Clinical Electrophysiology -> Atrial Fibrillation & Atrial Flutter: -> Left Atrial Appendage Closure D-AB28 - Left Atrial Appendage Closure- Trials and Tribulations (ID 32) Abstract Plus

D-AB28-06 - Lower Rate Of Device Related Thrombosis In Watchman Patients Undergoing An Anti-thrombotic Strategy Based On Genetic Assessment Of Clopidogrel Metabolism (ID 1470)


Background: Clopigodrel is used after Watchman implant to prevent device-related thrombosis (DRT) that might occur before endothelialization is complete. Loss-of-function (LOF) polymorphisms of the cytochrome P450 2C19 (CYP2C19) gene are associated with reduced hepatic bioactivation of clopidogrel.
Objective: To evaluate the prevalence of LOF polymorphisms of CYP2C19 and the incidence of DRT when clopidogrel is replaced with half dose of novel oral anticoagulant (OAC) in patients with reduced metabolism.
Methods: Watchman patients were genotyped for CYP2C19 polymorphisms with an assay using a polymerase chain reaction with allele-specific primer extension. Patients with reduced metabolism were considered resistant to clopidogrel and received half dose of novel OAC plus ASA during the “dual anti-platelet therapy (DAPT) phase” post-Watchman (between 45 days and 6 months post-implant). The incidence of DRT among genotyped patients (Group I) and a control group without genotypization (Group II) that received standard DAPT is reported.
Results: Overall, 401 patients (mean age: 74±8 yrs, 64% males, CHA2DS2-VASc: 4.5±1.5; HAS-BLED: 3.2±1.1) were genotyped for CYP2C19 polymorphisms (Group I). Of them, 38.6% were normal metabolizers, 30.7% increased, 30.7% reduce and reduced to normal. Among patients with clopidogrel resistance (n=123), 72.3% (n=89) were prescribed with aspirin plus half dose of novel OAC, 13.0% (n=16) were kept on ASA plus OAC due to the presence of a significant peri-device leak, and the remaining 14.6% (n=18) had a history of cerebrovascular accident and received ASA and clopidogrel. Mean age, CHA2DS2-VASc, HAS-BLED, and follow-up duration were not different between Group I and Group II (control group, n=276). During the “DAPT phase”, DRT was observed in 1 (0.2%) patient of Group I and 7 (2.5%) of Group II (p=0.009). On multivariate analysis, the genetic-based anti-thrombotic strategy was the only predictor of DRT (OR:0.033; 95% CI: 0.003 - 0.337; p-value: 0.004).
Conclusion: Approximately 30% of our Watchman patients had clopidogrel resistance. In our population, substitution of clopidogrel with half dose of novel OAC in patients with reduced metabolism significantly decreased the incidence of DRT.