Abbott's Amplatzer Amulet provided superior left atrial appendage (LAA) closure over the old-guard Watchman (Boston Scientific) device but failed to significantly cut stroke or bleeding rates in patients with atrial fibrillation, despite theoretical advantages in its design and the ability to forgo post-implant oral anticoagulation.
Oral anticoagulation (OAC) at discharge fell from 96% with the Watchman to 21% with the Amulet, but there was no significant difference in major bleeding between groups at 18 months (11.6% Amulet vs 12.3% Watchman).
The primary effectiveness endpoint of ischemic stroke or systemic embolism occurred in 2.8% of patients in each group at 18 months (P for noninferiority < .001).
Procedure-related complications were higher with the Amulet device, driven primarily by pericardial effusions (2.4% vs 1.2%) and device embolization (0.7% vs 0.2%).
Procedural complications were more common in early cases, likely reflecting a learning curve as the AMULET IDE trial was the first experience for many US implanters, observed principal investigator Dhanunjaya Lakkireddy, MD, Kansas City Heart Rhythm Institute, Overland Park, Kansas. "Once the operator hits a mark of seven procedures, this rate comes down and levels off thereafter."
Results of the first head-to-head comparison supported the August 14 federal approval of the Amulet for stroke prevention in atrial fibrillation and were reported in a Hot Line session today at the virtual European Society of Cardiology Congress 2021.
The device uses dual-seal technology to fill and close off the LAA and is available in more than 80 countries, including CE mark approval in Europe in 2013.
Designated discussant Gerhard Hindricks, MD, a co-author of the updated 2020 expert consensus statement on catheter-based left atrial appendage occlusion, congratulated the investigators on executing the largest LAAO trial thus far and said it is important because it "brings solid data to a field where data are really lacking."
He pointed out that the study used the older version of the single-occlusive Watchman device (approved in the US in 2015) but enrolled a high-risk patient population.
The ability to use dual-antiplatelet therapy (DAPT) in these patients with the dual-occlusive Amulet device, he said, "I think procedure-wise and also from the patient perspective, it's a significant step forward."
The Amulet IDE trial randomly assigned 1878 patients with nonvalvular AF to LAAO with the Amulet or Watchman based on preprocedural imaging at 78 US centers and 30 centers outside the US. Patients were discharged on aspirin or clopidogrel DAPT or aspirin plus oral anticoagulation if treated with the Amulet and aspirin with or without warfarin, as mandated for the Watchman.
The population had an average age of 75 years, a CHA2DS2-VASc score of 4.5 to 4.7 and HAS-BLED score of about 3.2. Nearly three fourths had a history of minor or major bleeding.
The implant was successful in 98.4% of the 915 Amulet patients and in 96.4% of the 916 Watchman patients.
The primary endpoint of LAA closure, defined as a residual jet of 5 mm or less at 45 days, was achieved in 98.9% of patients with the Amplatzer and 96.8% with the Watchman (P for superiority = .0025).
A residual jet of 3 mm or less was more common with the Amplatzer (89.8% vs 75.1%; P for superiority < .0001).
"The 2% difference in a residual jet of 5 mm was statistically significant in favor of the dual-occlusive device; however, the clinical relevance of this small difference, at the end of the day, is unclear whether that relates to any type of complications during follow-up," said Hindricks, from the Heart Center of Leipzig, Germany.
The Amulet met noninferiority for the primary composite safety endpoint of procedure-related complications, all-cause death, or major bleeding through 12 months (14.5% Amulet vs 14.7% Watchman; P = .0002).
Rates for procedure-related complications were 4.5% with Amulet and 2.5% with Watchman, 3.9% Amulet vs 5.1% Watchman for all-cause death, and 10.6% Amulet vs 10% Watchman for type 3 or higher major bleeding.
Panelist Renato D. Lopes, MD, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina, agreed the trial represents a major step for the field and provides clinicians with another tool, but said a 10%–12% bleeding rate is high, particularly in elderly patients, compared with other novel OAC trials, albeit generally enrolling lower-risk patients.
"The way I see it, when we choose a treatment for these patients, we really want to minimize bleeding and preserve the efficacy so we can find the sweet spot, but if the bleeding risk here seems to be high, how can we incorporate it in practice?" Lopes said.
Lakkireddy said the study subselected a population at high risk for bleeding and that he wasn't actually surprised that bleeding rates were at 10% because prior data have shown DAPT doesn't completely eliminate bleeding.
"In fact, the bleeding is perhaps as much as oral anticoagulation and that is the reason why, I believe, our secondary endpoint was not much different from the Amulet DAPT and Watchman Coumadin patients," he said.
Lakkireddy pointed out that the Watchman group stopped oral anticoagulation at 6 weeks and then switched to aspirin plus clopidogrel for up to 6 months before continuing on single-antiplatelet therapy.An analysis is planned, he said, to "dive deeper into this bleeding issue to see if the bleeding complications are all congregated in the first 45 days in the postprocedure period or were seen throughout follow-up for the 12-month safety endpoint."
Marco Valgimigli, MD, Cardiocentro Ticino Foundation, Lugano, Switzerland, asked whether DAPT would have looked different if the Watchman FLX had been used as the comparator.
The Pinnacle FLX trial showed that there's a high rate of closure with the newer iteration but that randomized trials are lacking, and that in cases with, for example, very large ostia or very proximal lobes with a vertical takeoff, "a Watchman device is simply not a great fit," Lakkireddy said.
"This is where, I think, the dual-occlusive mechanism occluders really shine because you can insert the lobe deeper in and then the outer disk beautifully covers the ostium, giving you the coverage that you need without leaving behind the proximal lobes or other things and, as a result of which, you have a much better closure," he said.
Now that both devices are available in the US, Lakkireddy said the use of imaging, preferably CT, becomes even more relevant to select the best device preoperatively.
Speaking with theheart.org | Medscape Cardiology, Lakkireddy said a cost-effectiveness analysis is planned but that current data already clearly show LAAO closure is a better financial proposition in the long run.
"When you look at the cost of using a DOAC and if you take into consideration the cost of treating bleeding and strokes, by 3.5 years the curves cross over and the left atrial appendage [closure] actually makes more sense," he said. "And atrial fibrillation being a chronic disease, I think that's a major win and something we have to take into consideration."
The trial was funded by Abbott. Lakkireddy discloses serving on a speaker's bureau for Boston Scientific, Biosense Webster, and Janssen Pharmaceuticals; and receiving honoraria or speaking or consulting fees from Abbott, Stereotaxis, and Atricure.
European Society of Cardiology (ESC) Congress 2021. Presented August 30, 2021.
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Cite this: Amulet Bests Watchman for LAAO But Not for Bleeding: AMULET-IDE - Medscape - Aug 30, 2021.