Reviewer : Dr. Mustafa Yılmaztepe

Name  of  the  Study:  Amplatzer^™  Amulet^™  Left  Atrial  Appendage  Occluder  Versus Watchman^™ Device For Stroke Prophylaxis (Amulet IDE): A Randomized Controlled Trial

Published Congress: ESC 2021

Link: https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.121.057063

Background:

Patients with atrial fibrillation are at increased risk of ischemic stroke due to left atrial blood stasis that cause left atrial appendage thrombus formation. Life-long oral anticoagulation treatment is given to prevent thromboembolic events with a cost of increased risk of bleeding. Percutaneous  left  atrial  appendage  occlusion  (LAAO)  is  an  alternative  way  of  treatment  for preventing  thromboembolism,  particularly  in  patients  with  contraindication  to  long-term anticoagulation.  Watchman^™  Device  is  an  FDA  approved  LAAO,  it  has  a  single  seal mechanism  and  requires 6  weeks  of  post-procedural  oral  anticoagulation  treatment. Amplatzer^™ Amulet^™ LAAO is a new generation device with  dual-seal mechanism , which claims improved sealing of the LAA ostium and reduced risk of leak and additionally it does not require  post-procedural oral anticogaulation.

Objective:

The  purpose  of  this  study  is  to  compare  Amulet  occluder  to  Watchman  device  in  regard  to succesful LAA occlusion as well as safety and effectiveness for stroke prevention.

Methods:

This is a multi-center open label, randomized, controlled trial. A total of 1878 patients with non-valvular atrial fibrillation and at increased risk of stroke (CHADS2 score > 2 or CHAD2-VASc score > 3) were enrolled to the study and randomized 1:1 ratio to undergo percutaneous LAAO with  Amulet  occlluder  (934)  or  Watchman  device  (944).  Primary  safety  end-point  is  a composite of procedure related complications, all cause, death or major bleeding, through 12 months.  The  primary  effectiveness  end  point  is  a  composite  of  ischemic  stroke  or thromembolism  at  18  months  and  the  primary  mechanism  of  action  end  point  is  successful device  based  LAAO  (residual  jet  around  the  device  <  5mm)  at  45  day  visit.  Pre-specified secondary   endpoints   includes   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:

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).

Conclusion:

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.

Interpretations:

Although  the  rate  of  major  bleedings  were  similar  between  groups,  the  ability  to  discharge patients without oral antiplatelet therapy in the Amulet occluder group is a big step forward for the patients with contraindications to even short term oral anticoagulant treatment.  Since LAA may have different shapes and anatomical variations, having devices with different designs is a great chance. Having options makes pre-procedural planning and imaging more important to choose the best device for the patient.