Incidence of Device-Related Thrombosis in Watchman Patients Undergoing a Genotype-Guided Antithrombotic Strategy.

Clopidogrel / adverse effects Fibrinolytic Agents Genotype Humans Incidence Thrombosis / drug therapy
Watchman atrial fibrillation clopidogrel device-related thrombus left atrial appendage stroke

Journal

JACC. Clinical electrophysiology
ISSN: 2405-5018
Titre abrégé: JACC Clin Electrophysiol
Pays: United States
ID NLM: 101656995

Informations de publication

Date de publication:
12 2021
Historique:
received: 02 12 2020
revised: 19 04 2021
accepted: 26 04 2021
pubmed: 5 7 2021
medline: 3 2 2022
entrez: 4 7 2021
Statut: ppublish

Résumé

This study sought to report the incidence of device-related thrombosis (DRT) and thromboembolic (TE) events when an alternative to clopidogrel is prescribed in loss-of-function (LOF) allele carriers of the cytochrome P450 2C19 (CYP2C19) gene. LOF polymorphisms of the CYP2C19 gene are associated with reduced hepatic bioactivation of clopidogrel. A total of 1,002 Watchman patients were included. Six hundred forty-five patients underwent CYP2C19 genetic testing; among patients with clopidogrel resistance, clopidogrel was replaced by either prasugrel (pilot cohort) or half dose direct oral anticoagulant ([DOAC]/Group 1), both in combination with aspirin. We compared the incidence of DRT/TE events among genotyped patients and a control group which received standard dual antiplatelet therapy (DAPT) (Group 2; n = 357). All reported events occurred during a timeframe between 45- and 180-day follow-up transesophageal echocardiograms, when the 2 different antithrombotic strategies (genotype-guided vs standard DAPT) were adopted. In the pilot cohort (n = 244), bleeding events occurred in 10.2% of patients who received aspirin plus prasugrel, leading to early discontinuation of the prasugrel-based protocol. DOAC Group 1 patients (n = 401), 25.7% were reduced metabolizers, and clopidogrel was replaced by half dose direct oral anticoagulant. DRT was documented in 1 (0.2%) patient of Group 1 and 7 (1.96%) patients of Group 2 (log-rank P = 0.021). The composite endpoint of DRT/TE events was significantly lower among patients receiving a genotype-guided antithrombotic strategy (0.75% vs 3.10%; log-rank P = 0.017). In Watchman patients, a genotype-based antithrombotic strategy with aspirin plus half dose DOAC in reduced clopidogrel metabolizers was superior to standard DAPT with respect to DRT/TE events.

Sections du résumé

OBJECTIVES
This study sought to report the incidence of device-related thrombosis (DRT) and thromboembolic (TE) events when an alternative to clopidogrel is prescribed in loss-of-function (LOF) allele carriers of the cytochrome P450 2C19 (CYP2C19) gene.
BACKGROUND
LOF polymorphisms of the CYP2C19 gene are associated with reduced hepatic bioactivation of clopidogrel.
METHODS
A total of 1,002 Watchman patients were included. Six hundred forty-five patients underwent CYP2C19 genetic testing; among patients with clopidogrel resistance, clopidogrel was replaced by either prasugrel (pilot cohort) or half dose direct oral anticoagulant ([DOAC]/Group 1), both in combination with aspirin. We compared the incidence of DRT/TE events among genotyped patients and a control group which received standard dual antiplatelet therapy (DAPT) (Group 2; n = 357). All reported events occurred during a timeframe between 45- and 180-day follow-up transesophageal echocardiograms, when the 2 different antithrombotic strategies (genotype-guided vs standard DAPT) were adopted.
RESULTS
In the pilot cohort (n = 244), bleeding events occurred in 10.2% of patients who received aspirin plus prasugrel, leading to early discontinuation of the prasugrel-based protocol. DOAC Group 1 patients (n = 401), 25.7% were reduced metabolizers, and clopidogrel was replaced by half dose direct oral anticoagulant. DRT was documented in 1 (0.2%) patient of Group 1 and 7 (1.96%) patients of Group 2 (log-rank P = 0.021). The composite endpoint of DRT/TE events was significantly lower among patients receiving a genotype-guided antithrombotic strategy (0.75% vs 3.10%; log-rank P = 0.017).
CONCLUSIONS
In Watchman patients, a genotype-based antithrombotic strategy with aspirin plus half dose DOAC in reduced clopidogrel metabolizers was superior to standard DAPT with respect to DRT/TE events.

Identifiants

DOI: 10.1016/j.jacep.2021.04.012 PMID: 34217665
pubmed: 34217665
pii: S2405-500X(21)00423-0
doi: 10.1016/j.jacep.2021.04.012
pii:
doi:

Substances chimiques

Fibrinolytic Agents 0
Clopidogrel A74586SNO7

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1533-1543

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Auteurs

Domenico G Della Rocca (DG)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA. Electronic address: domenicodellarocca@hotmail.it.

Rodney P Horton (RP)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Luigi Di Biase (L)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Carola Gianni (C)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Chintan Trivedi (C)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Sanghamitra Mohanty (S)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Alisara Anannab (A)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiovascular Intervention, Central Chest Institute of Thailand, Nonthaburi, Thailand.

Michele Magnocavallo (M)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Qiong Chen (Q)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Henan Provincial People's Hospital, Zhengzhou, Henan Province, China.

Nicola Tarantino (N)

Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

Mohamed Bassiouny (M)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Carlo Lavalle (C)

Department of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.

Veronica N Natale (VN)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Giovanni B Forleo (GB)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiology, Azienda Ospedaliera-Universitaria "Luigi Sacco," Milan, Italy.

Armando Del Prete (A)

Division of Cardiology, St. Maria Goretti Hospital, Latina, Italy.

Christoffel Johannes Van Niekerk (CJ)

Interventional Electrophysiology, Scripps Clinic, La Jolla, California, USA.

Amin Al-Ahmad (A)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

J David Burkhardt (JD)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

G Joseph Gallinghouse (GJ)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Javier E Sanchez (JE)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.

Dhanunjaya Lakkireddy (D)

Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kansas, USA.

Douglas N Gibson (DN)

Interventional Electrophysiology, Scripps Clinic, La Jolla, California, USA.

Andrea Natale (A)

Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Interventional Electrophysiology, Scripps Clinic, La Jolla, California, USA; Department of Cardiology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

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Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Thiénopyridines › Ticlopidine › Clopidogrel › Incidence of Device-Related Thrombosis in...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents hématologiques › Fibrinolytiques › Incidence of Device-Related Thrombosis in...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Incidence of Device-Related Thrombosis in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Incidence of Device-Related Thrombosis in...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Morbidité › Incidence › Incidence of Device-Related Thrombosis in...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thrombose › Incidence of Device-Related Thrombosis in...