B-PO02-157 INCIDENCE OF DEVICE-RELATED THROMBOSIS IN WATCHMAN PATIENTS UNDERGOING A GENOTYPE-GUIDED ANTITHROMBOTIC STRATEGY

Abstract

Loss of Function (LOF) polymorphisms of cytochrome P450 2C19 (CYP2C19) are associated with reduced hepatic bioactivation of clopidogrel. To report the incidence of device-related thrombosis (DRT) and thromboembolic (TE) events when an alternative to clopidogrel is prescribed in patients with a LOF allele of CYP2C19 gene. Among 1002 Watchman patients, 645 underwent CYP2C19 genetic testing; among patients with clopidogrel resistance, clopidogrel was replaced by either prasugrel (pilot cohort) or half dose novel oral anticoagulant (NOAC; 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 TEEs, when the genotype-guided or standard DAPT strategies were adopted. In the pilot cohort (n=244), bleeding events occurred in 10.2% of patients receiving prasugrel, leading to discontinuation of the prasugrel-based protocol. Among Group 1 patients (n=401), 25.7% were reduced metabolizers and clopidogrel was replaced with half dose NOAC. DRT was documented in 1 (0.2%) patient of Group 1 and 7 (1.96%) of Group 2 (log-rank p-value=0.021). The composite endpoint of DRT/TE events was significantly lower among patients receiving a genotype-guided strategy (0.75% vs. 3.1%; log-rank p-value=0.017). In Watchman patients, a genotype-based antithrombotic strategy with aspirin plus half dose NOAC in reduced clopidogrel metabolizers was superior to standard DAPT with respect to DRT/TE events.