Clinical UM Guideline

This document addresses intraluminal left atrial appendage (LAA) closure procedures performed for stroke risk reduction. Several intraluminal occlusion devices have received FDA-approval for LAA closure, including but not limited to: WATCHMAN^™, WATCHMAN FLX^™, WATCHMAN FLX Pro and the Amplatzer Amulet^™ Left Atrial Appendage Occluder devices.

Note: This document does not address extraluminal LAA devices (for example, LARIAT or AtriClip) or surgical LAA ligation or amputation when performed during concomitant open cardiac surgery. For information on LAA excision, exclusion, or occlusion conducted during concurrent cardiac surgery, please refer to the applicable guidelines used by the plan.

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

Medically Necessary:

Closure of the left atrial appendage (LAA) using an intraluminal device is considered medically necessary when all of the following criteria are met:

1. The individual has non-valvular atrial fibrillation; and
2. The procedure is performed for prevention of stroke; and
3. The individual is a candidate for long-term anticoagulation therapy based upon their estimated risk of stroke and other thromboembolic events; and
4. The individual is ineligible for long-term oral anticoagulation therapy (for example, a direct oral anticoagulant [apixaban, dabigatran, edoxaban, or rivaroxaban] or warfarin) due to the presence of contraindication(s) (for example, an increased risk of bleeding), but is expected to be able to tolerate short-term oral anticoagulation necessary for device implantation.

Not Medically Necessary:

Closure of the left atrial appendage (LAA) using an intraluminal device is considered not medically necessary when the criteria above are not met.

This document describes clinical studies and expert recommendations, and explains whether left atrial appendage (LAA) closure (LAAC) or LAA occlusion is appropriate. The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

Intraluminal closure of the LAA is a procedure done to reduce the risk of stroke in people with a common heart rhythm problem called non-valvular atrial fibrillation. The LAA is a small pouch in the wall of the heart where blood clots often form. These clots can travel to the brain and cause a stroke. Intraluminal closure procedures use a small device placed through a catheter (a thin tube) that is passed through the blood vessels into the heart to seal off the LAA. It is typically used in people who are at high risk of stroke but cannot safely take blood thinners long term. Two FDA-approved devices are commonly used for this type of surgery the WATCHMAN (including newer versions like WATCHMAN FLX) and the Amplatzer Amulet. These devices have different designs but work in similar ways. Studies show these procedures can work as well as blood thinners in preventing strokes for certain people and may lead to fewer bleeding problems over time. However, some people still need short-term blood thinners around the time of the procedure. There are also surgical ways to close the LAA, but these are not addressed in this document.

What the Studies Show

Clinical trials have shown that placing a device to close the LAA can work about as well as taking long-term blood thinners for preventing strokes and blood clots in people with non-valvular atrial fibrillation. In some studies, the devices also led to fewer bleeding problems and lower risk of death. These benefits were mostly seen in people who could not take blood thinners long term. Newer versions of these devices, like the WATCHMAN FLX, are safer and easier to place than older ones. There are differences in how the two main devices work and in how often problems like leakage or blood clots around the device occur. For example, the Amulet device may have fewer leaks, but it has been linked to slightly more complications during the procedure. Both devices were found to be similar in effectiveness and safety overall. Large studies and reviews continue to compare them and look at long-term safety.

Some studies also looked at who benefits most from the procedure. People who cannot take blood thinners long term because of bleeding risks are more likely to benefit. Others, especially those who can take blood thinners safely, may not see as much benefit and might even face extra risks from the procedure. Registry data and clinical trials also suggest that women and people from certain racial and ethnic groups may have more complications from the use of these devices. More research is needed to understand and reduce these differences.

When is Intraluminal LAA Closure Clinically Appropriate?

Intraluminal closure of the LAA may be appropriate in these situations:

• The person has non-valvular atrial fibrillation; and
• The procedure is being done to prevent stroke; and
• The person is at increased risk of stroke or blood clots and would normally be a candidate for long-term use of blood thinners; and
• The person cannot safely take long-term blood thinners due to a high risk of bleeding or other medical reasons, but can safely take blood thinners for a short time during and after the procedure.

When is this not Clinically Appropriate?

Intraluminal LAA closure is not clinically appropriate when the above conditions are not met. For example, people who can safely take long-term blood thinners usually do not benefit from the procedure and may face unnecessary risks. Clinical trials show that the procedure is not clearly better than standard treatment with blood thinners in these people.

(Return to Description)

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above when criteria are not met.

Summary:

Intraluminal  left atrial appendage (LAA) closure (LAAC) is a nonpharmacologic strategy to reduce stroke risk in individuals with non-valvular atrial fibrillation (NVAF) by sealing off the LAA, the predominant source of thrombus formation.

The WATCHMAN (Boston Scientific Corp., Maple Grove, MN) and the Amplatzer Amulet Left Atrial Appendage Occluder (Abbott Medical, St. Paul, MN) are LAA closure percutaneous implants that are indicated for individuals with NVAF at increased risk of stroke, who are eligible for short-term anticoagulation but need to seek a nonpharmacologic alternative to long-term oral anticoagulant therapy. Both are catheter-delivered, permanent mesh devices designed to occlude the LAA. The devices have received U.S. Food and Drug Administration approval through the Pre-Market Approval (PMA) pathway. The Amulet features a dual-seal design (lobe and disc) that provides immediate LAA ostial closure, while the WATCHMAN is a single-lobe, parachute-shaped device, with newer-generation versions (WATCHMAN FLX and FLX Pro) engineered to improve conformability, sealing, and procedural safety.

While early devices were associated with higher procedural risks, contemporary devices show improved safety profiles. Comparative trials suggest comparable effectiveness between Amulet and WATCHMAN, with differences primarily in procedural characteristics rather than clinical outcomes. Newer-generation devices such as WATCHMAN FLX and WATCHMAN FLX Pro also have shown improved safety and efficacy profiles. Current guidelines recommend LAAC for individuals with NVAF that are poor candidates for long-term anticoagulation.

Randomized controlled trials and comparative studies have demonstrated that LAAC with either device is non-inferior to warfarin or direct oral anticoagulants for the prevention of ischemic stroke and systemic embolism. Some evidence also suggests reductions in major bleeding events, particularly hemorrhagic stroke, and a potential mortality benefit over long-term anticoagulation in selected individuals.

Discussion:

Intraluminal  closure of an LAA is a treatment strategy that prevents travel of an LAA thrombus out of the LAA in individuals with NVAF. The LAA closure system is introduced in the right atrium and then passed into the left atrium through a PFO or through a puncture hole. The Holmes (2009) randomized non-inferiority trial compared LAA closure using the WATCHMAN LAA Closure Device versus warfarin therapy for prevention of stroke in individuals with AF. The study evaluated efficacy between the interventional group and the warfarin group based upon the primary endpoint of reported cardiovascular death (n=5 vs. n=10), all types of stroke (n=16 vs. n=12), and systemic embolism (n=2 vs. n=0). Researchers reported a higher occurrence of primary safety events in the interventional group compared to the warfarin therapy group; serious adverse events included major bleeding, pericardial effusion and device embolization. The authors concluded:

Thus, our strategy for closing the LAA was non-inferior to warfarin therapy in terms of primary efficacy endpoint of all stroke, cardiovascular death, and systemic embolism. Although there is a higher initial safety event rate for device implantation, adverse events were without long term sequelae for most patients. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation.

A study by Reddy (2011) reported on preliminary outcomes from the Watchman LAA System for Embolic Protection in Patients with AF (PROTECT AF) trial and Continued Access PROTECT AF Registry (CAP Registry). Although with improved procedural experience there was a decline in safety events reported, there remains a higher risk of complications. The FDA granted PMA approval March 2015 for the WATCHMAN LAA Closure Device in individuals with non-valvular AF in facilities equipped for heart surgery as an alternative option to long-term warfarin therapy. According to the manufacturer, Boston Scientific Corporation:

WATCHMAN is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who are at increased risk for stroke and systemic embolism based on CHADS₂ or CHA₂DS₂-VASc scores, are deemed by their physicians to be suitable for warfarin; and have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.

In 2014, Reddy reported long-term outcomes of the PROTECT AF trial. The randomized, multicenter study enrolled 707 participants with nonvalvular AF (NVAF) and at least one additional stroke risk factor (CHADS₂ score greater than or equal to 1) who were randomized 2:1 to undergo LAAC with the WATCHMAN LAA Closure Device (n=463, treatment group) or warfarin therapy (n=244, control group). The trial demonstrated a noninferior rate of cardiovascular death, stroke or systemic embolism, compared with warfarin alone. The authors concluded:

After 3.8 years of follow-up among patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular and all-cause mortality.

A multicenter, randomized, clinical trial PREVAIL assessed safety and efficacy of the WATCHMAN LAA Closure device versus long-term warfarin in individuals with NVAF who had a CHADS₂ score of 2 or more (CHADS₂ score of 1 and another risk factor were eligible) (Holmes, 2014). Exclusion criteria included contraindication to warfarin or aspirin, stroke/transient ischemic attack within the last 90 days, symptomatic carotid disease, PFO or atrial septal defect (ASD), thromboembolism or bleeding. PREVAIL enrolled 407 participants, assigned randomly (2:1 ratio) to the device group (n=269) or control group (n=138). Unlike the PROTECT AF trial the PREVAIL did not demonstrate noninferiority in overall efficacy. The authors report that:

At 18 months, the rate of the first co-primary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (Crl): 0.57 to 1.89]) and did not achieve the pre-specified criteria noninferiority (upper boundary of 95% Crl ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE > 7 days’ post randomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% Crl: -0.0190 to 0.0273], achieving noninferiority. Early safety events occurring in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse events, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% versus 8.7%; p=0.004). Pericardial effusions requiring surgical repair decreasing from 1.6% to 0.4% (p=0.36), although the number of events was small.

LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.

Two RCTs have compared use of the WATCHMAN device for LAA closure in individuals with AF eligible for anticoagulation therapy. The peer-reviewed published literature suggests that the WATCHMAN is associated with an increased periprocedural ischemic stroke risk. There is limited evidence supporting the net benefit of transcatheter closure of an LAA with the WATCHMAN LAA Closure device, in individuals with non-valvular AF who are deemed eligible for systemic anticoagulation. Further studies are needed to determine if the long-term risk of systemic anticoagulation exceeds the periprocedural risk of device implantation.

Reddy (2017) reported final results from the PREVAIL trial and as part of a meta-analysis with PROTECT AF trial followed for 5 years. Participants underwent LAAC with the WATCHMAN or treatment with warfarin. The authors reported results:

For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority) posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p=0.27), as were all-stroke/SE (HR: 0.961; p=0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p=0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p=0.0022; HR: 0.45; p=0.03; HR: 0.59; p=0.027; HR: 0.73; p=0.0003, respectively).

The 2019 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) focused update of the 2014 AHA/ACC/HRS guidelines for the management of atrial fibrillation issued a category IIb (weak) recommendation, indicating “percutaneous LLA occlusion may be considered in individuals with AF at increased risk of stroke who have contraindications to long-term anticoagulation” (January, 2019). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drug/alcohol concomitantly) score is used to assess major bleeding risk factors in individuals with AF being considered for anticoagulation. The CHADS₂ score (congestive heart failure, hypertension, age > 75 years, diabetes mellitus, stroke/transient ischemia attack/thromboembolism) and the CHA₂DS₂-VASc score (congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism [doubled], vascular disease, age 65 to 74 years, sex category) are commonly used for stroke risk stratification in individuals with AF. The authors further concluded:

Oral anticoagulation remains the preferred therapy for stroke prevention for most patients with AF and elevated stroke risk. However, for patients who are poor candidates for long-term oral anticoagulation (because of the propensity for bleeding or poor drug tolerance or adherence), the Watchman device provides an alternative. There are important differences in wording between the FDA approval and the Centers for Medicare & Medicaid Services (CMS) approval. In the FDA approval, the device was restricted to patients who were deemed suitable for long-term warfarin (mirroring the inclusion criteria for enrollment in the clinical trials) but had an appropriate rationale to seek a nonpharmacological alternative to warfarin. Conversely, CMS states that the device is an option for patients who are suitable for short-term warfarin but deemed unable to take long-term oral anticoagulation. CMS has specified that patients should have a CHADS₂ score ≥2 or a CHA₂DS₂-VASc score ≥3 to be considered for the device. A number of unresolved issues remain, including the optimal patient selection and periprocedural antithrombotic regimen.

The current FDA labeling specifies that patients should be deemed suitable for anticoagulation and, in particular, a period of periprocedural anticoagulation. Patients unable to take oral anticoagulation were excluded from the Watchman RCTs [randomized control trial]. However, there is increasing experience outside the United States with LAA closure in oral anticoagulation-ineligible patients using an antiplatelet regimen only, and this is the focus of an ongoing RCT.

Boersma (2019) reported periprocedural, 2-year outcome data from the prospective, multicenter, multinational EWOLUTION registry (Evaluating Real-life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology). Overall safety and efficacy data are presented in a subgroup of participants who are at very high-risk of stroke or bleeding, including those with a history of ischemic and hemorrhagic stroke and those with prior bleeding episodes. In total, 1020 participants (age 73.4 ± 8.9 years) underwent implantation with the WATCHMAN device. While 72 percent of participants were deemed unsuitable for oral anticoagulation by their physicians, data was not readily provided on the reason for contraindication to anticoagulation therapy. At the time of hospital discharge, after successful WATCHMAN placement, 94% of participants were on some form of anticoagulation or antiplatelet drug, and by study-end, 86% were using some form of anticoagulation therapy or antiplatelet drug (8% were using oral anticoagulation, 7% were on dual antiplatelet therapy and 71% were on single antiplatelet therapy). At 2-year follow-up, 16.4% (n=161) of participants that underwent a WATCHMAN LAA had died; 4.5% (n=46) had a cardiovascular reason (most commonly reported was heart failure) and 1% (n=10) were from fatal bleeding (6 were gastrointestinal bleeds while the other 4 were cerebral; only 1 participant was not taking an anticoagulant at time of death). The composite risk of ischemic stroke/TIA/embolic event was 2.0/100 participant-years (46 thromboembolic events in 35 participants, of which 22 were ischemic stroke (5 disabling), 23 were TIA, and one was an systemic embolism), which the authors compare to a historical rate of 10.0/100 participant-years based on CHA₂DS₂-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease 65 to 74 years of age, female; left ventricular ejection fraction) score. In 835 participants with imaging of the LAA, a total of 34 cases of device-related thrombus (4.1%) were observed, resulting in 21 participants initiating treatment, and 1 major GI bleed which resolved. By study-end, resolution occurred in all but 1 participant (6 were lost to followed-up), no subsequent reports of embolic events were reported. Stroke and bleeding rates did not appear to differ by anticoagulation treatment strata, although it is difficult to draw conclusions based on the registry nature of the study. In summary, the study is limited by its registry design; determining the absolute or relative benefit and risks of the WATCHMAN device versus standard treatment in the population studied is unclear given the lack of a randomized comparable prospective treatment arm. A high number of participants enrolled in EWOLUTION also died during the 2 years of follow-up. A majority of individuals also remained on some form of anticoagulation therapy or antiplatelet drug despite being deemed unsuitable for short- or long-term oral anticoagulation at the time of implant, thus continued use of any form of oral anticoagulation or antiplatelet drug may play a role in thromboembolic event prevention.

In June 2020, the FDA approved the next generation WATCHMAN FLX Left Atrial Appendage Closure Device, which is the first device to be fully recapturable for repositioning and redeployment. This generation of the device is available in various sizes and a reduced device length to accommodate a variety of LAA anatomy.

In 2021, Kar published results from the Protection Against Embolism for Nonvalvular AF (NVAF) Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology (PINNACLE FLX) trial. This prospective, nonrandomized, multicenter trial evaluated safety and effectiveness of the WATCHMAN FLX LAA closure device. Eligible participants had NVAF, a CHA₂DS₂-VASc score of ≥ 2 for men or ≥ 3 for women, able to take the postimplant antithrombotic medication, had rationale for a nonpharmacologic stroke prevention, and no comorbid conditions that would require long-term anticoagulation therapy. After placement of the new device, follow-up visits occurred at 45 days, and 6, 12, 18 and 24 months. Participants received directly acting oral anticoagulant (DOAC) treatment and concomitant low dose aspirin through at least the 45-day follow-up appointment. With evidence of an adequate LAA seal (leak ≤ 5 mm) at the 45-day visit, participants were instructed to discontinue DOAC therapy and begin dual antiplatelet therapy with 75 mg of clopidogrel and low-dose aspirin until 6 months after implantation, followed by low-dose aspirin indefinitely. With evidence of a leak > 5 mm, participants continued DOAC therapy plus aspirin and were reevaluated at 6 months post implantation. The primary safety endpoint was the occurrence of death, ischemic stroke, systemic embolism, or device or procedure-related events requiring cardiac surgery within 7 days after the procedure or by hospital discharge. The performance goal established for the primary safety endpoint was 4.21%. For this outcome, the investigators determined that a sample size of 400 individuals would yield 92% or 77% power (1-sided α=0.05 or 2-sided α=0.05, respectively). The primary effectiveness endpoint was incidence of effective LAA closure (peri-device flow ≤ 5 mm), as assessed by the echocardiography core laboratory at the 12-month follow-up visit. The performance goal established for the effectiveness endpoint was 97.0%, and 400 individuals would yield 92% or 81% power (1-sided α=0.05 or 2-sided α=0.05, respectively). A total of 400 individuals were enrolled. The mean age was 73.8 ± 8.6 years, 64.5% were men, and 94% were White. A total of 395 (98.8%) achieved implant procedure success. The incidence of the primary safety end point was 0.5%, with a 2-sided 95% confidence interval (CI) of 1.8%, which was below the performance goal of 4.21% (p<0.0001). The incidence of the primary effective end point of LAA closure was 100%, with a 2-sided 95% CI of 98.9%, above the performance goal of 97.0% (p<0.0001). A total of 7 individuals experienced device-related thrombus. The investigators concluded:

The PINNACLE FLX study results demonstrate that the next-generation LAA closure device, in combination with a 6-week postprocedural regimen of a DOAC and low-dose aspirin, is associated with a low incidence of safety events and high incidence of effective appendage closure.

In 2019, Holmes reported long-term follow-up data from two U.S. FDA LAAC mandated registries (CAP [continued access PROTECT-AF] and CAP2 [continued access PREVAIL]) for safety and efficacy of LAAC for stroke prevention in participants with NVAF. The CAP registry included 566 participants (average follow-up 50.1 months) and CAP2 registry included 578 participants (average follow-up 50.3 months); these registries represent the longest follow-up for participants that have been implanted with the WATCHMAN LAAC Device. The CAP registry enrolled participants who met identical inclusion/exclusion criteria as the original PROTECT-AF RCT; similarly, the CAP2 registry used identical inclusion/exclusion criteria as PREVAIL. Participants had documented paroxysmal, persistent, or permanent non-valvular AF, were eligible for long-term warfarin therapy, had CHADS₂ score of 2 or greater. Individuals with a CHADS₂ score of 1 were included but had to meet additional ACC/AHA/ESC 2006 guidelines for the management of AF for participants requiring warfarin therapy. Notably, both registries excluded warfarin-contraindicated individuals. Participants enrolled in CAP2 were significantly older (≥ 75 years of age) and had higher CHA₂DS₂-VASc scores (4.51 vs. 3.88; p<0.001). In both the CAP and CAP2 the procedural success was similar (94%). In the CAP registry, full 5-year follow-up was completed in 68% of participants; inability to obtain full follow-up was related to mortality, which occurred in 17.8% of participants; initial failure to implant the device, which occurred in 5.7%, loss to follow-up, which occurred in 5.1%, and another 3.5% of participants withdrew permission and consent. At 60 months, 94.8% of participants remained off warfarin.

Similar results were reported in the CAP2 registry, although a higher percent of participants died before follow-up completion (21.8%). The primary composite endpoint - stroke (ischemic and hemorrhagic), cardiovascular death, and systemic embolism - occurred in 12.4% of CAP and 17.6% of CAP2 participants; events contributing to the composite endpoint included mostly cardiovascular death and ischemic stroke. The most frequent adverse event in the CAP registry was gastrointestinal bleeding (5.8%), followed by pericardial effusion with cardiac tamponade (1.2%); device-related thrombus occurred in 2.6% of CAP and 3.9% of CAP2 participants. Given the lack of a comparator arm, it is difficult to assess the long-term effectiveness and safety of the WATCHMAN LAAC device compared to standard of care, particularly direct oral anticoagulant therapy. Furthermore, for participants unable to tolerate long-term anticoagulation, the results of the CAP and CAP2 registries provide no additional data. Both registries were subject to high rates of loss to follow-up (mostly related to mortality), which complicates attempts to compare relative ischemic stroke reductions with expected rates (based on CHA₂DS₂-VASc scores estimated in the absence of therapy).

Cardiovascular outcomes may vary by gender, socioeconomic status, and ethnicity/race. A cross-sectional study by Darden (2021) compared outcomes of males and females who underwent LAAO. Individuals in this study were enrolled in the National Cardiovascular Data LAAO Registry. Outcomes included aborted or canceled procedure (no venous access was performed), major adverse event, any in-hospital adverse event (death, cardiac arrest, ischemic stroke, hemorrhagic stroke, undetermined stroke, TIA, intracranial hemorrhage, systemic arterial embolism, major bleeding, major vascular complication, myocardial infarction, pericardial effusion requiring drainage, and device embolization), and prolonged hospital stay (> 1 day). Multivariate logistic regression was performed to adjust for age, race/ethnicity, body mass index, congestive heart failure, hypertension, type 1 or 2 diabetes, stroke, vascular disease, coronary artery disease, left ventricular ejection fraction, glomerular filtration rate, prior P2Y12 inhibitor or oral anticoagulant prescription, and hospital region. A total of 49,357 individuals were included, of whom 20,388 (41.3%) were natal females. Natal females were more likely than natal males to experience any adverse and major adverse events, had lengths of stays longer than 1 day, and while a rare occurrence, in-hospital death (p<0.001 for all). In addition, Alkhouli (2022) evaluated gender-specific short- and long-term outcomes by gender after LAAO in the Amulet IDE trial. A total of 1833 individuals (1099 males and 734 [40%] females) underwent attempted device implantation (917 with the Amulet and 916 with the WATCHMAN). There were no differences in the rate of implantation success, as well as rates of ischemic stroke, TIA, hemorrhagic stroke, major bleeding, cardiovascular death, or all-cause death between natal males and natal females. However, natal females experienced higher rates of major in-hospital adverse events compared to males (p<0.001) due to pericardial effusions that required intervention and major bleeding (p<0.01 for both). Investigators in both studies indicated that additional research is needed to reduce adverse events in natal females who undergo LAAO implantation.

Diverse populations have not been included in large LAAO trials. In the PROTECT-AF (Reddy 2014), PREVAIL (Homes 2014), and PINNACLE FLX (Kar 2021) trials, most of the populations were White, 91%, 94%, and 94%, respectively. A cross-sectional study by Khan (2021) evaluated differences in clinical characteristics and in-hospital outcomes by race/ethnicity of individuals with AF who underwent WATCHMAN implantation. Data for this study was derived from the National Inpatient Sample database. The study sample was stratified into 4 groups: White, Black, Hispanic, and Other races. Multivariate logistic regression was performed to adjust for age, sex, CHA₂DS₂-VASc score, median income, and 29 Elixhauser comorbidities (Quan 2005). A total of 34,960 individuals were included. Of those, 86% were White, 5.9% Hispanic, 4.2% Black, and 3.7% Other races. Individuals who were Black and Hispanic had higher prevalence rates of heart failure, hypertension, obesity, and renal failure compared to White individuals (p<0.01 for all). After adjusting for confounding factors, individuals who were Black, Hispanic, and Other races, had higher likelihoods of having a major complication from the procedure, and prolonged lengths of stays (> 1 day) compared with White individuals (p<0.01 for both). The investigators concluded that non-white individuals with AF who underwent WATCHMAN implantation had higher rates of select comorbidities and experienced higher WATCHMAN-related adverse events. They also stated that additional research is needed to clarify why these differences exist.

In 2020, Osmancik reported data from the Left Atrial Appendage compared to Novel Anticoagulation Agents in Atrial Fibrillation (PRAGUE-17, NCT02426944) trial. This was a multicenter, prospective, open-label, randomized, non-inferiority that compared LAAC and DOAC in high-risk cohort (CHA₂DS₂-VASc: 4.7± 1.5) with NVAF. The study randomly assigned 402 participants with NVAF to receive DOACs (n=201) or undergo LAAC (n=201). A total of 181 participants (90.0%) had a successful LAAC implantation, 6 participants (3.4%) experienced device-related thrombus. At a median 19.9 months of follow-up, the annual rates of primary outcomes in the LAAC group compared to the DOAC group were 10.99% and 13.42% (the Hazard ratio [HR] CI spanned from 0.53 to 1.31). Between the LAAC and DOAC group there were no differences in stroke/transient ischemic attacks, clinically significant bleeding or cardiovascular death. There were nine major LAAC-related complication that occurred and two procedure and/or device related deaths reported in the LAAC group. In summary, the authors concluded that noninferiority was demonstrated, composite endpoints are challenging to interpret, and components of the composite endpoint were not powered for comparisons.

On August 14, 2021, Abbott received PMA approval for its percutaneous transcatheter device, the Amplatzer^™ Amulet^™ Left Atrial Appendage Occluder  to treat individuals with AF who are at risk of ischemic stroke. The LAA occluder provides a double-seal technology for the complete and immediate sealing of the LAA. The Amulet LAA occluder is intended to reduce the risk of thrombus embolization from the LAA in individuals with NVAF and who are at increased risk for stroke and systemic embolism based on CHADS₂ or CHA₂DS₂-VASc scores, who are suitable for short term anticoagulation therapy, and have appropriate rationale to seek a non-pharmacologic alternative to oral anticoagulation, taking into consideration the safety and effectiveness of the device.

The FDA approval of the Amplatzer Amulet LAA Occluder is based on findings from the Amulet IDE trial (NCT02879448), a multicenter, open label, controlled trial evaluating safety and effectiveness of the Amulet occluder. Lakkireddy and colleges (2021) reported results from the Amulet IDE trial which enrolled 1878 participants who were randomized 1:1 to undergo percutaneous implantation of an LAA occluder with Amulet occluder (n=915) or with the WATCHMAN device (n=916). Eligible participants were 18 years of age or older with documented NVAF (paroxysmal, persistent or permanent) and an increased risk of stroke or systemic embolism (CHADS₂ score ≥ 2 or a CHA₂DS₂-VASc score of ≥ 3). In summary the authors found the Amulet occluder to be noninferior to the WATCHMAN device for the primary safety endpoint (14.5% vs. 14.7%; difference=-0.14; 95% CI, -3.42-3.13; p<0.001 for noninferiority). The Amulet occluder was also noninferior to the WATCHMAN device for primary effectiveness endpoint (2.8% vs. 2.8%; difference=0.00; 95% CI, -1.55-1.55; p<0.001 for noninferiority). The authors stated, “Procedure-related complications were higher with the Amulet device and decreased with operator experience.”

