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

Domenico G Della Rocca; Rodney P Horton; Luigi Di Biase; Carola Gianni; Chintan Trivedi; Sanghamitra Mohanty; Alisara Anannab; Michele Magnocavallo; Qiong Chen; Nicola Tarantino; Mohamed Bassiouny; Carlo Lavalle; Veronica N Natale; Giovanni B Forleo; Armando Del Prete; Christoffel Johannes Van Niekerk; Amin Al-Ahmad; J David Burkhardt; G Joseph Gallinghouse; Javier E Sanchez; Dhanunjaya Lakkireddy; Douglas N Gibson; Andrea Natale

doi:10.1016/j.jacep.2021.04.012

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

JACC Clin Electrophysiol. 2021 Dec;7(12):1533-1543. doi: 10.1016/j.jacep.2021.04.012. Epub 2021 Jun 30.

Authors

Domenico G Della Rocca¹, Rodney P Horton², Luigi Di Biase³, Carola Gianni², Chintan Trivedi², Sanghamitra Mohanty², Alisara Anannab⁴, Michele Magnocavallo⁵, Qiong Chen⁶, Nicola Tarantino⁷, Mohamed Bassiouny², Carlo Lavalle⁸, Veronica N Natale², Giovanni B Forleo⁹, Armando Del Prete¹⁰, Christoffel Johannes Van Niekerk¹¹, Amin Al-Ahmad², J David Burkhardt², G Joseph Gallinghouse², Javier E Sanchez², Dhanunjaya Lakkireddy¹², Douglas N Gibson¹¹, Andrea Natale¹³

Affiliations

¹ Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA. Electronic address: [email protected].
² Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA.
³ 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.
⁴ Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiovascular Intervention, Central Chest Institute of Thailand, Nonthaburi, Thailand.
⁵ Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
⁶ Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Henan Provincial People's Hospital, Zhengzhou, Henan Province, China.
⁷ Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.
⁸ Department of Cardiology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
⁹ Texas Cardiac Arrhythmia Institute, St. David's Medical Center, Austin, Texas, USA; Department of Cardiology, Azienda Ospedaliera-Universitaria "Luigi Sacco," Milan, Italy.
¹⁰ Division of Cardiology, St. Maria Goretti Hospital, Latina, Italy.
¹¹ Interventional Electrophysiology, Scripps Clinic, La Jolla, California, USA.
¹² Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, Kansas, USA.
¹³ 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.

PMID: 34217665
DOI: 10.1016/j.jacep.2021.04.012

Abstract

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.

Keywords: Watchman; atrial fibrillation; clopidogrel; device-related thrombus; left atrial appendage; stroke.

MeSH terms

Clopidogrel / adverse effects
Fibrinolytic Agents*
Genotype
Humans
Incidence
Thrombosis* / drug therapy
Thrombosis* / epidemiology
Thrombosis* / genetics

Substances

Fibrinolytic Agents
Clopidogrel