The most commonly used percutaneous LAAO devices are shown in figure 1 and described in Table 1. Percutaneous LAAO uses transvenous access with trans-septal puncture and was first tested using the Percutaneous LAA Transcatheter Occlusion (PLAATO) device (Appriva Medical Inc., Sunnyvale, CA) in 2001.
The Watchman device (Boston Scientific, Marlborough, MA), is the only FDA-approved percutaneous device for LAAO. The device is composed of self-expanding nitinol frame structure with fixation barbs and a permeable polyester fabric that covers the atrial facing surface of the device (Table 1). Multiple trials were done to evaluate the safety, efficacy and outcomes of watchmen device.
Pilot study was a non-randomized trial that included 75 patients and was done to assess the feasibility and safety of watchman device. They enrolled adult patients who: had non-valvular AF for 2 years, were eligible for warfarin therapy, and had CHADS2 of at least 1. Although this was the first human trial to evaluate the efficacy and safety of Watchman device, the success rate of LAAO was very high and complications were relatively low. 88% of patients had successful device implantation and 93% of them had complete LAAO. Reported complications included; device embolization in 2 patients, device-related thrombus formation in 4 patients, and transient ischemic attack in 2 patients. There was no reported major strokes or procedure-related mortality.
PROTECT AF study (WATCHMAN LAA System for Embolic Protection in Patients with Atrial Fibrillation) was the first randomized trial to compare the efficacy and safety of LAAO using Watchman device with chronic warfarin therapy in patients with non-valvular AF and had CHADS2 of 1 or more. Exclusion criteria included contraindications to warfarin, chronic warfarin use, LAA thrombus, a patent foramen ovale with atrial septal aneurysm and right-to-left shunt, mobile aortic atheroma, and symptomatic carotid artery disease. This trial enrolled 707 patients from 59 centers worldwide and assigned them randomly to LAAO with Watchman device (n = 463) or warfarin therapy (n = 244) with INR goal of 2 to 3. Watchman group was treated with warfarin for 45 d after device deployment to allow proper endothelialization. Warfarin was discontinued if TEE showed complete closure or significantly decreased flow around the device. Afterward, patients were given aspirin and clopidogrel for 6 mo followed by lifelong aspirin. At 1065 patient-years (PY) of follow-up (mean follow up 18 mo), Watchman device was non-inferior to warfarin for primary efficacy endpoint of stroke (either ischemic or hemorrhagic), cardiovascular death, or systemic thromboembolism. The Event rates of primary efficacy endpoint were 3% and 4.9% for Watchman and warfarin groups, respectively. Since then, two studies were published with two different follow up period[49,50]. At 2.3 ± 1.1 years (2621 PY), Watchman device continued to be non-inferior to warfarin therapy with 3% and 4.3% event rates of primary efficacy endpoint for Watchman and warfarin groups, respectively. The second trial with 3.8 ± 1.7 years of follow up (2621 PY) showed event rate of 2.3% in the watchman group and 3.8% in the warfarin group (P = 0.0348), leading to 40% risk reduction in primary efficacy endpoint with Watchman device.
PREVAIL study (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy) was another randomized trial that assessed the safety and efficacy of Watchman device in patients non-valvular AF. Investigators included a higher risk patients than PROTECT AF (CHADS2 score of 1 plus any of the following higher-risk characteristics: female age ≥ 75 years, baseline ejection fraction ≥ 30% but < 35%, age 65 to 74 years and either diabetes or coronary disease, and age ≥ 65 years with congestive heart failure). Patients were assigned randomly to receive LAAO using Watchman (n = 269) or warfarin therapy (n = 138) in 2:l ratio. Warfarin and antiplatelet therapy post device implantion was in a similar fashion to PROTECT AF trial. Although non-inferiority criteria was not achieved for overall efficacy endpoint (stroke, systemic embolization or cardiovascualr death), the rate of second efficacy endpoint (stroke or systemic embolization) was 2.5% in the Watchman group and 2% in the warfarin group at 18 mo follow-up, achieving criteria for non-inferiority. Compared to PROTECT AF study, procedural success increased from 90.9% to 95.1% (P = 0.04), while all 7-d procedure-related complications (composite of cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, and other vascular complications) decreased from 8.7% to 4.2% in PREVAIL (P = 0.004).
PROTECT AF and PREVAIL results were pooled for patient level meta-analysis and with combined follow-up of 5 years (4343 PY). The primary efficacy endpoint (stroke, systemic embolization or cardiovascualr death) was similar between LAAO and warfarin groups (2.8 vs 3.4 events/100 PY; P = 0.27). In subgroup analysis of the same meta-analysis, the rate of all stroke or systemic embolism was similar between both groups (1.7 vs 1.8 events/100 PY; P = 0.87). However, there was statistically significant decrease in the rates of hemorrhagic stroke (0.17% vs 0.87%, P = 0.002), disabling / fatal stroke (0.37% vs 0.94%, P = 0.027), cardiovascular/unexplained death (1.3% vs 2.2%, P = 0.027), all-cause death (3.6% vs 4.9%, P = 0.035), and post-procedure bleeding (1.7% vs 3.6%, P = 0.0003) in LAAO arm when compared with warfarin arm. This meta-analysis underscores the mortality reduction and stroke prevention, patrticularly hemorrhagic stroke, associated with LAAO using Wathcman device.
