Abstract 17102: Lower Rate of Device-Related Thrombosis in Watchman Patients Undergoing a Genotype-Tailored Antithrombotic Strategy

Abstract

Introduction: Loss-of-function (LOF) polymorphisms of the cytochrome P450 2C19 (CYP2C19) gene are associated with reduced hepatic bioactivation of clopidogrel. Hypothesis: To evaluate the prevalence of LOF polymorphisms of CYP2C19 and the incidence of device-related thrombosis (DRT) when clopidogrel is replaced with half dose novel oral anticoagulant (NOAC) in patients with reduced clopidogrel metabolism. Methods: Consecutive Watchman patients were genotyped for CYP2C19 polymorphisms. Patients with reduced clopidogrel metabolism received half dose NOAC plus aspirin during the “dual antiplatelet therapy (DAPT) phase” post-Watchman implantation (between 45 days and 6 months). The incidence of DRT among genotyped patients (Group I, n=401) and a control group without genotypization (Group II, n=357) which received standard DAPT is reported. Results: Overall, 758 Watchman patients were included (mean age: 75±8 yrs, 63% males, CHA 2 DS 2 -VASc: 4.6±1.5; HAS-BLED: 3.2±1.1). Of the 401 Group 1 patients, 25.69% (n=103) were reduced clopidogrel metabolizers. In 87.4% of them, clopidogrel was replaced with half-dose NOAC during the “DAPT phase” post-Watchman implantation whereas 12.6% received ASA plus full-dose NOAC due to the presence of a significant peri-device leak. During the “DAPT phase”, DRT was documented in 1 (0.2%) patient of Group I and 7 (1.96%) patients of Group II (p=0.029). On multivariate analysis, a genotype-tailored antithrombotic strategy was associated with a significant reduction in DRT (odds ratio: 0.11; 95% confidence interval: 0.01 - 0.98; p-value: 0.048). Conclusions: Approximately 25% of our Watchman patients had clopidogrel resistance. Substitution of clopidogrel with half dose NOAC in reduced clopidogrel metabolizers significantly reduced the incidence of DRT.