Watchman LAA Occluder Bounces Back as Alternative to OAC in CHAMPION-AF

NEW ORLEANS — It may be reasonable for people with atrial fibrillation (Afib) to undergo percutaneous left atrial appendage (LAA) closure even if long-term anticoagulation is an alternative, according to the large CHAMPION-AF trial presented here.

Three years after LAA closure with the Watchman FLX device, statistical criteria were met for the device’s non-inferiority to non-vitamin K antagonist oral anticoagulant (NOAC) therapy alone on the basis of a composite of death from cardiovascular causes, stroke, or systemic embolism (5.7% vs 4.8%, HR 1.20, 95% CI 0.87-1.66, P<0.001 for non-inferiority).

What’s more, the non-inferior efficacy of LAA occlusion was accompanied by a reduction in non-procedure-related bleeding (10.9% vs 19.0%, HR 0.55, 95% CI 0.45-0.67, P<0.001 for superiority), reported Saibal Kar, MD, of Los Robles Medical Center in Thousand Oaks, California, at the American College of Cardiology (ACC) annual meeting. CHAMPION-AF data were simultaneously published in the New England Journal of Medicine.

“Watchman FLX left atrial appendage closure should be considered as an alternative to NOACs in a shared decision-making process with Afib patients who are deemed suitable for long-term oral anticoagulation,” Kar concluded.

At first glance, CHAMPION-AF gives some redemption to LAA occluders after CLOSURE-AF, a smaller randomized trial that failed to show that LAA closure (using various devices) was non-inferior to NOAC therapy in a somewhat older, higher-risk cohort.

It could be argued, however, that the present trial relied on questionable statistical criteria for handing non-inferiority to the intervention: the case for the Watchman FLX was helped by the lower-than-expected observed event rate (expected 12% in each group) and a generous non-inferiority margin of 4.8 percentage points in CHAMPION-AF.

“Proving a negative is hard. The greatest threat to a false negative is insufficient power, and the fact that the actual incidence of a primary endpoint event in each group was less than half that anticipated is difficult to ignore. This finding is an increasingly common observation, in which the modern-day risk of adverse consequences of atrial fibrillation is (fortunately for our patients) substantially lower than in previous years,” wrote Gregory Marcus, MD, of the University of California San Francisco, in an accompanying editorial.

“Although the data in the current trial support expanding consideration of left atrial appendage closure for selected patients on a case-by-case basis, they are likely to be insufficient for a definitive declaration that this approach is as efficacious as conventional NOAC therapy in the great majority of patients with atrial fibrillation,” Marcus cautioned.

Additionally, although LAA occlusion is intended for thromboembolic protection — given that most thromboembolic complications attributed to Afib originate in the LAA — there was a trend toward more strokes in the LAA closure group in CHAMPION-AF (3.6% vs 2.5%, HR 1.46, 95% CI 0.94-2.27).

“The between-group difference in the incidence of ischemic stroke or systemic embolism that was observed in the CHAMPION-AF trial was 1 percentage point over the course of 3 years, which corresponds to a 0.3% increase per year among patients who received the device,” Kar and colleagues reported. “The planned 5-year assessment of the CHAMPION-AF trial will help ascertain whether the difference in the rate of ischemic stroke or systemic embolism observed in this trial persists.”

“In any case, the story is evolving,” said ACC session discussant Jose Joglar, MD, of UT Southwestern Medical Center in Dallas. Patients are coming in lower-risk, he said, and there’s a reduced need for anticoagulation after successful ablation. At the same time, the Watchman procedure is also getting safer, and there is work on limiting the need for postprocedure anticoagulation and antiplatelets there.

Percutaneous LAA closure currently holds a class IIa recommendation in U.S. guidelines for Afib patients at high risk for stroke who have contraindications to long-term anticoagulation. On the basis of patient preference alone, LAA occlusion may be a reasonable alternative to anticoagulation, a weaker IIb endorsement.

“We’re already supposed to be doing shared decision-making with our patients about these devices,” commented Pamela Mason, MD, of UVA Health in Charlottesville, Virginia, at an ACC press conference. “It’s important to note that there are other trials we’re waiting for,” she added, citing the CATALYST investigation on another commercially available LAA occluder, the Amulet.

Study Details

For the CHAMPION-AF trial, Kar’s group sought Afib patients who were at increased risk for stroke (CHA₂DS₂-VASc score ≥2 for men and ≥3 for women) and randomized 3,000 to LAA occlusion or NOAC therapy alone.

The cohort had a mean age of 71.7 and was 31.9% women. CHA₂DS₂-VASc scores averaged 3.5 points and HAS-BLED scores 1.3 points. Just under half of participants had had a prior Afib ablation procedure.

The LAA occlusion group got a successful Watchman FLX implant in 98.8% of cases. Following device implantation, patients took a NOAC plus aspirin, NOAC monotherapy, or dual antiplatelet therapy for 3 months, after which aspirin or P2Y12 inhibitor monotherapy was recommended.

The incidence of device-related thrombus, which was defined as any tissue density on the face of the implant at 4 months per CT or transesophageal echocardiography, reached 4.8%. Ultimately, 1.8% 0f the Watchman FLX group had a clinically relevant device-related thrombus that resulted in resumption of oral anticoagulation, and two of these individuals with a device-related thrombus had a stroke.

Meanwhile, effective closure, defined as a residual leak no greater than 3 mm, was observed in 98.6% of patients at 4 months.

Kar cautioned that the study results may not apply to all LAA closure devices. Generalizability may also be limited to Afib patients as a whole, as the trial had excluded people with advanced heart failure and low ejection fraction.

Additionally, the details of which NOACs were used in CHAMPION-AF were not disclosed. Marcus pointed to apixaban (Eliquis) as a NOAC with a particularly good track record of low bleeding risk.