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Oral anticoagulation therapy (OAC) is a mainstay for mitigating stroke and other embolic events in patients with atrial fibrillation (AF). Despite the demonstrated efficacy of OAC in reducing events, many patients are unable to tolerate OAC due to bleeding risks. Left atrial appendage occlusion (LAAO) devices were developed as implantable technologies to moderate stroke risk in patients with intolerance to OAC. Despite clinical data supporting near-comparable protection against thromboembolic events with OAC, device-related thrombus formation has emerged as a critical complication following LAAO that remains a potential limitation to the safety and efficacy of LAAO. Improved biocompatibility of LAAO devices with fluoropolymers, a well-established stent-coating technology used to reduce thrombus formation and promote endothelialization, may optimize outcomes after LAAO. Article highlights Original concept & evidence of left atrial appendage occlusion To prevent thromboembolism in nonvalvular atrial fibrillation (NVAF) patients, left atrial appendage occlusion (LAAO) technology has evolved as an alternative to oral anticoagulation therapy (OAC) in those with high bleeding risk. Randomized trials demonstrated noninferiority of LAAO in safety and efficacy compared with conventional oral OAC, with similar stroke rates and potentially lower bleeding rates. As LAAO therapy evolves, it could be a viable first-line alternative to direct oral anticoagulants in NVAF patients. Device-related thrombus after the implantation of LAAO Device-related thrombus (DRT) is a critical complication after LAAO that can lead to thromboembolic events, with incidences ranging from 1.6 to 16%. DRT is defined as a density confirmed in multiple planes on imaging transesophageal echocardiography or coronary CT angiography, which appears to be related to device, patients, and anatomical factors. DRT is associated with a higher incidence of thromboembolic events, underscoring its clinical importance. Second-generation WATCHMAN FLX device The second-generation WATCHMAN FLX is one LAAO device that has improved LAA sealing and is designed to facilitate implantation in complex LAA anatomies. The WATCHMAN FLX has demonstrated promising short-term safety and efficacy in accommodating diverse LAA structures, with a reduction in procedural complications and the incidence of DRT as compared with earlier generations. Strategies to prevent DRT Antithrombotic treatment and endothelialization after the device implantation are key to preventing DRT after LAAO. Improving thromboresistance and augmenting endothelialization after device implantation may favorably impact DRT incidence and thromboembolic events. Fluoropolymer coating technology has good biocompatibility and thromboresistance as shown in drug-eluting stents and vascular grafts. New-generation FP coated LAAO device The WATCHMAN FLX Pro device (FP-WATCHMAN) with fluoropolymer coating technology is designed to further improve hemocompatibility and reduce the incidence of DRT compared with the conventional WATCHMAN FLX. An animal study demonstrated that FP-WATCHMAN showed significantly less thrombus formation and inflammation, attributed to greater albumin adsorption which inhibits platelet adhesion and subsequent thrombus formation. FP-WATCHMAN is expected to enhance early endothelial coverage, leading to further improvements in the prevention of DRT. [ABSTRACT FROM AUTHOR]