Amulet 360 Seals Better But Single-Arm Data Limits Approval Leverage

Abbott's Amulet 360™ Demonstrates High LAA Closure Rates in VERITAS Study

Abbott announced one-year results from its VERITAS study for the investigational Amulet 360™ Left Atrial Appendage (LAA) Occluder, a next-generation device designed to reduce stroke risk in patients with non-valvular atrial fibrillation. Presented at the Transcatheter Cardiovascular Therapeutics (TCT) conference and published in JACC: Cardiovascular Interventions, the data showed high rates of LAA closure and a low incidence of stroke. Specifically, 96.3% of patients achieved complete LAA closure, and over 98% remained free from ischemic stroke or systemic embolism through one year. The device aims to offer an alternative to long-term blood-thinning medication, leveraging enhanced design features for improved conformability and sealing across diverse LAA anatomies.

• Robust Efficacy in LAA Closure and Stroke Prevention: The VERITAS study demonstrated significant efficacy, with 96.3% of patients achieving complete left atrial appendage closure (zero mm leak) as evaluated by transesophageal echocardiography. Furthermore, over 98% of patients remained free from ischemic stroke or systemic embolism through one year, highlighting the device's effectiveness in preventing blood clot-related complications in non-valvular AFib patients.
• Strong Safety Profile Through One Year: The Amulet 360™ device exhibited a favorable safety profile, with more than 99% of patients free from pericardial effusion requiring intervention and over 98% free from cardiovascular-related mortality. Importantly, major bleeding events were not reported in 93.4% of patients during the first year of follow-up, underscoring its safety as an alternative to long-term oral anticoagulation.
• Advanced Device Design for Broader Patient Suitability: Amulet 360™ incorporates redesigned features, including a softer, more conformable lobe and an outer disc providing a second sealing layer. These enhancements allow the implant to adapt to a wider range of LAA anatomies, supporting durable closure and expanding treatment options for physicians. This next-generation design aims to improve clinical performance and patient outcomes by addressing diverse anatomical challenges.

Why Alternatives to Blood Thinners Are Needed for AFib

Current treatment for non-valvular atrial fibrillation remains constrained by efficacy-safety trade-offs, complex pharmacology, and real-world underuse. While oral anticoagulation is the cornerstone for preventing stroke and thromboembolism, limitations of both vitamin K antagonists and newer agents restrict optimal long-term management.

• Vitamin K antagonist pharmacologic and practical burden: Warfarin has slow onset and offset of action, narrow therapeutic window, marked dose-response variability, genetic variability in metabolism, multiple drug and food interactions, unpredictable anticoagulant effects, and require frequent coagulation monitoring and dose adjustments. Only 55% of eligible patients with AF received it, 28% of patients discontinue it by 1-year, rates of major bleeding are higher that 20% and patients remain in the therapeutic range (INR 2-3) only 58% of the time.

• Persistent under-prescribing in real-world practice: Oral anticoagulant therapy was prescribed in 54% of cases, above all in persistent or permanent forms, in patients with higher CHA2DS2-VASc score and younger age. Many high-risk AF patients are not offered guideline-recommended stroke prevention therapy due to a variety of system, provider, and patient-level barriers.

• Non-vitamin K antagonist oral anticoagulant dosing and monitoring gaps: Pharmacokinetic/pharmacodynamic data show the NOACs are dependent on renal clearance to varying extents, including dabigatran, apixaban, edoxaban, and rivaroxaban. Dosing recommendations differ depending on the NOAC, whereby some require dose reductions based solely on renal function while others require consideration of additional criteria, yet emerging real-world evidence suggests patients are not being dosed appropriately. Some issues remain unresolved, such as the lack of antidotes and standardized tests to measure drug activity.

• Left atrial appendage closure procedural and long-term risk: In 816 patients with mean follow-up of 16.0 ± 0.3 months, high TE (CHA DS -VASc score: 4.6 ± 0.1) and bleeding risks (HAS-BLED score: 3.2 ± 0.05) and common contraindications to long-term anticoagulation (95.7%), procedure or device-related serious adverse events occurred in 49 (6.0%) patients. The annual rate of ischemic stroke/systemic embolism was 3.3% (2.4-4.6), and the annual mortality rate was 10.2% (8.4-12.3), with most deaths due to comorbidities or underlying cardiovascular diseases.

VERITAS Study: Design and One-Year Amulet 360 Results

Key trials in non-valvular atrial fibrillation span double-blind pivotal comparisons of direct oral anticoagulants versus warfarin, as well as open-label strategy trials in specific settings such as acute ischaemic stroke, intracerebral haemorrhage survivorship, transcatheter valve replacement, and coronary intervention. Designs range from large phase 3 double-blind randomised trials to prospective observational cohorts and phase 4 strategy trials, with primary endpoints consistently built around stroke or systemic embolism and major bleeding.

Amulet 360's Place in the Evolving AFib Landscape

Factor XI inhibitors have been compared with direct oral anticoagulants in three randomized trials in patients with atrial fibrillation involving 16,852 patients. The PACIFIC-AF (Phase 2) and OCEANIC-AF (Phase 3) trials compared asundexian, an oral, small-molecule FXIa inhibitor, with apixaban, while AZALEA-TIMI 71 (Phase 2) compared abelacimab, a subcutaneous monoclonal antibody against FXI/FXIa, with rivaroxaban.

For bleeding, FXI inhibitors reduced the composite of International Society of Thrombosis and Haemostasis major bleeding or clinically relevant non-major bleeding (pooled-OR 0.39, 95%CI 0.30–0.50, p = 0.0005), major bleeding (OR 0.30, 95%CI 0.22–0.41, p = 0.004) and clinically relevant non-major bleeding (pooled-OR 0.44, 95% CI 0.36–0.55, p = 0.0004) compared to direct oral anticoagulants. Effects were consistent across sex, clinical risk factors and concomitant antiplatelet therapy. In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban, and abelacimab reduced major and clinically relevant nonmajor bleeding by 62% versus rivaroxaban. In PACIFIC-AF, asundexian reduced bleeding by 50%-84% compared to apixaban.

For thrombotic efficacy and mortality, exploratory analyses showed FXI inhibitor use was associated with greater risk of ischaemic stroke (OR 3.37, 95%CI 2.18–5.19, p = 0.001), similar rate of intracranial hemorrhage and lower all-cause mortality (OR 0.82, 95%CI 0.71–0.94, p = 0.02) than direct oral anticoagulants. OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination, and asundexian was inferior to apixaban for stroke prevention in atrial fibrillation. Abelacimab showed a trend toward higher ischemic stroke rates (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant.