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Amulet IDE

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

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Year of Publication: 2021

Authors: Dhanunjaya Lakkireddy, David Thaler, Christopher R. Ellis, ..., Stephan Windecker

Journal: Circulation

Citation: Circulation. 2021;144:1543–1552. DOI: 10.1161/CIRCULATIONAHA.121.057063

Link: https://www.ahajournals.org/journal/circ

Clinical Question

Is the dual-seal mechanism Amulet LAA occluder noninferior to the single-seal Watchman device for safety and effectiveness in stroke prevention for patients with nonvalvular atrial fibrillation?

Bottom Line

The Amulet occluder was noninferior to the Watchman device for safety and effectiveness endpoints and superior for LAA occlusion rates, but had higher procedure-related complications that decreased with operator experience.

Major Points

  • First large-scale randomized trial comparing different LAA occlusion devices
  • Dual-seal mechanism (Amulet) versus single-seal mechanism (Watchman)
  • 1878 patients randomized 1:1 at 108 sites across US and international centers
  • Met all three primary endpoints for noninferiority in safety and effectiveness
  • Superior LAA occlusion with Amulet (98.9% vs 96.8%)
  • Higher procedural complications with Amulet, especially early in operator experience
  • Similar rates of ischemic stroke, major bleeding, and device-related thrombosis

Design

Study Type: Multicenter, open-label, randomized controlled trial

Randomization: 1

Blinding: Independent clinical events committee blinded to treatment assignment; echocardiographic core laboratory not blinded

Enrollment Period: September 2016 through March 2019

Follow-up Duration: 18 months

Centers: 108

Countries: United States, Denmark, Germany, Switzerland

Sample Size: 1878

Analysis: Intention-to-treat for effectiveness, per-protocol for safety; Kaplan-Meier method with Greenwood formula; Cox regression model; logistic regression; SAS software version 9.4

Inclusion Criteria

  • ≥18 years of age
  • Documented paroxysmal, persistent, or permanent nonvalvular atrial fibrillation
  • Increased risk of stroke or systemic embolism (CHADS2 score ≥2 or CHA2DS2-VASc score ≥3)
  • Suitable LAA anatomy for implanting both devices on TEE screening
  • Suitable for anticoagulation therapy for 6 months
  • Appropriate rationale to seek nonpharmacological alternative to oral anticoagulation

Exclusion Criteria

  • Unsuitable LAA anatomy for one or both devices
  • Various procedural contraindications
  • Recent stroke or bleeding events
  • Other cardiac conditions precluding procedure

Arms

FieldControlAmulet Occluder
InterventionPercutaneous implantation of Watchman LAA occluder with single-seal mechanism, followed by aspirin plus warfarin for 6 weeks, then aspirin plus clopidogrel until 6 months, then aspirin indefinitelyPercutaneous implantation of Amulet LAA occluder with dual-seal mechanism (lobe and disc), discharged on aspirin plus clopidogrel or aspirin plus OAC at investigator discretion
DurationPermanent device implant with variable anticoagulation durationPermanent device implant with variable anticoagulation duration

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Composite safety endpoint: procedure-related complications, all-cause death, or major bleeding at 12 monthsPrimary14.7%14.5%0.20%<0.001 for noninferiority
Primary effectiveness: ischemic stroke or systemic embolism at 18 monthsSecondary2.8%2.8%<0.001 for noninferiority
LAA occlusion (residual jet ≤5mm) at 45 daysSecondary96.8%98.9%0.003 for superiority
Stroke, systemic embolism, or cardiovascular/unexplained death at 18 monthsSecondary7.7%5.6%<0.001 for noninferiority
Major bleeding at 18 monthsSecondary12.3%11.6%0.32 for superiority
Procedure-related complicationsAdverse2.5%4.5%1.86 (1.11 to 3.12)0.02
All-cause deathAdverse5.1%3.9%0.76 (0.49 to 1.19)0.23
Device-related thrombosisAdverse4.5%3.3%
Pericardial effusionAdverseLower frequencyHigher frequency
Device embolizationAdverseLower frequencyHigher frequency

Subgroup Analysis

Prespecified subgroup analyses showed no evidence that differences in results between groups were different across subgroup strata for any primary endpoints

Criticisms

  • Open-label design with no blinding of investigators or patients
  • High number of patients excluded due to unsuitable anatomy, limiting generalizability
  • Echocardiographic core laboratory was not blinded
  • Comparison with first-generation Watchman device rather than newer Watchman FLX
  • US sites had no previous Amulet experience, potentially contributing to higher complication rates
  • Unknown optimal antithrombotic regimen for best stroke/bleeding risk balance
  • Higher late pericardial effusion rates in Amulet patients on OAC needs further study
  • Death as competing risk for primary efficacy endpoint not accounted for in time-to-event analyses

Funding

Abbott

Based on: Amulet IDE (Circulation, 2021)

Authors: Dhanunjaya Lakkireddy, David Thaler, Christopher R. Ellis, ..., Stephan Windecker

Citation: Circulation. 2021;144:1543–1552. DOI: 10.1161/CIRCULATIONAHA.121.057063

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