Amplatzer Amulet Left Atrial Appendage Occluder Versus Watchman Device for Stroke Prophylaxis (Amulet IDE): A Randomized, Controlled Trial

Abstract

Background: Percutaneous closure of the left atrial appendage (LAA) is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with non-valvular atrial fibrillation (NVAF). The Amplatzer™ Amulet™ LAA Occluder IDE Trial (Amulet IDE Trial) was designed to evaluate the safety and effectiveness of the dual-seal mechanism of the Amulet LAA occluder compared with the Watchman™ device. Methods: Patients with NVAF at increased risk of stroke were randomly assigned (1:1) to undergo percutaneous implantation of a LAA occluder with the Amulet occluder or Watchman device. The primary endpoints included safety (composite of procedure-related complications, all-cause death, or major bleeding at 12 months) and effectiveness (composite of ischemic stroke or systemic embolism at 18 months) and the rate of LAA occlusion at 45 days. Pre-specified secondary endpoints included a composite of all stroke, systemic embolism, or cardiovascular/unexplained death at 18 months, major bleeding at 18 months, and superiority test of the three primary endpoints. Results: A total of 1878 patients were enrolled. The Amulet occluder was noninferior to the Watchman device for the primary safety endpoint (14.5% vs. 14.7%; difference=-0.14, 95% CI, -3.42-3.13; p<0.001 for noninferiority). Major bleeding and all-cause death were similar between groups (10.6% vs 10.0% and 3.9% vs 5.1%, respectively). Procedure-related complications were higher for the Amulet occluder (4.5% vs. 2.5%), largely related to more frequent pericardial effusion and device embolization. The Amulet occluder was noninferior to the Watchman device for the primary effectiveness endpoint (2.8% vs. 2.8%; difference=0.00, 95% CI, -1.55-1.55; p<0.001 for non-inferiority), and the composite of stroke, systemic embolism or cardiovascular/unexplained death (5.6% vs 7.7%, difference=-2.12, 95% CI, -4.45-0.21; p<0.001 for noninferiority). The rate of major bleeding was similar between groups (11.6% vs. 12.3%; difference=-0.71, 95% CI -3.72-2.31; p=0.32 for superiority). LAA occlusion was higher for the Amulet occluder compared with the Watchman device (98.9% vs. 96.8%; difference=2.03, 95% confidence interval [CI], 0.41-3.66; p<0.001 for noninferiority; p=0.003 for superiority). Conclusions: The Amulet occluder was non-inferior for safety and effectiveness of stroke prevention for NVAF compared with the Watchman device, and superior for LAA occlusion. Procedure-related complications were higher with the Amulet device and decreased with operator experience. Clinical Trial Registration: URL https://clinicaltrials.gov Unique Identifier NCT02879448

Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: Primary Results of the SWISS-APERO Randomized Clinical Trial

“…The recent Amulet IDE trial (AMPLATZER Amulet LAA Occluder Trial) was the first head-to-head randomized comparison of Amulet versus Watchman 2.5 and showed the superiority of the former over the latter in terms of LAA occlusion rate at 45-day TEE. 8 In March 2019, the second-generation Watchman FLX was released with design iterations aimed at improving LAA sealing and facilitating device implantation in complex LAA anatomies. No randomized clinical trial has so far compared the new Watchman FLX versus the Amulet in terms of residual LAA patency, rates of periprocedural complications, or short-term clinical outcomes.…”

Amulet™ Shines and Protects; Pacing Battle Intensifies with “More Leads or No Leads”?

“…It is available in 8 different sizes with a minimum LAA depth of 12 mm. 6,12 In comparison, the Watchman™ device is a self-expanding nitinol frame semi-covered by a polyethylene terephthalate membrane fabric held in by 10 anchors, while the Watchman™ FLX is fully covered by the membrane fabric with 12 anchors. 6,12 The Amulet IDE trial randomized 1,878 patients in an intention-to-treat analysis to either the Watchman™ 2.5 device or Amulet™ device.…”

“…6,12 In comparison, the Watchman™ device is a self-expanding nitinol frame semi-covered by a polyethylene terephthalate membrane fabric held in by 10 anchors, while the Watchman™ FLX is fully covered by the membrane fabric with 12 anchors. 6,12 The Amulet IDE trial randomized 1,878 patients in an intention-to-treat analysis to either the Watchman™ 2.5 device or Amulet™ device. The Amulet™ device was shown to be as effective as Watchman™ in the composite outcome of stroke, systemic embolism, or cardiovascular/unexplained death (5.6% vs. 7.7%; difference, −2.12; 95% confidence interval, −4.45 to 0.21; P < .001 for noninferiority).…”

Non-efficacy benefits and non-inferiority margins: a scoping review of contemporary high-impact non-inferiority trials in clinical cardiology

“…Non-efficacy benefits were most commonly (n = 23, 39%) related to anticoagulation strategies or comparing interventions that require different downstream anticoagulation strategies. Associated non-efficacy benefits included having to use less anticoagulants (with accompanying lower bleeding risk) or convenience to use anticoagulants without the need for therapeutic monitoring [ 5 – 8 , 14 , 17 , 21 , 22 , 24 , 28 , 32 , 33 , 36 , 40 , 41 , 44 , 48 , 58 , 62 , 63 ]. Another common non-efficacy benefit was the use of less invasive techniques to diagnose or treat a variety of cardiac conditions (n = 9, 15%) [ 19 , 21 , 23 , 25 – 27 , 42 , 45 , 54 ].…”