The previously discussed Amulet IDE trial was the largest randomized head-to-head trial that compared the Amulet and Watchman 2.5 LAAO devices. The factors impacting differences in peri-device leak (PDL) rates between the two devices were assessed in a post hoc analysis by Lakkireddy (2023). Of the 1878 participants randomized in the Amulet IDE trial, successful implants occurred in 903 Amulet participants and 885 Watchman participants. An independent lab analyzed images from the protocol-mandated TEE’s at 45 days (801 Amulet, 792 Watchman) and at 12 months (673 Amulet, 618 Watchman), for the presence or absence of severe PDL defined as > 5 mm. The results demonstrated 42 severe PDLs (Amulet 10, Watchman 32). Amulet had fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, p<0.001) and at 12 months (0.1 vs. 1.1%, p<0.001). Larger LAA dimensions were predictors for severe PDL with the Watchman device, however, there were no significant anatomical limitations noted with the Amulet occluder. Furthermore, the majority of Watchman severe PDLs did not resolve over time through 18 months. The authors concluded that the dual-occlusive mechanism (Amulet) demonstrated fewer severe PDLs through 12 months compared with the single-occlusive device (Watchman 2.5).

Jaiswal (2023) published the results of a systematic review and meta-analysis of 3 RCTs that evaluated the safety and clinical outcomes in 150 participants undergoing percutaneous LAA closure with Amplatzer Amulet versus the Watchman device. The mean age was 75 and 76 years in the Amplatzer and the Watchman groups, respectively. The odds of procedure-related complications were higher among participants with Amplatzer compared to the Watchman group (1.80 [95% CI: 1.21-2.67], p<0.001). However, the odds of all-cause mortality (0.75 [95% CI: 0.49-1.16], p=0.20), stroke (0.79 [95% CI: 0.47-1.34], p=0.39), pulmonary embolism (1.34 [95% CI: 0.30-6.04], p=0.70), and major bleeding (1.10 [95% CI: 0.83-1.48], p=0.50) were comparable between the devices. The odds of device related thrombus (0.72 [95% CI: 0.46-1.14], p=0.17) was comparable between both groups, however the incidence of PDLs was lower in the Amulet group (0.41 [95% CI: 0.26-0.66], p<0.001) compared to the Watchman group. The analysis was limited by the fact that some trials included both the 1st generation (Watchman 2.5) as well as 2nd generation (Watchman FLX), which may have impacted results such as the lower incidence of PDLs in the Amulet group. The meta-analysis had minimal-to-low heterogeneity across studies strengthening the results, thus the authors concluded that the Amulet was not superior to the Watchman device in terms of safety and efficacy, however, the Amulet was associated with a higher incidence of procedure-related complications and lower PDL rates. Further large RCTs with longer follow up are needed to examine outcomes such as mortality and stroke.

Najim (2023) completed a meta-analysis that compared the safety and efficacy of the Watchman FLX and the Watchman 2.5 devices from inception to March 2023; 5 studies including 54,727 participants were analyzed. The primary outcome measured was a composite of device thrombosis, device embolism, and major bleeding. Secondary outcomes measured were mortality, stroke, pericardial effusion, and procedural success rate. The analysis demonstrated that the Watchman FLX was associated with increased success (95% CI, 1.98-28.26, p=0.02), and reductions in mortality (95% CI, 0.51-0.54, p<0.01), major bleeding (95% CI, 0.51-0.64, p<0.01), device embolism (95% CI, 0.18-0.70, p=0.02), and pericardial effusion (95% CI, 0.26-0.41, p<0.01). The rates of device-related thrombus and stroke were similar. The authors concluded that the findings indicated improved safety outcomes with the Watchman FLX and favor its use. Additional studies examining the long-term safety outcomes of the device are needed.

Yasmin (2024) completed a systematic review and meta-analysis of 8 studies, with a total of 3408 participants with a median follow-up of 12 months (1897 Watchman, 1511 Amulet). The analysis compared the safety and efficacy of Watchman 2.5 and Amplatzer Amulet devices from inception until June 2023. The safety outcomes evaluated were device success, device-related thrombus, device embolization perioperatively and at follow-up, perioperative pericardial perfusion events, and perioperative cardiac tamponade events. Efficacy outcomes measured were all-cause mortality, cardiovascular mortality at follow-up, stroke, both major and minor bleeding events at follow-up, TIA in the follow-up period, thromboembolic events in the follow-up period, and PDLs in the perioperative period. The data demonstrated that device success was non-significantly reduced in the Watchman group when compared with Amulet (p=0.57), device-related thrombus was non-significantly increased in the Watchman 2.5 group in comparison to Amulet (p=0.11). There were no significant differences between groups in device embolization in the perioperative (p=0.38) and follow up (p=0.13) periods. There were also no significant differences in the risks of pericardial effusion (p=0.98) and cardiac tamponade (p=0.76) perioperatively. Efficacy outcomes showed no significant differences observed in all-cause mortality between devices both perioperatively (p=0.32) and at follow-up (p=0.56). Cardiovascular mortality was non-significantly reduced in the Watchman group compared with Amulet (p=0.20). The Amulet device was not superior to the Watchman device in terms of stroke at follow-up (p=0.63). There was no significant difference in major and minor bleeding events (p=0.63) between the two devices. No difference was observed for TIA (p=0.24) or thromboembolic events (p=0.96) at follow-up. No significant difference was observed between devices for PDLs in the perioperative period (p=0.05). The authors concluded that LAAC is safe and efficacious irrespective of device used, and that Watchman 2.5 is non-superior to Amulet in terms of safety and efficacy.

Ongoing trials include the ASAP-TOO (assessment of the WATCHMAN device in individuals unsuitable for oral anticoagulation) trial, a multicenter prospective randomized trial designed to establish the safety and effectiveness of the WATCHMAN LAAC device in individuals with NVAF that are considered ineligible for oral anticoagulants (NCT02928497); the estimated study completion date is December 2025, to date no results have been published (Holmes, 2017).

Sedaghat (2021) reported findings from the multinational European-Canadian (EUROC)-DRT registry which included individuals in whom a device-related thrombus (DRT) was diagnosed after LAAC during clinical follow-up. While DRT is relatively rare, registry data assessing individuals with DRT suggests that DRT may occur long after LAAC. An analysis of 156 DRT cases from the EUROC-DRT registry found that DRT was detected after a median of 93 days (interquartile range, 54-161 days) with 17.9% being detected > 6 months after LAAC. The authors concluded that “the relevance of DRT after LAAC remains uncertain.”

SCAI’s previously published statements provided an overview of LAAC technology and institutional and operator requirements (2015, 2016). Since then subsequent results from trials and registries have been published, technical expertise and clinical practice has matured, and device and imaging technologies have evolved. In 2023 the SCAI/HRS published a joint Expert Consensus Statement on Transcatheter LAAC that included the following updates:

• Transcatheter LAAC is appropriate for patients with NVAF with high thromboembolic risk who are not suited for long-term oral anticoagulation and who have adequate life expectancy (minimum >1 year) and quality of life to benefit from LAAC. There should be patient-provider discussion for shared decision making.
• Physicians performing LAAC should have a prior experience, including > 50 prior left-sided ablations or structural procedures and > 25 transseptal punctures (TSP). Interventional imaging physicians should have experience in guiding > 25 TSPs before supporting any LAAC procedures independently.
• Technical aspects of the procedure, including venous access, anticoagulation, TSP, delivery sheath selection and placement, left atrial pressure measurement, and device deployment, should be performed in accordance with the labeling of each specific LAAC device.
• Device-related thrombus should be treated with anticoagulation. Repeat imaging at 45- to 90-day intervals can be performed to assess for resolution with eventual cessation of anticoagulation.
• Routine closure of iatrogenic atrial septal defects associated with LAAC should not be performed.
• Patients should be prescribed antithrombotic therapy with warfarin, direct oral anticoagulants, or dual antiplatelet therapy after LAAC according to the studied regimen and instructions for use for each specific device and tailored to the bleeding risks of each patient.
• Combined procedures with LAAC (for example, structural interventions, pulmonary vein isolation) are not routinely recommended, as data are pending from ongoing randomized controlled trials.

