Medical Policy

Policy Num:      07.001.168
Policy Name:    Surgical Left Atrial Appendage Occlusion Devices for Stroke Prevention in Atrial Fibrillation
Policy ID:          [07.001.168]  [Ac / B / M- / P-]  [7.01.172]

Last Review:      September 18, 2024
Next Review:      September 20, 2025
 

Related Policies:
2.002.034 - Percutaneous Left Atrial Appendage Closure Devices for Stroke Prevention in Atrial Fibrillation

Surgical Left Atrial Appendage Occlusion Devices for Stroke Prevention in Atrial Fibrillation

Summary

Description

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Stroke associated with AF is primarily embolic, tends to be more severe than the typical ischemic stroke, and causes higher rates of mortality and disability. As a result, stroke prevention is one of the main goals of AF treatment. Treatment with anticoagulant medications is a first-line approach to stroke prevention in individuals with AF, although occlusion of the left atrial appendage (LAA) may offer a non-pharmacological alternative to anticoagulant medications for those with a contraindication or intolerance to long-term anticoagulant use or with poor anticoagulant adherence. Multiple surgical techniques may be used to excise or occlude the LAA. One device, the AtriClip Left Atrial Appendage Exclusion System, has approval from the U.S. Food and Drug Administration for surgical LAA occlusion for stroke prevention in patients with AF.

Summary of Evidence

For individuals with atrial fibrillation (AF) at increased risk for embolic stroke undergoing left atrial appendage (LAA) occlusion with an AtriClip device concomitant with open or thoracoscopic cardiac surgical procedures, the evidence includes a randomized controlled trial (RCT), a controlled observational study, and case series. Relevant outcomes are ischemic stroke, cardiac events, and mortality. Although evidence from several systematic reviews and a large (N>10,000) observational study found surgical LAA occlusion was associated with a reduction in the risk of stroke without an increase in the risk of adverse events, direct evidence specifically comparing the AtriClip Left Atrial Appendage Exclusion System with anticoagulation, another surgical occlusion method, or no occlusion is limited. LAA occlusion was associated with a reduced risk of stroke versus no occlusion in the Left Atrial Appendage Occlusion Study (LAAOS) III trial, but the trial was not designed to specifically assess the net health benefit of LAA occlusion with an AtriClip device. A retrospective database study that compared the AtriClip device with no occlusion found that AtriClip placement was associated with a lower risk of ischemic stroke, which was not statistically significant, and a reduced risk of thromboembolism that was of marginal statistical significance. Large (N>100) case series of AtriClip device use with 2- to 3-year follow-up reported stroke rates of 1% or fewer in the postoperative period and 2% or fewer in the long-term follow-up. Well-designed RCTs with follow-up of 1 year or more comparing the AtriClip device with anticoagulation, other surgical occlusion methods, and/or no occlusion are needed to provide adequate evidence for assessment of net health benefit. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals with AF at increased risk for embolic stroke undergoing LAA occlusion with an AtriClip device as a stand-alone procedure, the evidence includes a controlled observational study and case series. Relevant outcomes are ischemic stroke, cardiac events, and mortality. One small (N=40) industry-sponsored retrospective observational study reported that use of the AtriClip device as a stand-alone procedure resulted in similar outcomes compared to percutaneous LAA occlusion. This evidence is too limited to draw definitive conclusions. Well-designed RCTs with follow-up of 1 year or more comparing stand-alone AtriClip device placement with percutaneous LAA occlusion are needed to provide adequate evidence for assessment of net health benefit. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Additional Information

Not applicable.

Objective

The objective of this evidence review is to evaluate whether surgical occlusion of the left atrial appendage with an AtriClip device improves the net health outcome in individuals with atrial fibrillation at increased risk for embolic stroke.

Policy Statements

The use of surgical left atrial appendage occlusion devices, including the AtriClip device, for stroke prevention in individuals with atrial fibrillation undergoing open or thoracoscopic cardiac procedures is considered investigational.

The use of surgical left atrial appendage occlusion devices, including the AtriClip device, for stroke prevention as a stand-alone procedure for stroke prevention in individuals with atrial fibrillation is considered investigational.

Policy Guidelines

Coding

See the Codes table for details.

Benefit Application

BlueCard/National Account Issues

State or federal mandates (eg, Federal Employee Program) may dictate that certain U.S. Food and Drug Administration‒approved devices, drugs, or biologics may not be considered investigational, and thus these devices may be assessed only by their medical necessity.

