WATCHMAN™ FLX and the OPTION Clinical Trial: An Alternative to Lifetime Oral Anticoagulant Use in Post-ablation Patients
Interview With Brad Sutton, MD, Chief Medical Officer, Atrial Fibrillation Solutions, Boston Scientific
Interview With Brad Sutton, MD, Chief Medical Officer, Atrial Fibrillation Solutions, Boston Scientific
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EP LAB DIGEST. 2025;25(1):ONLINE ONLY.
To set the stage for a discussion on the OPTION clinical trial, which compared left atrial appendage closure (LAAC) and oral anticoagulants as stroke risk reduction strategies for post-ablation patients, can you give us an overview of how commonly cardiac ablation procedures are used to treat atrial fibrillation (AF), and how they work? What are some of the latest ablation technologies available to treat patients today?
Catheter ablation of atrial fibrillation (AF) is truly one of the cornerstones of what electrophysiologists do every day. This procedure has been around for over 40 years and has evolved from what historically has been radiofrequency (RF) or cryoablation based, both of which are thermal ablation technologies that have some inherent risks. In recent years, the number of patients with AF who have undergone an in-hospital cardiac ablation procedure to prevent symptoms has grown significantly, with approximately 350,000 AF ablations performed in the United States per year.1
The latest technology and a very important evolution in the field is pulsed field ablation (PFA), such as the FARAPULSE™ Pulsed Field Ablation (PFA) System (Boston Scientific), which received United States Food and Drug Administration (FDA) approval in January 2024.
The most important thing to know about PFA is that it uses high-output electrical fields to irreversibly electroporate tissue. With the appropriate waveform, catheter design, and dosing strategy, it may ablate atrial tissue in a relatively tissue-selective way. This helps mitigate the risk of collateral damage to the esophagus, pulmonary veins, and phrenic nerve, concerns which have plagued thermal energies. It really is an amazing time in EP where we now have a safer type of ablation procedure with PFA. In our ADVENT randomized trial, we showed that PFA is at least as efficacious as RF or cryoablation and affords excellent procedural predictability.2 We know that the learning curve is short and that PFA with the FARAPULSE system is a predictable, reproducible procedure.
However, it is important to note that, in the OPTION trial, only thermal (radiofrequency, cryotherapy, or laser) ablation energies were used, as PFA was not commercially available during the enrollment period for the OPTION trial.
What kind of challenges do some patients who undergo a cardiac ablation for their AF face in terms of long-term stroke and bleeding risks?
There are several reasons to address AF in patients, both in terms of the symptoms they experience and in addressing their risk for stroke. Patients with AF often feel poorly, such as shortness of breath or fatigue, because their heart rate is rapid or irregular. So, there is a symptom benefit with AF ablation.
But more importantly, AF also predisposes patients to stroke through ineffective contraction of the atrium. The left atrial appendage of the heart, in particular, is prone to sluggish blood flow and development of blood clots in the setting of AF, which if embolized, can cause stroke or systemic embolism. Approximately 70% of patients who have had an AF ablation are at high risk of stroke based on their CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or TIA or thromboembolism, vascular disease, age, sex category) score.3 The historic treatment approach for stroke risk reduction has been systemic oral anticoagulation (OAC) with the attendant risks of bleeding, with LAAC with the WATCHMAN device indicated for patients with an appropriate rationale to avoid long-term OAC.
As an electrophysiologist, when patients would talk to me about ablation, they wanted to know about the risks of the procedure, what to expect in terms of the outcome and symptom relief afterward, and when they could stop taking their OAC. The answer is that if their CHA2DS2-VASc or overall stroke risk was elevated, as is the case for many patients, they could not get off their blood thinners per the AF treatment guidelines. AF ablation is not always successful in maintaining sinus rhythm long term, and stopping OAC can put patients with ongoing asymptomatic AF at risk of cardioembolic stroke. Alternatively, continuation of long-term OAC comes at the cost of increased risk of bleeding. So, this real-world issue, as patients and providers sought alternatives to lifelong anticoagulation after ablation, became the basis of our rationale for the OPTION clinical trial.
Tell us more about why Boston Scientific set out to execute the OPTION clinical trial with the WATCHMAN FLX™ LAAC Device?
We hypothesized that the WATCHMAN FLX device—which is the predecessor to the WATCHMAN FLX™ Pro LAAC Device with a well-established body of clinical evidence supporting its efficacy and safety profile—had the potential to provide patients undergoing AF ablation with a one-time option for reducing their stroke risk without the need for continuous OAC and its associated bleeding risk.