Zhang (2024) completed a systematic review to explore the feasibility and safety of LAAC for individuals with LAA thrombus (LAATs). The 26 studies examined included 136 participants with LAATs that had successful LAAC. The Amulet Amplatzer device was most frequently used (48.5%). The majority of procedures adhered to a standard protocol, however, in some cases modifications were made to enhance safety. Among these individuals 77 (56.6%) had absolute contraindications to anticoagulation therapy. Cerebral protection devices were used with 47 participants (34.6%). Warfarin and novel oral anticoagulants were the main medications used prior to the procedure. Dual antiplatelet therapy was primarily used post-procedure. During a mean follow-up period of 13.2 ± 11.5 months, there was 1 case of fatality, 1 case of stroke, 3 major bleeding events, 3 instances of device-related thrombus, and 8 cases of PDLs. The authors concluded that the findings demonstrate preliminary effectiveness and safety of the LAAC procedure in individuals with persistent LAAT. However, future large-scale RCTs with varied LAAT characteristics and LAAC device types are needed to corroborate these findings for decision making in clinical practice.

Maarse (2024) conducted a multicenter cohort study comparing percutaneous LAAO with continued oral anticoagulation therapy (OAT) in individuals with nonvalvular AF who experienced a thromboembolic event despite OAT. Among 433 matched pairs, LAAO was associated with a lower ischemic stroke rate over 2 years (2.8% vs. 8.9% annually; HR, 0.33, p<0.001). After LAAO, 67% discontinued OAT while 33% continued it adjunctively. The authors concluded that LAAO may offer a stroke risk reduction benefit in this high-risk population, however, future RCTs are needed to confirm these findings.

A 2025 international randomized trial evaluated the safety and efficacy of LAAC versus oral anticoagulation in 1600 individuals with AF and elevated stroke risk (CHA₂DS₂-VASc ≥ 2 in men, ≥ 3 in women), who underwent catheter ablation. Participants were randomized 1:1 to LAAC (n=803) or anticoagulation (n=797). At 36 months the primary safety endpoint (non-procedure-related major or clinically relevant nonmajor bleeding) occurred in 8.5% of the LAAC group compared to 18.1% in the anticoagulation group (p<0.001, favoring LAAC), the primary efficacy endpoint (composite of death from any cause, stroke, or systemic embolism) occurred in 5.3% of the LAAC group compared to 5.8% in the anticoagulation group (noninferior, p<0.001), and the secondary endpoint (major bleeding including procedure-related bleeding) occurred in 3.9% (LAAC) compared to. 5.0% (anticoagulation), also meeting noninferiority (p<0.001). Device/procedure-related complications occurred in 23 participants in the LAAC group.

The authors concluded that LAAC is a safe and effective alternative to oral anticoagulation in post-ablation individuals with elevated stroke risk, with significantly lower bleeding risk and noninferior protection against thromboembolic events (Wazni, 2025).

Davis (2025) conducted a meta-analysis of six randomized and comparative clinical trials (n=3666) evaluating LAAC devices, specifically the Watchman and Amplatzer Amulet, either compared directly with each other or versus warfarin or direct oral anticoagulants. The primary analysis compared outcomes between the two LAAC devices, with secondary comparisons to anticoagulation. Primary effectiveness outcomes were any stroke and all-cause mortality. Safety outcomes included any thromboembolism, device embolization, and pericardial effusion. There were no statistically significant differences between Amulet and Watchman in the risk of stroke or all-cause mortality. Similarly, risks of thromboembolism and device embolization did not differ significantly between devices. Compared with warfarin, both LAAC devices were associated with a higher risk of pericardial effusion, with the highest relative risk observed for Amulet (relative risk [RR],27.08; 95% CI: 3.53-207.98), followed by Watchman (RR, 12.79; 95% CI: 1.73-94.85). In direct comparison, Amulet was associated with a significantly higher risk of pericardial effusion than Watchman (RR,  2.12; 95% CI: 1.45-3.09). Overall, the authors concluded that Watchman and Amulet devices demonstrate comparable effectiveness and safety with respect to stroke prevention, mortality, thromboembolism, and device embolization. However, pericardial effusion occurred more frequently with Amulet, which may be relevant for procedural risk stratification and device selection in clinical utilization guidelines.

In conclusion, oral anticoagulation remains the standard of care therapy for stroke prevention for most individuals with AF and elevated stroke risk. Those who are poor candidates for long-term oral anticoagulation may be eligible candidates for LAA Closure Device placement based on observational data, including registry data suggesting improved outcomes as compared to historical controls, in accordance with generally accepted standards of medical practice.

According to the U.S. Centers for Disease Control (CDC) and Prevention, in the U.S., AF is the most prevalent sustained cardiac arrhythmia, resulting in a four- to five-fold greater risk of stroke due to migration of clots that may form in the LAA (CDC, 2020). As confirmed by echocardiography and autopsy, LAA is identified as a leading source of thrombi in individuals with non-valvular AF. By closing off the LAA, the occlusion device is designed to reduce risk of stroke and other cardiovascular complications. The WATCHMAN LAA Closure Device is the first of its kind treatment giving individuals with non-valvular AF an alternative option to long-term warfarin therapy.

CHA₂DS₂-VASc Score: A validated clinical risk stratification tool used to estimate the likelihood of stroke in individuals with atrial fibrillation (Lip, 2011). The acronym reflects the weighted components of the score:

*Note: The gender descriptions used in this document, ‘biological male and ‘biological female’ refer to sex assignment at birth and are used to clarify the cardiovascular risk of the individual, regardless of gender identity or expression.

CHA₂DS₂-VASc scores range from 0 to 9 and are used to estimate relative thromboembolic risk and inform decisions regarding antithrombotic therapy in individuals with atrial fibrillation. Current guidelines divide individuals at risk for ischemic stroke with a CHA2DS2-VASc scores into 3 categories:

• low-risk = 0
• intermediate = 1-2
• high risk ≥ 3

A CHA₂DS₂-VASc score of 1 based on female sex alone is not considered sufficient to warrant anticoagulation. Anticoagulation recommendations typically begin at a CHA₂DS₂-VASc score ≥ 2 for men and ≥ 3 for women (Joglar, 2023).

In 2010, Pisters provides the HAS-BLED bleeding risk score, a practical tool to assess individuals bleeding risk in real-world individuals with AF, supporting clinical decision making regarding antithrombotic therapy in individuals with AF.