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Atrial Fibrillation

Nonvalvular atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting at least 2.7 million people in the United States. The risk of AF has been found to be lower in Black, Hispanic, and Asian patients relative to White patients, following adjustment for demographic and AF risk factors.^1,2, AF is typically described according to frequency and duration and includes paroxysmal (duration up to 1 week), persistent (>1 week), long-term persistent (>1 year), or permanent (normal sinus rhythm cannot be restored despite treatment).^3, Stroke is the most serious complication of AF. The estimated incidence of stroke in non-treated patients with AF is 5% per year. Despite a lower risk of AF, Black and Hispanic patients have an increased risk of stroke compared with White patients.^4,5, Although this paradox may be partially attributable to clinical factors (e.g., congestive heart failure, hypertension, type 2 diabetes), Black and Hispanic patients with AF are less likely than White patients to receive stroke prevention therapy.^6, Stroke associated with AF is primarily thromboembolic, tends to be more severe than the typical ischemic stroke, and causes higher rates of mortality and disability. As a result, stroke prevention is one of the main goals of AF treatment.

Stroke Prevention

The risk for stroke among patients with AF is evaluated using several factors. Two commonly used scores, the CHADS₂ score and the CHA₂DS₂-VASc score are described in Table 1:

Table 1. CHADS₂ and CHA₂DS₂-VASc Scores to Predict Ischemic Stroke Risk in Patients With Atrial Fibrillation

Adapted from Lip et al (2018)7, and January et al (2014)8,

Stroke in AF occurs primarily as a result of thromboemboli from the left atrium. The erratic atrial contractions in AF lead to blood stasis in the left atrium, and this low flow state increases the risk for thrombosis. The first-line treatment for stroke prevention in AF is long-term anticoagulation, which has proven efficacy.^9, Warfarin, a vitamin K antagonist, is the predominant agent in clinical use. Several newer direct oral anticoagulant (DOAC) agents, including dabigatran, rivaroxaban apixaban, and edoxaban, have received U.S. Food and Drug Administration (FDA) approval for stroke prevention in nonvalvular AF and have demonstrated noninferiority to warfarin in clinical trials. Warfarin requires frequent monitoring and adjustments as well as lifestyle changes; DOACs do not require the frequent monitoring seen with warfarin therapy. While anticoagulation is effective for stroke prevention, it carries an increased risk of bleeding. Reversal agents can be used to counter the effects of life-threatening bleeding in individuals using warfarin or DOAC therapy. Such agents carry their own risk of inducing life-threatening thrombosis. For individuals with AF who have a contraindication to warfarin and DOACs, dual antiplatelet therapy with aspirin and clopidogrel is an option for stroke prevention, though it is less protective than either warfarin or DOACs.

The area of the left atrium with the lowest blood flow in AF, and therefore the highest risk of thrombosis, is the left atrial appendage (LAA). The LAA is a small extension of the left atrium that can vary widely in both size and shape (morphology). LAA morphologies are described according to their appearance and include: the chicken wing, which is the most common morphology and features a prominent bend in the dominant lobe; the cactus, characterized by a dominant central lobe with superior and inferior secondary lobes; the windsock, which features one dominant lobe; and the cauliflower, which is the least common morphology and features numerous lobes with none being dominant. It has been estimated that over 90% of left atrial thrombi occur in the LAA. Surgical removal or exclusion of the LAA is often performed in patients with AF who are undergoing open heart surgery. Surgical techniques to exclude the LAA include resection or occlusion through stapling or clipping.^9,10,

Percutaneous LAA occlusion is discussed in policy 2.02.26.

Regulatory Status

In June 2010, the AtriClip LAA Exclusion System (Atricure) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process (K093679). The FDA determined that this device was substantially equivalent to existing devices for occlusion of the LAA. The AtriClip has gone through numerous iterations since 2010, primarily relating to changes in the clip material composition and refinements of the clip applicator. The current FDA-cleared indication is unchanged from the original 2010 indication, which states that the AtriClip is indicated for "exclusion of the LAA, performed under direct visualization, in conjunction with other cardiac surgical procedures."^11, The FDA clearance documentation notes that direct visualization “requires that the surgeon is able to see the heart directly, with or without assistance from a camera, endoscope, etc. or other appropriate viewing technologies." As of 2022, AtriCure markets 7 different versions of the AtriClip device, whose use varies according to LAA size and type of concomitant surgical procedure.^12,

Rationale

This evidence review was created in June 2022 with a search of the PubMed database. The most recent literature update was performed through June 14 , 2024.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1 

Surgical Left Atrial Appendage Occlusion with the AtriClip Device Concomitant with an Open or Thoracoscopic Cardiac Procedure

Clinical Context and Therapy Purpose

The purpose of surgical left atrial appendage (LAA) occlusion with the AtriClip device in patients with atrial fibrillation (AF) at risk for embolic stroke is to provide a treatment option that is an alternative to or an improvement on existing therapies.

