From November 4th to November 6th, 2021, the American Conference on Transcatheter Cardiovascular Therapy (TCT 2021), which returned in a unique way, has won the attention of cardiovascular professionals worldwide. The unlocking of multiple hot research topics is stirring every nerve of those who pay attention. In the highly anticipated eyes of people, dozens of studies on left atrial appendage occlusion have become one of the most eye-catching highlights. The excellent academic reports on PRAGUE-17, AMULET IDE, and SWISS-APERO presented during the conference have sparked heated discussions among scholars at home and abroad. These three heavyweight studies not only represent the latest cutting-edge advances in different research directions in the field of left atrial appendage occlusion, but also further validate the feasibility and effectiveness of left atrial appendage occlusion technology. At the same time, they demonstrate the unique charm of WATCHAMN and WATCHAMN FLX occluders through the head to head comparison of cap occluders and plug occluders!
PRAGUE-17 study 3-year follow-up: LAAC is not inferior to NOAC in preventing atrial fibrillation stroke and has a greater advantage in reducing bleeding events
TCT2021 ONLINE
Research Design: PRAGUE-17 is a prospective, multicenter, non blinded, randomized, non inferiority trial initiated by researchers to compare the role of LAAC and NOAC in stroke prevention in patients with atrial fibrillation. Researchers enrolled 415 patients with non valvular atrial fibrillation from 10 heart centers in the Czech Republic and randomly divided them into LAAC group (201 cases) and NOAC group (201 cases) in a 1:1 ratio. The primary endpoint is a composite event that includes stroke/TIA, systemic embolism, clinically relevant bleeding, cardiovascular death, perioperative or instrument related major complications (Figure 1); The main analysis method is intention to treat analysis.
Figure 1. Experimental Design Process
Research results/conclusions: After a median follow-up of 3.5 years (1354 patient years), the LAAC group was not inferior to the NOAC group in terms of cumulative incidence of primary endpoint events (8.6% vs. 11.9%, sHR=0.81, 95% CI 0.56-1.18; P=0.27, non inferiority P-value=0.006) (Figure 2). The incidence of cardiovascular death (sHR=0.68, 95% CI 0.39-1.20, P=0.19) and all-cause stroke/TIA events (sHR=1.14, 95% CI 0.56-2.30, P=0.72) were similar between the two groups. It should be noted that the incidence of clinically relevant bleeding in the LAAC group was lower than that in the NOAC group, with no statistical difference (sHR=0.75, 95% CI 0.44-1.27, P=0.28); In terms of non clinically relevant bleeding events, the incidence of LAAC group was not only lower than that of NOAC group, but also had statistical differences (3.4% vs. 5.9%, sHR=0.55, P=0.038) (Figure 3). According to the long-term follow-up results mentioned above, LAAC is not inferior to NOAC in preventing major cardiovascular and neurological events in high-risk stroke patients with NVAF. At the same time, the significant reduction in the incidence of non-surgical bleeding events highlights the advantages of LAAC in reducing bleeding, once again demonstrating the key advantages that LAAC technology can bring to atrial fibrillation patients, suggesting that it can be used as a non pharmacological alternative to long-term anticoagulation in NVAF patients.
Figure 2. Primary endpoint event incidence rate
Figure 3. Incidence of clinically related bleeding and non-surgical clinically related bleeding
12-month follow-up of AMULETIDE study: The method of detecting residual shunt with occluder and the advantages of occluder still need to be demonstrated
TCT2021 ONLINE
Research Design: AMULET IDE is a prospective, multicenter, randomized controlled study initiated in September 2016. A total of 1878 stroke high-risk (CHADS2 score ≥ 2 or CHA2DS2 VASc score ≥ 3) non valvular atrial fibrillation patients from 150 centers worldwide were enrolled and randomly divided into the Amulet occluder group (903 cases) and WATCHMAN occluder group (885 cases) in a 1:1 ratio. The aim was to evaluate the safety and effectiveness of the Amulet occluder in preventing atrial fibrillation stroke by comparing it head to head with the plug WATCHMAN occluder. The primary safety endpoint is a composite endpoint consisting of 12-month surgical related complications, all-cause mortality, or major bleeding. Primary efficacy endpoint: Ischemic stroke or systemic embolic events within 18 months (Figure 4).
Figure 4. Experimental Design Process
Research findings/conclusions: Based on previously published data, the use of Amulet and WATCHMAN in LAAC achieved non inferiority endpoints in terms of efficacy endpoints, with no significant difference between the two, once again proving the effectiveness of left atrial appendage occlusion in patients with atrial fibrillation. In terms of the primary safety endpoint, the 12-month follow-up of Amulet also achieved non inferiority, but the incidence of surgical related complications in patients implanted with Amulet occluders was nearly twice that of the WATCHMAN group, reflecting the safety of using WATCHMAN for LAAC surgery. In addition, in addition to the efficacy and safety endpoints mentioned above, this study also established a device operation endpoint of evaluating the closure rate of the occluder by detecting residual shunt around the occluder through TEE; Based on the 45 day follow-up results, Amulet is superior to WATCHMAN occluder in terms of occlusion effectiveness, with a relatively lower incidence of residual shunt. However, Professor Saibal Kar also expressed his views during the discussion session: 1. The study only used TEE to evaluate PDL, which may underestimate the incidence of residual shunt in occluders. CT can detect more residual shunt in occluders; 2. Previous randomized and registered studies have not found any association between residual shunt and thrombosis or MACE events; 3. If Amulet is compared with WATCHMAN FLX, the results will be completely different, because in the PINNACLE study, the effective occlusion rate of WATCHMAN FLX reached 100%. Therefore, it remains to be demonstrated whether the reduction of residual shunt is sufficient to become the advantage of a covered occluder. Taking all factors into consideration, although the current study has shown that Amulet is not inferior to WATCHMAN, further clinical research is still needed to provide more evidence to truly validate this viewpoint.