Clinical Characteristics Composing the HAS-BLED Bleeding Risk Score

Bleeding is the primary risk associated with systemic anticoagulation. The HAS-BLED bleeding risk score has been developed to estimate the risk of significant bleeding in individuals treated with systemic anticoagulation, which has been validated to assess the annual risk of significant bleeding in individuals with AF treated with warfarin. The score ranges from 0 to 9, based on clinical characteristics, including the presence of hypertension, renal and liver function, history of stroke, bleeding, labile international normalized ratios, age, and drug/alcohol use. Examples of medication usage predisposing to bleeding include clopidogrel or non-steroidal anti-inflammatory drugs. A HAS-BLED score of 3 or greater is considered to be associated with a high risk of bleeding potentially signaling the need for closer monitoring of individuals for adverse risks, closer monitoring of international normalized ratio (INR), or differential dose selections of oral anticoagulants or aspirin.

Atrial fibrillation: A condition where there is disorganized electrical conduction in the atria, resulting in ineffective pumping of blood into the ventricle.

CHADS₂ score: a 5-factor, point-based clinical tool developed to estimate stroke risk in individuals with nonvalvular atrial fibrillation. While historically important and easy to use, it underestimates risk in many individuals because it omits several validated stroke predictors. The CHA₂DS₂-VASc score supplanted CHADS₂ because it improves identification of truly low-risk individuals, provides better discrimination among intermediate-risk individuals, incorporates additional validated risk factors, and is endorsed by contemporary U.S. cardiology guidelines. As a result, CHA₂DS₂-VASc is now the standard tool for stroke risk stratification and anticoagulation decision-making in atrial fibrillation.

Cryptogenic stroke: Cerebral infarction that despite evaluation is not attributable to other well-established singular etiologies including cardioembolism, large artery atherosclerosis, thromboembolism, or small vessel occlusion.

High risk of bleeding: A HAS-BLED score of 3 or greater is considered to be associated with a high risk of potential bleeding in persons requiring anticoagulation.

High risk of stroke: A CHADS₂ score of greater than or equal to 2 or a CHA₂DS₂-VASc score of greater than or equal to 3 are considered high risk of stroke or systemic embolism for individuals with AF.

Intraluminal cardiac device: A medical device that is introduced within the lumen (interior space) of a blood vessel and advanced into the heart, delivered via a transcatheter technique. Such devices are intended to perform a therapeutic or structural function while remaining entirely in direct contact with circulating blood.

Left atrial appendage (LAA): A muscular pouch attached to the upper portion of the left atrium.

Left atrial appendage closure (LAAC): Refers to the result of the occlusion procedure, where the LAA is permanently sealed off. LAAC is intended to reduce the risk of thromboembolism, including ischemic stroke, in individuals with atrial fibrillation by excluding the left atrial appendage (LAA) from systemic circulation, where thrombus formation commonly occurs. LAAC may be performed using percutaneous catheter-based techniques or surgical approaches to cause mechanical and functional isolation of the LAA from the left atrium. The procedure is most often considered in individuals with nonvalvular atrial fibrillation who are at increased stroke risk and have contraindications to long-term oral anticoagulation or seek an alternative to chronic anticoagulant therapy.

Left atrial appendage occlusion (LAAO): Refers to mechanism of blocking blood flow into and out of the left atrial appendage. This can be accomplished by percutaneous or surgical techniques intended to exclude the left atrial appendage from systemic circulation to reduce thromboembolic risk in individuals with atrial fibrillation, which may include endocardial occlusion devices, epicardial ligation, and surgical closure.

Transient Ischemic Attack (TIA): A stroke that lasts only a few minutes. It occurs when the blood supply to part of the brain is briefly interrupted. Symptoms usually occur suddenly and disappear within an hour, although they may persist for up to 24 hours. Symptoms can include numbness or weakness in the face, arm, or leg, especially on one side of the body, trouble seeing in one or both eyes, difficulty with walking, dizziness, confusion or difficulty in talking or understanding speech, loss of balance and coordination (NIH 2024).

Peer Reviewed Publications:

