Evidence Supporting Percutaneous or Surgical LAA Exclusion for Stroke Prevention Is Limited, Review Says

High-quality evidence is lacking to support either surgical or percutaneous exclusion of the left atrial appendage (LAA) to reduce the risk of stroke in patients with nonvalvular A-fib, a new systematic review concludes. And one expert agrees that there is still a need for well-conducted randomized trials to guide clinical practice, even though there are devices currently available for use.

When new devices are brought to the market, they often start getting adopted before the establishment of high-quality evidence, Richard Whitlock, MD, PhD (McMaster University, Hamilton, Canada), who was not involved in the review, told TCTMD.

“This is a field where this has happened,” he said, talking about LAA exclusion to prevent stroke. “There does have to be establishment of some clinical expertise prior to the generation of evidence, but it’s definitely time—because the expertise exists now—that we generate high-quality evidence. What this paper highlights is that there’s some encouraging evidence out there, but as of yet it’s low-to-moderate-quality evidence.”

Oral anticoagulation—though very effective at preventing stroke—is underused because of fears of bleeding and is often stopped by patients over the long term, Whitlock noted. That makes LAA exclusion via surgical or percutaneous approaches a potentially useful and more permanent alternative, he added, but further research is needed to definitively establish its effectiveness.

“Overenthusiasm, or overstating evidence, can always be dangerous in that it can impede the establishment of high-quality research and it can harm patients,” Whitlock said. “Until we know that this works, it should be somewhat stabled in research environments.”

The review was published online July 12, 2016, ahead of print in Circulation: Cardiovascular Quality and Outcomes.

Watchman Dominates Evidence

For decades, oral anticoagulation has been the mainstay of stroke prevention in patients with A-fib, with newer direct-acting agents cutting into warfarin’s dominance in recent years. But LAA exclusion—either with surgery or with percutaneous devices—has emerged as a possible alternative to long-term anticoagulation. Percutaneous options include the Amplatzer occluder (St. Jude Medical), the Watchman (Boston Scientific), and the Lariat suture device (SentreHeart).

To assess the state of the evidence regarding LAA exclusion, lead author North Noelck, MD, MPH (VA Portland Health Care System, Portland, OR), and colleagues performed a systematic review that included two RCTs and 11 observational studies evaluating percutaneous devices and three RCTs and four cohort studies evaluating surgical approaches.

In the percutaneous realm, the Watchman, which was approved by the US Food and Drug Administration in March 2015, has undergone the most rigorous evaluation. Results of the two trials testing the device—PROTECT-AF and PREVAIL—provide “low-strength” evidence that LAA occlusion carries risks of stroke and mortality similar to those seen with warfarin, the researchers report, noting, however, that those studies were limited to patients who were eligible for long-term oral anticoagulation.

The investigators also point out that there is evidence of significant procedure-related harms with percutaneous LAA closure. In PROTECT-AF, 10.6% of patients had a safety event, with more than half of those occurring on the day of the procedure. That rate dropped, however, to 2.2% in the more recent PREVAIL trial.

Across both randomized and observational studies, serious periprocedural adverse events—most commonly pericardial effusion with or without associated tamponade, bleeding, device thrombus, and device embolization—were reported in 1.6% to 13.6% of patients.

The data are not robust enough to compare safety events across devices, according to the authors, who note that serious periprocedural events have been reported for all of them. Assessments of longer-term safety are hampered by attrition, variation in the duration of follow-up, and a lack of standardization in adverse event reporting, they add.

“The procedure-related harms of percutaneous left atrial appendage exclusion need to be looked at and understood by both the doctors that are performing this and the patients that are undergoing the procedure,” Noelck told TCTMD.

Data are even sparser for surgical exclusion of the LAA, with “low-strength” evidence suggesting that it does not introduce harm when performed during cardiac surgery for another indication, the authors report. Evidence is insufficient, however, to assess its effectiveness for reducing stroke.

“Therefore, until more data become available, surgical LAA exclusion should likely not influence decision-making about future [oral anticoagulant] therapy,” Noelck et al write.

Ineligible for Long-Term Anticoagulation

There are multiple clinical scenarios in which percutaneous LAA exclusion may be a potentially useful option, the authors say, pointing to patients who might develop more substantial bleeding risk from oral anticoagulation over the long term, those who prefer placement of a device instead of long-term drug treatment, and those who are not candidates for long-term anticoagulation.

Although the Watchman trials did not include the latter group of patients, several observational studies have studied that population, with most finding low stroke rates over 1 to 2 years of follow-up. In most of those studies, patients received dual antiplatelet therapy, which has been shown to have a risk of major bleeding similar to that seen with warfarin in A-fib patients.

“Thus, as long as the protocol for the use of LAA closure devices includes dual antiplatelet therapy for any significant length of time, it may not be an attractive option for patients who are at high risk for bleeding complications and who do not wish to take, or have contraindications to, warfarin,” the authors point out.

Currently, patients who are ineligible for long-term oral anticoagulation are the most likely to be treated with LAA exclusion in everyday practice, despite the dearth of studies in this population, Whitlock said.

“It’s a challenging scenario for clinical practice, but in terms of the academics or researchers out there, this is an area ripe for further research,” noted Whitlock, who is the principal investigator for the LAAOS III trial evaluating surgical removal of the LAA in patients with A-fib who are undergoing cardiac surgery for another indication.

But there is no doubt more trials are needed, he said: “Until then, we’re stuck in this dilemma [where] many physicians are applying these procedures to patients who are not included in these studies and that we don’t have evidence for.”

Noelck et al note that there several ongoing studies in addition to LAAOS III, including evaluations of the recently developed LAmbre and Occlutech percutaneous devices and the PRAGUE-17 trial comparing Watchman and apixaban (Eliquis; Bristol-Myers Squibb).

While awaiting information from those studies, Noelck said that percutaneous LAA exclusion “should be in the physicians’ armamentarium,” recognizing that many patients will not accept long-term anticoagulation or will become nonadherent within a few years.

“It’s my opinion that further study needs to be done to evaluate the effectiveness of the left atrial appendage exclusion devices, in particular whether or not we’re preventing strokes or doing harm on these populations that I think most doctors are very interested in using them in,” Noelck said, referring to those who are not candidates for anticoagulation.

“It’s probably a population that [is most likely to benefit] but I don’t think we can say that with any certainty given the lack of a randomized controlled trial,” he said.