LAAO May Be an Option for Anticoagulated AF Patients With Breakthrough Stroke

Patients with atrial fibrillation (AF) and a history of breakthrough stroke—an ischemic stroke that occurs despite use of oral anticoagulation—have a heightened risk for subsequent cerebrovascular events. Use of left atrial appendage occlusion (LAAO) may provide an alternative treatment approach, findings from the OCEAN-LAAC registry suggest.

“Patients who experience ischemic stroke with an oral anticoagulant are at high risk, and continued treatment with an oral anticoagulant can be inadequate,” researchers led by Tadatomo Fukushima, MD (Kokura Memorial Hospital, Kitakyushu, Japan), write in a paper published online recently in JACC: Clinical Electrophysiology. “As a new treatment option, LAA closure for patients at high risk of embolism is warranted.”

OCEAN-LAAC included a cohort of patients undergoing LAAO, with the risk of ischemic stroke over about a year of follow-up being higher in patients with prior breakthrough strokes than in those with no history of ischemic stroke or a prior stroke while not taking oral anticoagulation.

However, stroke rates were lower than seen in a prior study that included patients who continued anticoagulation instead of undergoing LAAO.

Still, Fukushima et al acknowledge the need for further studies that compare LAAO with continued anticoagulation and that evaluate optimal oral anticoagulation after the procedure in patients with breakthrough strokes.

Neurologist David Seiffge, MD (Inselspital, Bern University Hospital, Switzerland), estimates that 30% to 40% of all AF-related strokes occur in patients who are already on an oral anticoagulant.

“Current treatment options like switching the anticoagulant to another one, what we have done historically, doesn’t reduce the risk of stroke,” Seiffge told TCTMD. “We are desperately looking for new treatment options, and left atrial appendage closure is of course one which is very interesting.”

The OCEAN-LAAC Registry

The new retrospective analysis focused on 1,418 patients (mean age 78 years; 67.2% men) enrolled in OCEAN-LAAC, a prospective registry of patients with nonvalvular AF undergoing LAAO in Japan. The median CHA₂DS₂-VASc and HAS-BLED scores were 5.0 and 3.0, respectively.

Roughly one-quarter (24.4%) had a history of breakthrough stroke, 11.1% had a prior ischemic stroke while not taking oral anticoagulation, and 64.5% had no history of ischemic stroke.

LAAO was performed with the Watchman FLX device in two-thirds and the earlier-generation Watchman 2.5 device (both Boston Scientific) in the others. Procedural success was 94% overall, with no differences across the three groups defined by stroke/anticoagulation history. There were no in-hospital deaths or strokes. Uptake of oral anticoagulation at discharge was high overall (95.5%), with significantly lower discontinuation rates during the first year of follow-up in patients with a history of breakthrough strokes prior to LAAO.

Current treatment options like switching the anticoagulant to another one, what we have done historically, doesn’t reduce the risk of stroke. David Seiffge

Transesophageal echocardiography performed at 45 days and 1 year showed no differences between groups in peridevice leak or device-related thrombosis.

The co-primary endpoints of the analysis were CV death and ischemic stroke, evaluated over a median follow-up of 367 days. The rate of CV death was 2.2% in patients without prior stroke, 3.5% in patients with a history of breakthrough strokes on anticoagulation, and 3.8% among patients with a prior ischemic stroke while not on anticoagulation, a nonsignificant difference across groups (P = 0.51).

Incidence of ischemic stroke after LAAO, however, was significantly higher among patients with a prior stroke while taking oral anticoagulation than among patients without a prior stroke history (4.0% vs 1.6%; subdistribution HR 2.62; 95% CI 1.17-5.86). Risk was not significantly increased in patients with a prior ischemic stroke while not taking oral anticoagulation (2.5%; subdistribution HR 1.24; 95% CI 0.36-4.28).

In the subgroup of patients with a history of breakthrough strokes before LAAO, rates of CV death and ischemic stroke were no different when comparing patients who did versus did not discontinue oral anticoagulation during follow-up. Fukushima et al caution, however, that “discontinuation of oral anticoagulation after LAA closure in a high-risk cohort needs to be determined carefully based on each [individual’s] bleeding risk.”

In terms of other outcomes, rates of all-cause mortality and any stroke were similar across the three groups. Any bleeding and GI bleeding occurred least frequently in patients with a prior history of breakthrough strokes.

Trial Data on the Way

Seiffge said it’s difficult to use a study like this to determine whether LAAO is superior to continuing oral anticoagulation, since all patients underwent the procedure.

“But the study gives you an idea that it seems to be quite safe and feasible to do the intervention. I think that’s the first step,” he said. “And the rate of strokes in this population who actually received left atrial appendage closure as part of the study is very low, much lower than what we know from [a] literature comparison. So it’s an indirect comparison, but that’s still helpful.”

He noted that in his group’s study, STR-OAC LAAO, there was a comparator group of patients who did not undergo appendage closure and who had a much higher rate of stroke recurrence compared with those who received the procedure.

“For clinical purposes, this is still a retrospective observational study—so it’s a noninterventional, nonrandomized study,” Seiffge said. “At best, it is hypothesis-generating, so it’s not yet going to change guidelines of course, but I’m quite sure that the next guidance will at least mention left atrial appendage closure as an option for those patients.”

He pointed out there is an ongoing trial called ELAPSE, for which he is on the steering committee, that is randomizing patients with breakthrough strokes to LAAO plus oral anticoagulation or anticoagulation alone. It won’t be completed for several more years, but “in the meantime, I think these results [from OCEAN-LAAC] are encouraging to explore left atrial appendage closure as an option for patients who fail anticoagulation therapy on an individual patient basis and not as a general recommendation,” Seiffge said.