Planning for the OPTION trial goes back 9 years, so this represents a significant global investment of time and resources to plan, execute, and report on this clinical trial. With the goal of providing a stroke risk reduction alternative to blood thinners for patients in the setting of AF ablation, the OPTION trial was the first prospective randomized, head-to-head study comparing the WATCHMAN FLX device to the current standard of care—OAC (95% direct oral anticoagulants [DOACs])—after an ablation procedure. The study design included 1600 patients randomized 1:1 after AF ablation; all patients received either a WATCHMAN FLX implantation or were prescribed guideline-directed long-term OAC and then followed for 3 years. This trial has the potential to both expand the indication for the WATCHMAN FLX device and make LAAC an alternative first-line therapy for post-ablation patients.
What is new or different about the OPTION trial compared to your past trials for the WATCHMAN technology?
Historically, WATCHMAN studies were done in an era when warfarin was the dominant anticoagulation regimen, so the OPTION trial provided some evidence for a more modern anticoagulation strategy, in post-ablation patients, specifically. It was also fundamentally different from more recent trials such as PINNACLE FLX, which looked at shorter-term safety and efficacy outcomes with the WATCHMAN FLX without a comparator arm.
What were the key primary endpoint outcomes of the OPTION trial, as presented at the American Heart Association’s (AHA) Scientific Sessions 2024 and published in the New England Journal of Medicine (NEJM)?4
The primary composite endpoints demonstrated that the WATCHMAN FLX device was equally effective to OAC (95% DOAC), with a superior safety profile, which allowed patients to eliminate continuous medication use and significantly reduce bleeding risk while maintaining stroke protection. The primary efficacy endpoint was a composite of all-cause death, stroke, or systemic embolism at 36 months, with the data showing statistical noninferiority of the device to OAC (5.3% vs 5.8%; P<0.0001). The primary safety endpoint was nonprocedural major bleeding or clinically relevant non-major bleeding at 36 months, with the WATCHMAN FLX device demonstrating statistical superiority to OAC (8.5% vs 18.1%; P<0.0001). The data also met the combined secondary endpoint of procedural and nonprocedural major bleeding at 36 months, with the data demonstrating statistical noninferiority of the WATCHMAN FLX device to OAC (3.9% vs 5.0%; P<0.0001).
In summary, the trial demonstrated that—in the setting of patients who undergo AF ablation—the WATCHMAN FLX device provides similar stroke prevention over 36 months, which allowed patients in the trial to come off their blood thinner, significantly reducing their post-procedural risk of bleeding relative to being on a blood thinner over that same 3-year period.
What are the potential implications of these positive findings for physicians and patients? Is Boston Scientific seeking a labeling change based on the new data?
Both primary endpoints were met with a high degree of statistical significance, so we were thrilled to present those results at the AHA Scientific Sessions 2024 and in the NEJM. We intend to submit to the FDA a potential labeling update and we not only believe that these are practice-changing findings, but potentially guideline-changing. The AF guidelines were updated this past year, but the guidelines committees will occasionally submit interim consensus updates or recommendations before the next formal round of updates. Given this data, it is possible that patients who have undergone or are undergoing an AF ablation will be recommended to consider appendage closure and cessation of their anticoagulation given the equivalency demonstrated in the OPTION trial.
Some of the patients in the trial received their WATCHMAN FLX device concomitantly to the ablation, others sequentially. In light of the recent Centers for Medicare and Medicaid Services’ (CMS) ruling on reimbursement for concomitant LAAC and ablation procedures, will we be seeing more insights about the subset of concomitant patients?
Yes, it is remarkable that so many patients had concomitant procedures. In the trial, approximately 60% of patients had their WATCHMAN FLX device implanted 90-180 days following their ablation procedure, and approximately 40% had the 2 procedures performed concomitantly.
Keep in mind there was no prespecified randomization of concomitant versus sequential, although we will still be able to learn from the clinical outcomes of those who underwent concomitant procedures. There is also the new concomitant Diagnosis Related Group (DRG) that went live in October 2024, whereby CMS is reimbursing hospitals for concomitant WATCHMAN and cardiac ablation procedures. So, early in 2025, we do intend to dive deeper and present what those relative outcomes look like. We are excited to better understand where concomitant makes sense and how that may be incorporated into physicians' workflows.
Are the OPTION trial results an early indication of CHAMPION-AF trial results?
