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