R den Hartog (FR)

Department of Cardiology, Gelderse Vallei Hospital, Ede, the Netherlands.

Michiel Voskuil (M)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

Arnoud W J Van't Hof (AWJ)

Department of Cardiology, Isala Hospital, Zwolle, the Netherlands; Department of Cardiology, University Medical Center Maastricht, Maastricht, the Netherlands; Department of Cardiology, Zuyderland Medical Center, Heerlen, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands.

Folkert W Asselbergs (FW)

Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom; Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom.

A Mosterd (A)

Department of Cardiology, Rijnstate Hospital, Arnhem, the Netherlands.

Jean-Paul R Herrman (JR)

Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.

Willem Dewilde (W)

Department of Cardiology, Imelda Hospital, Bonheiden, Belgium.

Bakhtawar K Mahmoodi (BK)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Vera H M Deneer (VHM)

Department of Clinical Pharmacy, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University Utrecht, the Netherlands.

Jurriën M Ten Berg (JM)

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands; Cardiovascular Research Institute Maastricht (CARIM), Maastricht, the Netherlands. Electronic address: jurtenberg@gmail.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH