TY - JOUR
T1 - Incidence of Device-Related Thrombosis in Watchman Patients Undergoing a Genotype-Guided Antithrombotic Strategy
AU - Della Rocca, Domenico G.
AU - Horton, Rodney P.
AU - Di Biase, Luigi
AU - Gianni, Carola
AU - Trivedi, Chintan
AU - Mohanty, Sanghamitra
AU - Anannab, Alisara
AU - Magnocavallo, Michele
AU - Chen, Qiong
AU - Tarantino, Nicola
AU - Bassiouny, Mohamed
AU - Lavalle, Carlo
AU - Natale, Veronica N.
AU - Forleo, Giovanni B.
AU - Del Prete, Armando
AU - Van Niekerk, Christoffel Johannes
AU - Al-Ahmad, Amin
AU - Burkhardt, J. David
AU - Gallinghouse, G. Joseph
AU - Sanchez, Javier E.
AU - Lakkireddy, Dhanunjaya
AU - Gibson, Douglas N.
AU - Natale, Andrea
N1 - Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Watchman
KW - atrial fibrillation
KW - clopidogrel
KW - device-related thrombus
KW - left atrial appendage
KW - stroke
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U2 - 10.1016/j.jacep.2021.04.012
DO - 10.1016/j.jacep.2021.04.012
M3 - Article
C2 - 34217665
AN - SCOPUS:85120325412
SN - 2405-500X
VL - 7
SP - 1533
EP - 1543
JO - JACC: Clinical Electrophysiology
JF - JACC: Clinical Electrophysiology
IS - 12
ER -