SWISS-APERO trial: Amulet occlusion is not superior to WATCHMAN 2.5/FLX occluder, and the incidence of surgical complications is higher
TCT2021 ONLINE
Research Design: SWISS-APERO is an open label, multicenter, randomized superiority clinical trial initiated by researchers. From September 19, 2018 to May 18, 2021, a total of 221 non valvular AF patients with LAAC clinical indications from 4 countries and 8 centers were enrolled. They were randomly divided into the Amulet group (111 cases) and WATCHMAN2.5/FLX group (110 cases; 22.7% WATCHMAN2.5, 77.3% WATCHMAN FLX) in a 1:1 ratio. It is the world's first multicenter randomized controlled trial to compare the sealing performance, surgical complications, and short-term clinical outcomes of Amulet and WATCHMAN/WATCHMAN FLX. The sentence is:. The primary endpoint is a composite event that includes "justified crossover to the non randomly allocated device" and the 45 day left atrial appendage (LAA) contrast agent patent rate assessed by CCTA. Among them, reasonable crossover is defined as the selection of non randomly assigned instruments for implantation due to morphological/anatomical considerations after at least one attempt to implant the specified occlusion instrument; If the LAA density is ≥ 100 HU or ≥ 25% of the LA density, LAA is defined as contrast agent penetration (PA). In PA patients with visible shunt, if contrast agent passes through the device, it is classified as intra device shunt (IDL); If both are classified as PDL at the edge of the device, it is called Mixed Split Flow (MIL). If none of the above situations are present, it can be determined that there is no visible shunt in PA (PANVL) (Figure 5).
Figure 5. Classification criteria for PA and non PA patients
Research results: One patient in the Amulet group switched to the WATCHMAN group due to multiple attempts during surgery and an unsuitable anatomical structure of the left atrial appendage, while two patients interrupted surgery due to severe cardiac tamponade during surgery. The 45 day CCTA follow-up results showed that a total of 71 patients (67.6%) in the Amulet group experienced the primary endpoint event, while 70 patients (70.0%) in the WATCHMAN group; It can be seen that in terms of sealing, the use of Amulet during LAAC surgery is not superior to WATCHMAN (RR 0.97; 95% CI 0.80-1.16; P=0.713). However, there are differences in the mechanism of PA occurrence between the two groups. Firstly, on PANVL (no visible shunt), the WATCHMAN group was more common (21.0% vs. 9.5%; P=0.022), while internal shunt within the instrument was more common in the Amulet group (44.8% vs. 23.0%; P=0.001) (Figure 6). There was no statistically significant difference in shunt around the instrument between the two groups. Further analysis showed that in terms of safety endpoints, patients implanted with Amulet devices had a significantly higher incidence of severe surgical related complications compared to the WATCHMAN group (9.0% vs. 2.7%; P=0.047), mainly reflected in more major bleeding events (7.2% vs. 1.8%; P=0.054) and more clinically relevant pericardial effusion (3.6% vs. 0.0%; P=0.122) in the Amulet group. (Figure 7). In addition, there were 2 deaths, 2 cerebrovascular events, 2 air embolism, and 1 systemic embolism in the Amulet group, but no similar events occurred in the WATCHMAN group. In terms of 45 day clinical events, the incidence of composite events was similar between the two groups, but the Amulet group had more newly developed pericardial effusion (19.8% vs. 7.3%; P=0.006). This study once again confirms the good safety and sealing of WATCHMAN/WATCHMAN FLX.
Figure 6. Incidence of primary endpoint events and distribution of PA types between the two groups
Figure 7. Incidence of major surgical complications and 45 day clinical outcomes
summary
TCT2021 ONLINE
After nearly 20 years of development, LAAC, as an important treatment method to reduce the incidence rate of atrial fibrillation stroke, has shown great efficacy and attraction to clinicians and patients. After TCT 2021, the longer-term follow-up data of PRAGUE-17 and AMULET IDE studies have been officially revealed, and the 45 day follow-up data of the world's first multicenter randomized controlled trial of Amulet and WATCHMAN FLX have also been presented. These research data provide very meaningful scientific basis for the clinical application of left atrial appendage occlusion, especially WATCHAMN left atrial appendage occlusion device. On this basis, we believe that with the continuous emergence of key breakthroughs in evidence-based medicine, scientific problem exploration, device evolution and innovation, LAAC technology will demonstrate more vitality and resilience. In this process, the unique advantages of WATCHAMN/WATCHAMNFLX occluder will also win recognition from more clinical physicians and patients.