**7. Current evidence of short- and long-term outcomes after LAAO**

The difficulties in managing patients with AF and high bleeding risk pursued a new approach of stroke prevention in AF patients. The first randomized study of LAAC with Watchman device, PROTECT AF [21], which was published in 2009, showed non-inferiority results as compared with standard warfarin therapy. This study randomized AF patients with a CHADS2 score ≥ 1, to either Watchman implantation or OAC with warfarin. At 1.5 years of follow-up, it is shown that LAAC was equivalent for stroke prevention or all-cause mortality. The efficacy of LAA occlusion was also demonstrated in a longer-term follow-up of PROTECT AF trial. At a mean follow-up of 2.3 years, the primary efficacy endpoint is shown to be non-inferior for device [35].

Similar results were shown by the second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy) [36]. The PREVAIL trial has given additional information to PROTECT AF trial by a Bayesian non-inferiority design approach. The study showed that LAAO with the Watchman device was not non-inferior to warfarin for the primary efficacy composite endpoint, including all-cause stroke, cardiovascular or unexplained death, and serious events (SE). In addition, LAAO was non-inferior to warfarin for the occurrence of late ischemic events after the first 7 days following randomization. Furthermore, the safety endpoint and successful rate of LAAO are high, even in the center with high numbers of limited experience operators of LAAO implantation within a higher-risk patient population.

In a long-term 5-year outcomes report from the PREVAIL trial and PROTECT AF trial [37], it was demonstrated that LAAC with the Watchman device provides a similar degree of stroke prevention in non-valvular AF patients to OAC with warfarin. Furthermore, with its ability to minimize major bleeding, particularly hemorrhagic stroke. LAAC results in less death than Warfarin [37].

The more recent randomized prospective, multicenter, randomized noninferiority study, PRAGUE-17, compared two treatment strategies in moderate to high-risk AF patients (i.e., patients with history of significant bleeding or history of cardiovascular event(s) or a with CHA2DS2VASc ≥3 and HAS-BLED score ≥ 2) [38]. This study randomized 402 patients with AF into percutaneous LAAC versus NOAC. After median follow-up of 3.5 year, LAAC was shown to be non-inferior to DOACs for the primary endpoint and the components of the composite endpoint, such as cardiovascular death, all-stroke/transient ischemic attack, clinically relevant bleeding, and for nonprocedural clinically relevant bleeding [39].
