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. SanchezDhanunjaya Lakkireddy, Douglas N. Gibson, Andrea Natale

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1533-1543
Number of pages11
JournalJACC: Clinical Electrophysiology
Issue number12
StatePublished - Dec 2021


  • Watchman
  • atrial fibrillation
  • clopidogrel
  • device-related thrombus
  • left atrial appendage
  • stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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