1. Ailawadi G, Gerdisch MW, Harvey RL, et al. Exclusion of the left atrial appendage with a novel device: early results of a multicenter trial. J Thorac Cardiovasc Surg. 2011; 142(5):1002-1009.
2. Alkhouli M, Russo AM, Thaler D, et al. Sex differences in safety and effectiveness of LAAO: insights from the Amulet IDE trial. JACC Cardiovasc Interv. 2022; 15(21):2143-2155.
3. Boersma LV, Ince H, Kische S, et al. Evaluating real-world clinical outcomes in atrial fibrillation patients receiving the WATCHMAN left atrial appendage closure technology. Final 2-year outcome data of the EWOLUTION trial focusing on history of stroke and hemorrhage. Cir Arrhythm Electrophysiol. 2019; 12:e006841.
4. Darden D, Duong T, Du C, et al. Sex differences in procedural outcomes among patients undergoing left atrial appendage occlusion: Insights from the NCDR LAAO registry [published correction appears in JAMA Cardiol. 2021 Oct 20]. JAMA Cardiol. 2021; 6(11):1275-1284.
5. Davis JW, Mai SL, Harmouch W, et al. Comparing effectiveness and safety of left atrial appendage closure devices: a network meta-analysis of randomized controlled trials. Clin Cardiol. 2025; 48(11):e70217.
6. Holmes DR, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation. A patient-level meta-analysis. J Am Coll Cardiol. 2015; 65(24):2614-2623.
7. Holmes DR, Kar S, Price MJ, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol. 2014; 64(1):1-12.
8. Holmes DR, Reddy VY, Buchbinder M, et al. The assessment of the Watchman Device in patients unsuitable for oral anticoagulation (ASAP-TOO) trial. Am Heart J. 2017; 189:68-74.
9. Holmes DR, Reddy VY, Gordon NT, et al. Long-term safety and efficacy in continued access left atrial appendage closure registry. J Am Coll Cardiol. 2019; 74(23): 2878-2889.
10. Holmes DR, Reddy VY, Turi ZG, et al.; PROTECT AF Investigators. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomized non-inferiority trial. Lancet. 2009; 374(9689):534-542.
11. Jaiswal V, Ang SP, Shrestha AB, et al. Amplatzer amulet versus watchman device for percutaneous left atrial appendage closure: a systematic review and meta-analysis. Medicine (Baltimore). 2023;102(26):e34185.
12. Kar S, Doshi SK, Sadhu A, et al. Primary outcome evaluation of a next-generation left atrial appendage closure device: results from the PINNACLE FLX trial. Circulation. 2021; 143(18):1754-1762.
13. Khan MZ, Munir MB, Darden D, et al. Racial disparities in in-hospital adverse events among patients with atrial fibrillation implanted with a Watchman left atrial appendage occlusion device: a US national perspective. Circ Arrhythm Electrophysiol. 2021; 14(5):e009691.
14. Lakkireddy D, Nielsen-Kudsk JE, Windecker S, et al. Mechanisms, predictors, and evolution of severe peri-device leaks with two different left atrial appendage occluders. Europace. 2023; 25(9):euad237.
15. Lakkireddy D, Thaler D, Ellis CR, et al. Amplatzer amulet left atrial appendage occluder versus Watchman device for stroke prophylaxis (Amulet IDE): a randomized, controlled trial. Circulation. 2021; 144(19):1543-1552.
16. Maarse M, Seiffge DJ, Werring DJ, et al. STR-OAC LAAO Group. Left atrial appendage occlusion vs standard of care after ischemic stroke despite anticoagulation. JAMA Neurol. 2024; 81(11):1150-1158.
17. Najim M, Reda Mostafa M, Eid MM, et al. Efficacy and safety of the new generation Watchman FLX device compared to the Watchman 2.5: a systematic review and meta-analysis. Am J Cardiovasc Dis. 2023; 13(5):291-299.
18. Osmancik P, Herman D, Neuzil P, et al. 4-Year outcomes after left atrial appendage closure versus nonwarfarin oral anticoagulation for atrial fibrillation. J Am Coll Cardiol. 2022; 79(1):1-14.
19. Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol. 2020; 75(25): 3122-3135.
20. Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation. The Euro heart survey. Chest. 2010; 138(5):1093-1100.
21. Pisters R, van Köstenberger RJ, Knottnerus ILH, et al. The likelihood of decreasing strokes in atrial fibrillation patients by strict application of guidelines. Europace. 2010; 12(6):779-784.
22. Reddy VY, Doshi SK, Sievert H, et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for embolitic protection in patients with atrial fibrillation) Trial. Stroke. 2013; 127(6):720-729.
23. Reddy VY, Doshi SK, Kar S, et al. 5-Year outcomes after left atrial appendage closure. From the PREVAIL and PROTECT AF trials. J Am Coll Cardiol. 2017; 70(24):2964-2975.
24. Reddy VY, Holmes D, Doshi SK, et al. Safety of percutaneous left atrial appendage closure: results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. 2011; 123(4):417-424.
25. Reddy VY, Mobius-Winkler S, Miller MA, et al. Left atrial appendage closure with the Watchman device in patients with a contraindication for oral anticoagulation: the ASAP study (ASA Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology). J Am Coll Cardiol. 2013; 61(25):2551-2556.
26. Reddy VY, Sievert H, Halperin J, et al. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA. 2014; 312(19):1988-1998.
27. Sedaghat A, Vij V, Al-Kassou B, et al. Device-related thrombus after left atrial appendage closure: data on thrombus characteristics, treatment strategies, and clinical outcomes from the EUROC-DRT-Registry. Circ Cardiovasc Interv. 2021. 14(5):544-553.
28. Yasmin F, Ali E, Moeed A, et al. Safety and efficacy of percutaneous Watchman 2.5 device versus Amplatzer Amulet for left atrial appendage closure in patients with non-valvular atrial fibrillation: a systematic review and study-level meta-analysis. PLoS One. 2024; 19(2):e0295804.
29. Zhang Z, Zhou J, Lin Q, et al. Overcoming barriers for left atrial appendage thrombus: a systematic review of left atrial appendage closure. BMC Cardiovasc Disord. 2024; 24(1):175.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Abbott Medical Devices. AMPLATZER Amulet LAA Occluder trial (Amulet IDE). NLM Identifier: NCT02879448. Last updated February 26, 2025. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02879448?term=NCT02879448&draw=2&rank=1. Accessed on January 28, 2026.
2. Boston Scientific Corporation. Continued access to PREVAIL (CAP2). NLM Identifier: NCT01760291. Last updated on March 29, 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT01760291?term=PREVAIL+WATCHMAN&rank=2. Accessed on January 28, 2026.
3. Boston Scientific Corporation. Evaluation of the WATCHMAN LAA Closure Device in patients with atrial fibrillation versus long term warfarin therapy (PREVAIL). NLM Identifier: NCT01182441. Last updated on July 26, 2018. Available at: https://clinicaltrials.gov/ct2/show/NCT01182441?term=PREVAIL+WATCHMAN&rank=1. Accessed on January 28, 2026.
4. Boston Scientific Corporation. Investigational Device Evaluation of the WATCHMAN FLX™ LAA Closure Technology (PINNACLE FLX). NLM Identifier: NCT02702271. Last updated June 14, 2022. Available at: https://clinicaltrials.gov/ct2/show/NCT02702271. Accessed on January 28, 2026.
5. January CT, Wann S, Alpert JS, et al. 2014 AHA/ACC/HRS practice guideline. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014; 130:e199-e267.
6. January CT, Wann SL, Calkins H, et al. 2019 AHA/ACC/HRS Focused updated of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019; pii: S0735-1097(19)30209-8.
7. Joglar, J, Chung, M. et al. 2023 ACC/AHA/ACCP/HRS Guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol. 2024; 83 (1) 109-279.
8. Lakkireddy D, MD, FACC, University of Kansas Medical Center Research Institute. Safety and Efficacy of Left Atrial Appendage Occlusion Devices. NCT01695564. Last updated May 2, 2019. Available at: http://clinicaltrials.gov/ct2/show/NCT01695564?term=LARIAT&rank=1. Accessed on January 28, 2026.
9. Masoudi FA, Caukins H, Kavinsky CJ, et al. 2015 ACC/HRS/SCAI left atrial appendage occlusion device societal overview: a professional societal overview from the American College of Cardiology, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv. 2015; 86(5):791-807.
10. Saw J, Holmes DR, Cavalcante JL, et al. SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure. JACC Cardiovasc Interv. 2023;16(11):1384-1400.
11. U.S. Food and Drug Administration (FDA) Premarket Notification Database (PMA). Amplatzer^™ Amulet^™ Left Atrial Appendage Occluder. No. P200049. Rockville, MD: FDA. August 14, 2021. Available at: https://www.acessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfi?id=P200049S014. Accessed on January 28, 2026.
12. U.S. Food and Drug Administration (FDA). Premarket Approval (PMA). WATCHMAN Left Atrial Appendage Closure Device with delivery system and WATCHMAN FLX Left Atrial Appendage Closure Device with delivery system. No. P130013/S035. Rockville. MD: FDA. July 21, 2020. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P130013S035. Accessed on January 28, 2026.
13. Wazni OM, Saliba WI, Nair DG, et al. OPTION Trial Investigators. Left atrial appendage closure after ablation for atrial fibrillation. N Engl J Med. 2025; 392(13):1277-1287.

1. Centers for Disease Control and Prevention. Atrial fibrillation. Last updated May 15, 2024. Available at: https://www.cdc.gov/heart-disease/about/atrial-fibrillation.html?CDC_AAref_Val=https://www.cdc.gov/heartdisease/atrial_fibrillation.htm. Accessed on January 28, 2026.

Amulet Left Atrial Appendage Occluder
Left Atrial Appendage (LAA)
Left Atrial Appendage Closure (LAAC)
Left Atrial Appendage Occlusion (LAAO)
WATCHMAN LAA Closure Device
WATCHMAN FLX LAA Closure Device
WATCHMAN FLX Pro LAA Closure Device

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

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