LAA Occlusion With Amplatzer Amulet May Have Edge Over DOACs

High-risk patients with atrial fibrillation may have better outcomes with left atrial appendage (LAA) closure with the Amplatzer Amulet device (Abbott) than with direct oral anticoagulant (DOAC) treatment, an observational analysis suggests.

The rate of ischemic stroke through 2 years of follow-up was similarly low in the two groups, although LAA closure was associated with lower rates of major bleeding and both all-cause and CV mortality, lead author Jens Erik Nielsen-Kudsk, MD, DMSc (Aarhus University Hospital, Denmark), and colleagues report.

They note, however, that interpretation of the study, published in the January 11, 2021, issue of JACC: Cardiovascular Interventions, “is limited by the observational design, and the results need confirmation in randomized clinical trials.”

Mohamad Alkhouli, MD (Mayo Clinic, Rochester, MN), agrees. In an accompanying editorial, he lists several issues to consider when interpreting the results: possible selection bias; differences in the ascertainment of events between the two groups; poor medication compliance and the lack of information on dosing in the DOAC group; and an unclear explanation for the difference in all-cause mortality.

But even with those limitations, he told TCTMD, “this says that the current approach is likely safe to take selected patients, highly selected patients, who can’t tolerate DOAC and offer them left atrial appendage closure.”

Both Strategies Effective

LAA closure has been shown to be noninferior to warfarin when it comes to stroke prevention in A-fib—in the PROTECT AF and PREVAIL trials. But DOACs have become increasingly popular, and there are limited data comparing LAA closure and these newer agents. The PRAGUE-17 trial showed similar outcomes with either appendage occlusion or DOAC therapy, but the study was relatively small.

While awaiting more definitive trials, researchers have taken to making comparisons in observational data sets. The current study included data from the Amulet Observational Registry on patients who had successful LAA occlusion with the Amplatzer Amulet device at 61 centers in 17 countries between June 2015 and September 2016. All were deemed to be at high risk of stroke and bleeding based on CHA₂DS₂-VASc and HAS-BLED scores. Their outcomes were compared with those of patients with incident A-fib treated with DOACs who were identified through Danish national registries.

After propensity score-matching that used the variables in the CHA₂DS2-VASc and HAS-BLED scores, the analysis included 1,071 patients in the LAA occlusion group and 1,184 in the DOAC group. Mean patient age after matching was 75.1, and 63% of patients were men. About 30% had a history of stroke and 75% of prior bleeding.

The primary composite outcome consisted of ischemic stroke, major bleeding (BARC type 3 or greater), and all-cause mortality. Through a follow-up of 2 years, the rate was lower in the LAA occlusion group (14.5 vs 25.7 per 100 patient-years; HR 0.57; 95% CI 0.49-0.67).

There was no difference in the risk of ischemic stroke (HR 1.11; 95% CI 0.71-1.75), but LAA occlusion was associated with lower risks of major bleeding (HR 0.62; 95% CI 0.49-0.79) and all-cause mortality (HR 0.53; 95% CI 0.43-0.64). CV mortality was lower with appendage closure as well (HR 0.51; 95% CI 0.37-0.70).

The investigators note that the annual rate of ischemic stroke was low in both groups—2.1% with LAA occlusion and 1.9% with DOACs. That suggests “that both strategies of stroke prevention are effective,” they say.

As for what explains the mortality difference, Nielsen-Kudsk et al say “major bleeding, occurring at a considerably higher event rate in the DOAC cohort, could theoretically be an important contributor to the excess mortality in the DOAC group. However, it might be difficult to [prove] this hypothesis because it is often difficult to evaluate the causality between bleeding and death and major bleeding is likely underreported in the Danish Cause of Death Registry.”

Awaiting Randomized Data

The researchers acknowledge a number of potential limitations, some of which overlap with those noted by Alkhouli. They call for more trials to compare the safety and efficacy of LAA occlusion and DOACS, pointing out that several are already underway, with results expected no earlier than 2024. Those include OPTION, OCCLUSION-AF, CLOSURE-AF, CATALYST, and CHAMPION-AF.

The findings of the current analysis are very encouraging, but those trials will be needed to give a more-definitive answer, Alkhouli said. With these data, the most-solid conclusion that can be drawn is that there’s no differences in stroke, he added.

Regarding mortality, it’s likely that residual confounding plays a big role in the findings, Alkhouli said, noting that outcomes were compared between two different cohorts of patients. Those with incident A-fib, as in the DOAC group, are not typically taken for LAA occlusion before trying and failing medical therapy, whereas patients going for a procedure tend to have more long-standing A-fib, he said.

The lower rate of bleeding with LAA closure is not likely to explain the difference because the most serious bleeding—intracranial hemorrhage—occurred infrequently and at a similar rate in both groups, Alkhouli added.

For now, when making decisions about the use of LAA occlusion or medical therapy in the absence of robust randomized data, “patient selection is key,” Alkhouli stated, underscoring the importance of getting input from a multidisciplinary team. “I wouldn’t want to say that left atrial appendage closure is ready for prime time as an alternative for everybody who has atrial fibrillation who could be on a DOAC. We still need to wait. These data show that it’s likely safe to offer left atrial appendage closure to selected patients, but also caution us that with the limitations of the observational data, we do have to wait for the randomized trials before this becomes a mainstream therapy.”