TAVR With LAAO Non-inferior to TAVR Plus Medical Therapy

SAN FRANCISCO — Left atrial appendage occlusion (LAAO) at the time of transcatheter aortic valve replacement (TAVR) using the WATCHMAN 2.5 device (Boston Scientific) is feasible and non-inferior to TAVR followed by medical therapy on the composite endpoint of all-cause mortality, stroke, and major bleeding in patients with both atrial fibrillation (AF) and severe aortic stenosis.

However, arterial and venous thromboembolism occurred more often in patients who had the combined procedure compared with TAVR and medical therapy.

Based on past trials, AF typically is present in about 33%–40% of patients undergoing TAVR.

"The duration of WATCHMAN was only 45 minutes added to the procedure," Samir Kapadia, MD, of the Cleveland Clinic, told attendees here at Transcatheter Cardiovascular Therapeutics 2023. The results of the WATCH-TAVR study were simultaneously published online in the journal Circulation.

Compared with TAVR plus medical therapy, hospital length of stay and rate of acute kidney injury were no different. Using WATCHMAN with TAVR, pericardial effusion occurred in four patients and required only draining. Kapadia said the combination procedure required 40 mL more contrast volume.

This non-inferiority study was investigator initiated, prospective, and involved 34 centers in North America. It enrolled 349 patients (TAVR + LAAO, n = 177; TAVR + medical therapy, n = 172) undergoing transfemoral TAVR and evaluated them for the primary endpoint of the first occurrence of all-cause mortality, any stroke, or life-threatening or major bleeding events within 24 months.

TAVR + LAAO patients received warfarin plus antiplatelet therapy for 6 weeks after the procedure followed by up to 6 months of dual antiplatelet therapy at the discretion of the treating physician. Medical therapy was at the physician's discretion in the TAVR + medical therapy group.

All patients were included in the analysis, although in the TAVR + LAAO group, 15 did not undergo LAAO for various reasons, and 8 were lost to follow-up or withdrew consent. For the TAVR + medical therapy arm, 21 did not have TAVR, were lost to follow-up, or withdrew consent.

At baseline, the groups were well matched, with an age of approximately 81 years, 39% female, about 4 out of 5 with congestive heart failure, 92% with hypertension, and just about 13% with a previous transient ischemic attack or ischemic stroke.

Nearly half of each group had paroxysmal AF, persistent AF (TAVR + LAAO, 17.5%; TAVR + medical therapy, 23.3%), or permanent AF (23.2% and 19.2%, respectively). About 70% of each group were on anticoagulation therapy, but they differed on the kind of therapy: more on warfarin in the former group, and more on direct oral anticoagulants in the latter arm.

General anesthesia was used in 84% of the combined procedure vs 36% of the TAVR-alone group, Kapadia noted. Additionally, the WATCHMAN procedure added 43.6 ± 26.8 minutes. Hospital stay was 3.5 days for the combined procedure vs 4 days for TAVR alone. About 90% of patients in each group were discharged home. There was one in-hospital death in each group.

Primary Outcome Favors TAVR + LAAO

The groups were similar for the primary outcome of death, stroke, or major bleeding out to about 4 months, after which time the TAVR + LAAO group showed a reduced primary outcome compared with the TAVR + medical therapy arm. For the medical therapy group, Kapadia reported a 37.2% event rate at two years compared to 33.9% in the combined group (hazard ratio [HR], 0.86; 95% CI, 0.60 - 1.22; P _{noninferiority} < .001.

As a non-inferiority trial, WATCH-TAVR was not powered to look at individual components of the composite endpoint. Thus, analysis of the individual components did not reach statistical significance. However, trends favored TAVR + LAAO in terms of all-cause mortality (20.9% vs 22.7%) and for all strokes (5.7% vs 7.0%), but major bleeding occurred more often in the TAVR + LAAO arm (19.8% vs 17.4%).

The risk of major or life-threatening bleeding was 35% greater in the first 6 months post-TAVR + LAAO, after which time the risk was actually 37% lower compared with the TAVR + medical therapy arm.

A secondary endpoint of arterial or venous thrombosis or embolism occurred in 9% of the TAVR + LAAO arm vs 1.7% of the medical therapy arm (HR, 5.03; 95% CI 1.47 - 17.26), mainly accounted for by venous thrombosis.

Kapadia noted that this study was done with the WATCHMAN 2.5, and now that the WATCHMAN FLX is available, pharmacotherapy will be different, "and the lesser need for anticoagulation may help with the bleeding complication early." So, a limitation of the trial is that it does not involve the more modern devices and practice, and its duration was limited to 2 years, he said.

Designated discussant Megan Coylewright, MD, MPH, of Erlanger Heart and Lung Institute in Chattanooga, Tennessee, began by congratulating Kapadia "not just for this study, but for your leadership back in 2016 when you first thought up this study. This was an investigator-initiated study."

She cautioned that a non-inferiority trial "does not mean that we show that these things are the same. It means that the comparator is not terrible. It's not, you know, unacceptably worse." Then she pointed out that one third of the TAVR + medical therapy patients were not taking any anticoagulant therapy at 2 years.

"How do you think that poor adherence in the context of a non-inferiority study design influenced your results?" she asked Kapadia.

"Of course, they have to live 2 years to say that they are not taking anticoagulation," he replied. "So, if you take a retrospective analysis of saying the patients who are not on anticoagulation, how they are doing, of course, they are self-selected, but it is very unlikely that they are going to do as well without anticoagulation."

Coylewright then asked, "Where does this bring us for next steps?" noting that some of her colleagues say, "Why don't you just do TAVR [and] WATCHMAN together now? Why not?"

"Well, because we're not reimbursed to do them in the same setting as our surgical partners are," Kapadia said simply. In his discussions with Medicare, he learned that it usually takes about 3 years to get Medicare reimbursement approved. Because of a lack of reimbursement, he turned to the manufacturer of WATCHMAN for study funding.

Finally, Coylewright asked if it is necessary to have a randomized trial for every combination of procedures to gain the evidence necessary to have reimbursement to provide these choices to patients for whom it would be an appropriate option. "Or can we utilize our mandated national registries to provide continued evidence [for] developments?" she wondered.

Kapadia disclosed the following relationships: grant/research support from Boston Scientific, stock/shareholder equity in Navigate, and advisory board member of Admedus. Boston Scientific provided trial funding. Coylewright reported a consultant fee/honoraria/speaker's bureau relationship with Edwards Lifesciences, Boston Scientific Corporation, Medtronic, Occlutech, and Abbott.

Transcatheter Cardiovascular Therapeutics 2023. Presented October 24, 2023.

Circulation. Published online October 24, 2023. Abstract

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