ABC | Volume 113, Nº4, October 2019

Short Editorial Percutaneous Occlusion of Left Atrial Appendage: Growing Clinical Experience and Lack of Multicenter Randomized Clinical Trials Cristiano F. Pisani and Mauricio Scanavacca Unidade Clínica de Arritmia do Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, SP – Brazil Short Editorial related to the article: Left Atrial Appendage Transcatheter Occlusion with AMPLATZER™ Amulet™ Device: Real Life Data with Mid‑Term Follow-Up Results Mailing Address: Cristiano F. Pisani • Unidade Clínica de Arritmia do InCor do HC-FMUSP - Av. Dr. Eneas Carvalho de Aguiar, 44. Postal Code 05403-000, São Paulo, SP – Brazil E-mail: cristianopisani@gmail.com Keywords Atrial Fibrillation/therapy; Atrial Appendage/diagnotic, imaging; Prostheses and Implants/adverse effects; Stroke/ prevention and control. DOI: 10.5935/abc.20190210 Left atrial appendage (LAA) closure as a prophylactic strategy for thromboembolic events in patients with atrial fibrillation (AF) has been performed for decades; initially during mitral valve repair surgeries 1 and, more recently, in nonvalvular AF patients at high risk of embolism who do not tolerate the use of oral anticoagulants (OACs). The ideaof LAAocclusionas analternative to chronicwarfarin use emerged from observations of anatomopathological studies and during cardiac surgery that disclosed the LAA as the main site of thrombus formation in patients with nonvalvular atrial fibrillation. 2,3 The evolution of cardiac access interventionist techniques, together with the development of specific prostheses for LAA occlusion, allowed the appendage closure to be performed percutaneously, using a minimally invasive procedure, making it simpler and not restricted to patients who would have undergone heart surgery. The first prosthesis developed for this purpose, called PLAATO, was tested early in the last decade by Horst Sievert et al. 4 and consisted of a nitinol structure, covered by an expanded polytetrafluoroethylene (ePTFE) occlusive membrane. The clinical study published in 2002 showed that the concept of percutaneous LAA occlusion was feasible; however, the prosthesis use was discontinued in 2005, due to the considerable number of complications such as cardiac tamponade, residual leaks, prosthesis protrusion towards the atrial cavity and, in some cases, lack of neo-endothelization of the prosthesis with formation of local thrombi. 5 On the other hand, the experience obtained with the implantation of this prosthesis was important for the development of more effective devices. Currently, two prostheses with different profiles are being used in clinical practice: the Watchman prosthesis sold by Boston Scientific and the Amplatzer Amulet device (evolution of the Amplatzer Cardiac Plug) sold by ABBOTT. Of these, only the Watchman prosthesis has been evaluated in two prospective, multicenter, and randomized clinical trials. The PROTECT-AF study (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation), 6 evaluated the effectiveness and safety of percutaneous LAA occlusion with the Watchman prosthesis, compared with oral anticoagulation with warfarin in 707 patients (463 in the intervention group) with nonvalvular AF and CHADS2 ≥ 1. The LAA occlusion (3 events per patient-year) met the noninferiority criterion compared to warfarin (4.9 events per patient-year) in the efficacy criterion; however, the LAA occluder implantation was associated with a higher number of adverse events, especially the occurrence of hemopericardium (4.8%), which was related to the interventionist’s learning curve in the prosthesis placement. Due to safety concerns, the study was repeated (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy – PREVAIL trial) 7 with the same characteristics as the previous one, except for the greater experience of the operators. A total of 407 patients (269 in the intervention group) were included and at 18 months of follow‑up, efficacy event rates (stroke, systemic embolization, and cardiovascular or unexplained death) of 0.064 were observed in the intervention group and 0.063 in the warfarin group, thus not meeting the pre-specified non-inferiority criteria previously obtained in the PROTEC-AF study, due to the very low number of events in the control group, a fact not observed in the previous and subsequent studies using warfarin. However, the noninferiority criterion was met in the analysis of the second primary efficacy endpoint related to the event rate after 7 days of randomization. Also positive was the lower rate of prosthesis implant complications compared with the PROTECT AF study. A complicating factor for the clinical implementation of the LAA occlusion strategy was the emergence of four new direct-acting oral anticoagulants (DOACs), supported by potent clinical studies showing no inferiority or even superiority of these new drugs over warfarin in patients with nonvalvular AF. 8,9 Due to the practical use of DOACs, the indication of appendage occlusion devices has been postponed and considered only in patients who are intolerant to oral anticoagulants, or in those who experienced embolic events while using these drugs, although the effectiveness of the device has not been studied in randomized controlled trials. Therefore, due to this heterogeneity of indications and the lack of randomized controlled trials, the records have become important. Reddy et al. 10 evaluated 3822 consecutive cases of LAA occluder implantation based on Medicare data, showing 722