Amulet IDE: a new left atrial appendage occlusion device enters the market for patients with atrial fibrillation and contraindications to anticoagulation.

By Enrico G. Ferro, MD on

Key points:

• The Amulet IDE is an open-label clinical trial that randomized 1,878 patients with non-valvular atrial fibrillation to receive either the novel Amulet device or the first-generation Watchman device, to compare the efficacy and safety of the two percutaneous left atrial appendage occlusion (LAAO) devices.

• The Amulet device was found to be superior to first-generation Watchman in effectively occluding the LAA (residual jet ≤5 mm at 45 days, 98.9% vs 96-8%, p=0.0025) and non-inferior with regard to procedure-related complications, major bleeding or all-cause death at 12 months (safety), and ischemic stroke or systemic embolism at 18 months (efficacy).

• Despite the difference in antithrombotic regimens used with the two devices (aspirin + warfarin for Watchman, versus aspirin + clopidogrel or aspirin + direct oral anticoagulant for Amulet), both the rates of bleeding and device-related thrombus were similar in the two arms.

• On August 14th, 2021, the Amulet percutaneous LAAO device received FDA approval.

Patients with atrial fibrillation (AF) may have a variety of relative or absolute contraindications to long-term anticoagulation, leaving them exposed to the risk of stroke. This is particularly relevant for elderly patients, who may both have a higher bleeding risk and face a higher annual risk of stroke, which on average increases from 1.5% in individuals aged 50–59 years to 23.5% for those aged 80–89 years. Based of echocardiography and autopsy studies, the left atrial appendage (LAA) has been identified as a key source of thromboembolism in more than 90% of patients with non-valvular AF. The recent LAAOS III trial further demonstrated that surgical LAA occlusion (LAAO) was superior to no occlusion in reducing thromboembolism among patients with AF who were undergoing cardiac surgery; most importantly, this benefit was additive to anticoagulation, since over 75% of patients in both arm remained on long-term anticoagulation therapy. This data explains the growing interest in developing percutaneous catheter-based devices to effectively exclude the LAA from the systemic circulation. Starting in 2015, the Watchman device was the first percutaneous LAAO device to obtain FDA approval as an innovative stroke prevention option for patients with high-bleeding risk.

Dr. Dhanunjaya Lakkireddy, MD from the Kansas City Heart Rhythm Institute at HCA Midwest Health presented the results for a new percutaneous LAAO device, which was just granted FDA approval on August 14th, 2021. The findings were presented on August 30th, 2021 at the annual European Society of Cardiology (ESC) Congress. In the Amulet IDE open-label, randomized clinical trial, 1,878 patients (1,598 from 78 U.S. centers, and 280 from 30 centers outside the US) were randomized 1:1 to receive either the novel Amulet device, or the first-generation Watchman device. Eligibility criteria included non-valvular AF, high stroke risk (CHA2DS2-VASc score ≥3), being suitable for short-term warfarin but with an appropriate rationale to seek an alternative to anticoagulation therapy, and being suitable for LAA closure. The primary non-inferiority composite endpoint included mechanism of action (residual LAA jet around the device ≤5mm at 45 days), safety (procedure-related complications, major bleeding or all-cause death at 12 months), and effectiveness (ischemic stroke or systemic embolism at 18 months). Secondary endpoints included testing for superiority for each of the individual endpoints, as well as for major bleeding. Importantly, per protocol, patients treated with first-generation Watchman devices were mandated to remain on aspirin plus warfarin, while patients treated with Amulet could be treated with aspirin + clopidogrel or aspirin + direct oral anticoagulant.

A total of 934 Amulet and 944 Watchman devices were deployed, with 30 unsuccessful implants in the Watchman arm and 6 in the Amulet arm due to unsuitable patient anatomy. There were no significant difference in patient baseline characteristics, and over 90% of patients completed their last follow-up evaluation at 18 months. With regard to the primary endpoints, the Amulet device was found to be superior to first-generation Watchman in effectively occluding the LAAO (residual jet ≤5 mm at 45 days, 98.9% vs 96-8%, p=0.0025) and non-inferior for safety and efficacy. With regards to safety, complications such as pericardial effusion were numerically higher in the Amulet arm compared to the Watchman arm (2.4% vs 1.2%), though they decreased with increased operator experience (of note, this trial represented the first experience with the Amulet device for U.S. operators). With regard to efficacy, the risk of ischemic stroke or systemic embolism was identical for the two devices (2.8%) at 18 months. Notably, despite the difference in antithrombotic regimens between the two arms, the rate of device related thrombus (DRT) was also similar (3.3% with Amulet and 4.5% with first-generation Watchman). In addition, despite the difference in antithrombotic regimens, the rate of major bleeding was similar in the two arms (10.6% in Amulet vs 10.0% in Watchman).

In conclusion, the Amulet device joins the Watchman devices as an alternative for LAA exclusion among patients with AF who are not eligible or have an appropriate rationale to avoid anticoagulation therapy. When selecting the most appropriate percutaneous option, one should also consider that the second-generation Watchman device (Watchman FLX) also received FDA approval in July 2020. While in the trial Amulet seemed to allow for more flexibility in the LAA anatomy that can be closed percutaneously, the Watchman FLX device also introduces a broader range of sizes that can match a wider range of patient anatomies – the two devices have not been tested head-to-head. In addition, the Amulet and Watchman FLX devices now require the same antithrombotic regimen (primarily dual anti-platelet therapy) – even though there was no significant difference in bleeding risk (or device-related thrombus) regardless of the antithrombotic regimen used in the trial.

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