DOACs Safe, Effective in A-fib Patients With Preexisting LAA Thrombus

Direct oral anticoagulants (DOACs) can safely and effectively resolve left atrial appendage (LAA) thrombi in patients with atrial fibrillation, a single-center study reassures.

Numerous trials—from RE-LY to ROCKET AF and ARISTOTLE—have demonstrated the benefit of DOACs over warfarin as preventive measures against stroke in patients with A-fib, and the agents are becoming increasingly popular. But less is known about the best anticoagulation strategy in situations where imaging has already identified an existing LAA thrombus, Adam Fleddermann, MD (Saint Luke’s Mid America Heart Institute, Kansas City, MO), and colleagues say.

Michael L. Main, MD (Saint Luke’s Mid America Heart Institute), senior author of the study, which was published online recently in the American Journal of Cardiology, observed that while DOACs are approved for thromboembolic prophylaxis in patients with atrial fibrillation, “there isn’t any express approval for treatment of existing LAA thrombus.”

“The standard of care currently is really dependent on institution and physician,” he told TCTMD. “There are certainly some people who would strictly use warfarin if they found a left atrial appendage thrombus, whereas many physicians are already using these newer direct-acting drugs for that indication. . . . It’s just an area that has not been well studied.”

So far, published reports have included a small registry of rivaroxaban-treated patients and a few case series, the researchers observe in their paper.

Commenting on the results for TCTMD, Brian Whisenant, MD (Intermountain Medical Center Heart Institute, Salt Lake City, UT), said, “The paper is concise and clear, and it answers a specific question about whether DOACs are appropriate therapy when thrombus is visualized in the left atrial appendage. And it shows that they work. . . . That hasn’t been demonstrated very well in the past and it’s useful to know that.”

Adding ‘Ample Evidence’

To expand the evidence base, Fleddermann et al looked at 33 patients in whom LAA thrombus had been identified on transesophageal echocardiography (TEE) before being treated with a DOAC: 18 received apixaban (Eliquis; Bristol-Myers Squibb), 10 dabigatran (Pradaxa; Boehringer Ingelheim), and five rivaroxaban (Xarelto; Bayer/Janssen).

Of the 16 patients who underwent follow-up TEE, 15 saw their LAA thrombus resolve. The mean time to resolution was 112 days. The one patient whose condition did not resolve had a residual thrombus area of 0.8 cm2 (increased from an initial 0.5 cm2) that remained after 122 days of treatment with rivaroxaban.

None of the 16 patients with TEE follow-up experienced cardioembolic or bleeding events. Of the 17 who did not undergo follow-up imaging, who tended to be older and have more comorbidities, one died of a retroperitoneal bleed 28 days after starting a DOAC and another had an ischemic stroke 484 days after DOAC therapy was initiated.

“Although these results are descriptive and limited in number of patients, we believe this is ample evidence that DOACs are relatively safe and efficacious in treatment of patients with AF and concomitant LAA thrombus,” Fleddermann et al conclude.

Practice has been mixed thus far, with some clinicians still drawn to warfarin, Main said, because “people still have some questions about the direct-acting oral anticoagulants. For instance, in patients with mechanical heart valves, there was early interest in using these drugs for that indication, and of course dabigatran failed miserably [in that regard] and it’s contraindicated [for this group]. So I think some people still have lingering doubts about how these drugs, particularly at the doses used, will work with preexisting thrombus versus just chronic thromboembolic prophylaxis.”

Whisenant said warfarin still likely predominates in practice, and that while some have also used DOACs for this indication, it was unclear how their ability to dissolve thrombi matched up to warfarin’s efficacy. “Now we have something to point to to say that they work, so it’s great,” he observed.

Even if the thrombus resolves, the vast majority of these patients ought to remain on lifelong anticoagulant therapy, Main noted. And in cases when the thrombus doesn’t go away, he added, “typically what we would do in these patients is keep them on anticoagulation on the hopes that over time it would resolve.”

Most clinicians are already familiar with how to use DOACs, Main said, noting, “The point of our paper is if you have a patient with a left atrial appendage thrombus who is otherwise a good candidate for a direct-acting drug—in other words, they have good renal function, which is one of the main reasons these drugs wouldn’t be used—we now have limited but pretty strong evidence that these drugs are efficacious in this setting.”

Asked by TCTMD whether the results bolster the case for DOACs as an alternative to LAA closure for stroke prevention as well, Main said they do not. “The multicenter WATCHMAN left atrial appendage closure trials were designed as device versus warfarin therapy,” he observed. “So we don’t know the relative efficacy of direct-acting oral anticoagulants versus LAA closure—I don’t think our data sheds any light on that issue.”

Whisenant agreed that the implications for LAA closure are slim, noting: “We reserve left atrial appendage closure for patients who are not good candidates for DOACs. And I think that remains the case here; I don’t think this changes very much.”

It’s known, though, that DOACs have a lower risk of intracerebral bleeding compared with warfarin, he said. For patients at higher bleeding risk who present with LAA thrombus, “we would very much prefer to treat with DOACs rather than warfarin, and this tells us we can do that safely,” Whisenant said. “For some of those high-risk patients, once the thrombus is resolved, then we could go ahead and move to left atrial appendage closure.”