The results from the OPTION clinical trial support the consideration of WATCHMAN implantation as an alternative to OAC in moderate-to-high risk patients with nonvalvular AF (NVAF) in a post-ablation setting. While the OPTION trial only looked at this specific subset of patients (post-cardiac ablation), it may provide some insight into clinical outcomes of LAAC in a patient population that is lower risk than is typically implanted today—more akin to what we expect patients to look like in the CHAMPION-AF trial. Recall that the CHAMPION-AF trial will evaluate the efficacy and safety of the WATCHMAN FLX device within a broader OAC-eligible, non-valvular AF patient population in a head-to-head fashion compared to DOACs, the best-in-class drugs for stroke risk reduction in these patients. Patients in the CHAMPION-AF trial have AF with an elevated CHA2DS2-VASc risk score, in this case, CHA2DS2-VASc of 2 in men or 3 in women. Randomized patients had to be able to tolerate long-term OAC and will be followed for 3 years as well.
The bottom line is that both studies could provide patient access across a broader spectrum of risk levels, including patients at low to moderate risk for bleeding.
What is coming up next in terms of additional clinical evidence for the WATCHMAN FLX and current-generation WATCHMAN FLX Pro devices?
CHAMPION-AF is top of mind for us as we conclude the study and prepare for the presentation of the data in the first half of 2026.
In addition to the CHAMPION-AF outcomes, we also plan to share future subgroup analyses from the OPTION trial, including data on concomitant patients. We are looking to explore what patients might benefit most from concomitant therapy and how to optimize that workflow and clinical outcomes. There are a couple of ways to address this, both in terms of real-world evidence and prospective registries. We may also discover that the combination of effective rhythm control via AF ablation with LAAC and prevention of cardioembolic events may favorably impact brain perfusion and cognitive function over time.
Meanwhile, the ongoing LAAOS-4 collaborative research trial led by the Population Health Research Institute will complement the CHAMPION-AF and OPTION trials and explore whether the patients with NVAF at highest risk for stroke experience superior risk reduction with a combined LAAC and OAC therapy. If positive, we believe the outcomes of the trial will lead to expansion of the therapy to more patients by generating evidence-based strategies that personalize LAAC stroke management based on stroke and bleeding risk.
In terms of real-world evidence for the WATCHMAN FLX Pro device, we also look forward to results from the SURPASS Pro Registry, comparing the WATCHMAN FLX device in the NCDR LAAO Registry to the WATCHMAN FLX Pro device in the same registry. We also anticipate further insights from the HEAL-LAA post-market study for the device, building off the primary endpoint results presented at TCT 2024 which demonstrated consistent complete closure of the LAA and proven safety outcomes in a real-world setting.
Another important study that was recently initiated is the SIMPLAAFY randomized controlled trial, which seeks to assess 2 alternative, single-drug regimens as front-line alternatives to dual antiplatelet therapy (DAPT) following LAAC with the WATCHMAN FLX Pro device in patients with NVAF. It will evaluate whether a less intensive post-implant drug regimen may help further mitigate bleeding risk and provide other viable options for post-implant treatment. Traditionally, after a WATCHMAN implantation, the patient is required to take OAC, DAPT, or a combination of OAC and antiplatelets, for a period of time. Our intention is to prove that the coating on the WATCHMAN FLX Pro device affords the opportunity to minimize that medication regimen and minimize the risk of bleeding during that healing phase after implantation.
These are some of the key studies that are ongoing and that we believe will build upon our strong body of clinical evidence for the WATCHMAN technology, which has been used to treat more than half a million patients worldwide. We remain committed to rigorous investment in science to understand which patients might benefit from the therapy and to get the best procedural and clinical outcomes.
References
1. Boston Scientific data on file.
2. Reddy VY, Gerstenfeld EP, Natale A, et al. Pulsed field or conventional thermal ablation for paroxysmal atrial fibrillation. N Engl J Med. 2023;389(18):1660-1671. doi:10.1056/NEJMoa2307291
3. Hsu JC, Darden D, Du C, et al. Initial findings from the National Cardiovascular Data Registry of Atrial Fibrillation Ablation Procedures. J Am Coll Cardiol. 2023;81(9):867-878. doi:10.1016/j.jacc.2022.11.060
4. Wazni OM, Saliba WI, Nair DG, et al. Left atrial appendage closure after ablation for atrial fibrillation. N Engl J Med. 2024 Nov 16. doi:10.1056/NEJMoa2408308
The transcripts have been edited for clarity and length.
This content was published with support from Boston Scientific.