Continued Access to PROTECT AF (CAP) and Continued Access to PREVAIL (CAP2) Registries were designed to treat patients with similar baseline characteristics and according to same protocols after PROTECT AF and PREVAIL trials enrollment had been completed. Procedural performance and associated medications were identical in each registry. However, registries did not mandate 1-year neurological assessment. A Meta-analysis of 2406 patients from the PROTECT AF and PREVAIL trials and their respective registries (CAP and CAP2) with 5,931 PY of follow-up (mean of 2.69 years) reported: similar rate of all-cause stroke between both arms (1.75 vs 1.87 events/100 PY, P = 0.94): higher rate of ischemic stroke in Watchman group (1.6 vs 0.9 events/100 PY, P = 0.05); and lower rates of hemorrhagic stroke, cardiovascular death (1.1 vs 2.3 events/100 PY, P = 0.006), and non-procedural bleeding (6.0% vs 11.3%, P = 0.02) in Watchman group. Although the rate of all-cause stroke was similar between both arms, the reduction in hemorrhagic stroke with Watchman device was balanced by a relative increase in ischemic stroke rates. This may relate to possible technical failures of the device: failure to completely obliterate LAA flow, anatomical remodeling of the LAA ostium over time resulting in more leaks, or the development of thrombus on the device. Compared with the pooled results of PROTECT AF and PREVAIL trials mentioned above, the difference in ischemic stroke rate was not observed between LAAO and warfarin groups at longer and combined follow-up of 5 years.
EWOLUTION study (Registry on Watchman Outcomes in Real-Life Utilization) is a multicenter, prospective, non-randomized cohort that aimed to collect peri-procedural and long-term outcome data for patients implanted with Watchman device for LAAO. This world-wide registry enrolled 1025 patients at 47 centers from the United States, Europe, Middle east and Russia who are more than 18-year-old and require LAAO based on ESC guidelines[55-57]. The device was successfully implanted in 98.5% and complete LAAO was achieved in 99.3% noted on TEE[56,57]. the rates of procedure-related serious adverse events (defined as; perforation, tamponade, embolism, neurological events, thrombosis, and bleeding) were 2.8% at 7 d and 3.6% at 30 d with bleeding being the most common adverse event. This is lower than the 7-d procedure-related serious adverse events observed in PROTECT AF (8.7%) and PREVAIL (4.2%) trials. At 1 year follow up; mortality was 9.8%, device-related thrombus was seen in 3.7% of patients, and 1.1% of patients suffered from ischemic stroke, leading to 84% risk reduction of stroke. There was no hemorrhagic stroke observed during follow-up.
The ASAP study (ASA Plavix Feasibility Study with Watchman LAA Closure Technology Trial to assess) was a European multicenter, prospective, non-randomized study of Watchman device in patients with non-valvular AF who had CHADS2 score ≥1 and were not eligible for OACs. After the device implantation, participants were given thienopyridine antiplatelet agent (clopidogrel or ticlopidine) for 6 mo and aspirin indefinitely. Out of 150 patients, 142 (94.7%) had successful implantation and 13 (8.7%) developed device-related adverse event. During mean follow up of 14.4 ± 8.6 mo, 4 patients developed stokes (2.3% per year) and 3 of them were ischemic (1.7% per year). There was 77% risk reduction in stroke compared to expected stroke risk based on CHADS2 score (7.3% per year). Till this moment, there is no published randomized data on the safety and efficacy of LAAO in patients with contraindications to anticoagulation. The ASAP TOO study (The Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is ongoing multi-center prospective randomized trial plan is to enroll up to 888 patients with non-valvular AF who are not candidate for OAC and have CHA2DS2-VASC ≥ 2. The study will randomize patients to Watchman vs control. Control patients will be prescribed single antiplatelet therapy, or no therapy based on physician discretion.
Amplatzer cardiac plug and amulet
Amplatzer cardiac plug (ACP) (AGA, St. Jude Medical, Minneapolis, MN, United States) is another LAAO device that consists of a lobe and disc made of nitinol mesh and polyester patch, connected by central waist. Amulet® is a second-generation device of the Amplatzer with several incremental design improvements. It is larger in size and has higher number of stabilizing wires, which allows successful closure of more LAA anatomies (Table 1). Comparative studies have shown similar results with ACP and Amulet AMPLATZER devices in terms of safety, implantation success and appropriate LAAO[60,61]. Multiple retrospective and prospective studies for ACP and Amulet reported successful device implantation in 95% to 100% patients, with major periprocedural adverse events (death, stroke/TIA, device embolization, MI/perforation/tamponade/effusion, and major bleeding) ranging from 3.2% to 8%[62-67]. An FDA approval trial is currently ongoing, with the aim of collecting randomized controlled data from the Amulet and Watchman devices from 1,600 patients worldwide. PRAGUE 17 is another ongoing prospective, multicenter, randomized trial That plan to enroll 396 patients with non-valvular AF and assign them to LAAO using Amulet or Watchman vs non-vitamin K oral anticoagulants (NOACs). The aim at 24 mo of follow-up is to determine whether LAAO is non-inferior to NOACs in terms of primary efficacy endpoint and peri-procedural complications.