Large Registry Study Suggests Amplatzer Plug Cuts Stroke, Bleeding Risks in A-fib
Left atrial appendage (LAA) closure using the Amplatzer cardiac plug is associated with lower than expected risks of systemic thromboembolism and major bleeding in patients with nonvalvular A-fib, according to a registry study published online January 22, 2015, ahead of print in EuroIntervention. These apparent benefits are accompanied by a “moderate” number of periprocedural complications, researchers say.
“LAA occlusion should be considered seriously for patients who cannot take anticoagulation. We think these patients really deserve to have an option,” lead author, Apostolos Tzikas, MD, PhD, of AHEPA University Hospital (Thessaloniki, Greece), told TCTMD in a telephone interview, adding that the data should be confirmed in a randomized study.
Dr. Tzikas and colleagues looked at 1,047 consecutive patients (mean age 75 years; 62% male) who underwent LAA closure with the Amplatzer cardiac plug (St. Jude Medical) at 22 centers between December 2008 and November 2013. The most common indications for closure were prior major bleeding (47%), high bleeding risk (35%), and coronary stenting leading to triple therapy (22%).
More than half of patients (57%) had permanent A-fib and the rest had a paroxysmal/persistent form of the arrhythmia; 39% had a history of stroke or transient ischemic attack (TIA).
The mean CHA2DS2-VASc score at baseline was 4.5, which predicted a 5.7% annual risk of thromboembolism. The mean HAS-BLED score was 3.1, equating to an expected 5.4% annual risk of major bleeding.
The Amplatzer device was successfully implanted in 97.3% of patients, about one-fifth of whom (20.6%) had LAA closure combined with another procedure, most commonly coronary angiography.
Periprocedural major adverse events occurred in 4.97% of patients. Events included 8 procedure-related deaths, 9 strokes, 13 cases of cardiac tamponade, and 13 major bleeds (mostly related to femoral artery access).
Closure Reduces Stroke, Bleeding
During an average follow-up of 13 months, there were significant changes in antithrombotic therapy. Aspirin monotherapy doubled from 31% to 64% between baseline and last follow-up, while warfarin or phenprocoumon monotherapy declined from 16% to 1.6%. The average duration of dual antiplatelet therapy was 3.8 months.
By 1 year, 4.3% of patients had died from any cause; no deaths were deemed to be related to the device. There also were 9 strokes and 9 TIAs during follow-up.
The annual rate of systemic thromboembolism was 2.3%, representing a 59.1% relative risk reduction compared with that predicted by the CHA2DS2-VASc score. Similarly, the 2.1% annual rate of major bleeding represented a 61.0% relative risk reduction compared with that predicted by the HAS-BLED score.
Reductions in stroke and major bleeding were even greater in the subgroup of patients who underwent LAA closure alone (without a combined intervention) and also were receiving aspirin monotherapy or no treatment at the last follow-up, as well as in the patients within that subgroup who had longer follow-up lasting at least a year. “In other words,” Dr. Tzikas and colleagues write, “the benefit of [closure] becomes more apparent with time.”
In a subset of patients who were evaluated with TEE about 7 months after the procedure, 11.6% had peridevice leak (significant in only 1.9%) and 4.4% had device thrombus. There were no strokes or TIAs during follow-up among the patients with leaks or thrombi.
Waiting for Watchman
The strongest evidence regarding LAA closure to prevent stroke in A-fib patients comes from the randomized PROTECT AF and PREVAIL trials of the Watchman device (Boston Scientific). Four-year results from PROTECT AF showed that Watchman reduced mortality and stroke compared with warfarin.
The Amplatzer plug has shown safety and feasibility for closing off the LAA in observational studies—including the current study, which is the largest conducted so far—but randomized trials have not yet been performed. That will not happen, multiple clinicians agreed, until Watchman is approved for use in the United States. Approval is expected soon, but the most recent FDA advisory panel meeting to vet the device ended with a lukewarm endorsement of its benefits relative to its risks.
“I think that this delay in deciding will also delay the adoption of [the Amplatzer cardiac plug] in the United States,” Dr. Tzikas said. “We need to have an answer in order to see what kind of study we can plan.”
Robert J. Sommer, MD, of Columbia University Medical Center (New York, NY), who has been a Watchman investigator, agreed. He told TCTMD in a telephone interview that because the Watchman studies have established that LAA closure is better than warfarin, trials of other devices, including the Amplatzer plug, will not be able to use warfarin as a comparator. Future studies will have to be head-to-head trials against Watchman, which can only go forward once the device is approved. “Everything’s on hold,” Dr. Sommer said.
In the meantime, he said, observational data like those published by Dr. Tzikas and colleagues are helpful because they will help clinicians enroll patients in future trials. “The fact that we have a set of data that shows relatively comparable safety and efficacy is going to go a long way towards helping them collect the randomized data they need,” Dr. Sommer said. “Once it’s accepted that closing the left atrial appendage is a viable alternative to chronic anticoagulation, the patients are going to be streaming in.”
Although the findings of the Amplatzer registry are positive, too much should not be read into the results, according to Zoltan G. Turi, MD, of Robert Wood Johnson University Hospital (New Brunswick, NJ).
“Given the history of [LAA occlusion] registries comparing device versus predicted stroke rates, one needs to be cautious about overinterpreting what are generally good results. There is not sufficient evidence here to reach broad conclusions about device effectiveness or device vs device efficacy and safety,” he told TCTMD in an email. “The Watchman registries made similar comparisons that showed as much as an 85% reduction versus predicted stroke rate, [but] the randomized trials have not confirmed anything like that powerful of an effect.”
Dr. Turi called the Amplatzer plug a “very promising device,” but said “the lack of a single RCT or even a registry with clinical events committees, data safety monitoring boards, core labs, etc, is really unfortunate.”
Tzikas A, Shakir S, Gafoor S, et al. Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicenter experience with the Amplatzer cardiac plug. EuroIntervention. 2015;Epub ahead of print.
- Dr. Tzikas reports serving as a consultant and proctor for and receiving research grants and an unrestricted writing honorarium from St. Jude Medical.
- Dr. Sommer reports serving on the medical advisory board for Coherex, which makes an LAA closure device, and as an investigator in the PREVAIL and Continued Access to PREVAIL (CAP2) studies of Watchman.
- Dr. Turi reports no relevant conflicts of interest.