Use of anticoagulants is the first-line therapy for the reduction of the risk of stroke in individuals with AF. Surgical occlusion of the LAA with AtriClip may be a treatment option for those with contraindications or intolerance to anticoagulants, or in those with poor anticoagulant adherence.

The following PICO was used to select literature to inform this review.

Populations

The relevant population(s) of interest are individuals with AF at increased risk for embolic stroke undergoing LAA occlusion concomitant with open or thoracoscopic cardiac surgical procedures.

Interventions

The therapy being considered is surgical LAA occlusion with the AtriClip device.

The efficacy of surgical LAA occlusion performed in conjunction with other cardiac procedures has been assessed in several systematic reviews and a large (N>10,000) observational study, which have generally found surgical LAA occlusion to be associated with a reduction in the risk of stroke or systemic embolism without an increased risk of post-procedural complications.^13,14,15,16, This review focuses on surgical LAA occlusion with AtriClip. This review does not consider the net health benefit of surgical LAA occlusion in general, nor does it address the net health benefit of surgical LAA occlusion techniques other than AtriClip placement.

Comparators

The following therapies are currently being used for the prevention of stroke in individuals with AF at increased risk for embolic stroke: anticoagulation therapy, other surgical LAA occlusion methods, and no occlusion.

Warfarin is the predominant anticoagulant agent in clinical use. Several newer anticoagulant medications, including dabigatran, rivaroxaban apixaban, and edoxaban have received U.S. Food and Drug Administration (FDA) approval for stroke prevention in nonvalvular AF and have demonstrated noninferiority to warfarin in clinical trials. Warfarin requires frequent monitoring and adjustments as well as lifestyle changes; direct oral anticoagulants (DOACs) do not require the frequent monitoring seen with warfarin therapy. While anticoagulation is effective for stroke prevention, it carries an increased risk of bleeding. Reversal agents can be used to counter the effects of life-threatening bleeding in individuals using warfarin or DOAC therapy. Such agents carry their own risk of inducing life-threatening thrombosis.

Surgical LAA occlusion methods other than the AtriClip device include epicardial stapling and excision and suture closure.

Outcomes

The general outcomes of interest are overall survival, morbid events, and treatment-related morbidity. The primary outcome of interest is the rate of ischemic stroke during follow-up, along with rates of systemic embolization, cardiac events, and mortality. Surgical success, defined as complete LAA occlusion, is not a direct health outcome, although evidence on surgical success is reported here as incomplete LAA occlusion, which may be associated with an increased risk of stroke.^17,

Follow-up of 6 to 12 months or longer is required to assess outcomes.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

A number of studies were excluded from this evidence review because they did not specifically assess surgical LAA occlusion with the Atriclip device.^{18,19,16,20,21,22,23,24,25,26,}

Systematic Reviews

Toale et al (2019)^27, conducted a systematic review assessing outcomes of LAA occlusion using the AtriClip device in individuals with AF either as a concomitant or stand-alone procedure. The review included 11 uncontrolled cohort studies and case series with a total population of 922 individuals (n ranged from 5 to 291; median n=40). Follow-up among the included studies ranged from time of hospital discharge to 4 years (median 1 year). Results from the largest studies (N>100) with the longest duration (>1 year) are discussed below (see Case Series section). The review found a surgical success rate of 97.8% (902/922) based on varying methods of assessing occlusion completion. When stratified according to surgical approach, success rates were slightly lower for AtriClip placement via a thoracoscopic approach (4 studies; 95.3%) than for an open approach (7 studies; 99.2%). This difference was statistically significant (p=.0002). At least one of the thoracoscopic studies^28, attributed their lower success rate to a learning curve associated with AtriClip placement (see Case Series, below). Within the 30-day postoperative period, 20 individuals underwent surgical revision due to bleeding, 4 had a postoperative ischemic stroke and there were 29 deaths. In follow-up greater than 6 months, there were 5 cases of ischemic stroke, and 42 deaths. Among 798 individuals with data, 477 (60%) had discontinued anticoagulant use.

Randomized Controlled Trials

Whitlock et al (2021)^29, reported the results of The Left Atrial Appendage Occlusion Study (LAAOS) III that randomized 4,811 individuals to LAA occlusion or no occlusion scheduled to undergo cardiac surgery (Table 2). Following post-randomization exclusions prior to surgery, 2,379 individuals were included in the occlusion group and 2,411 were included in the no occlusion group (N=4,770). Demographic and clinical characteristics for the intervention and control groups were similar at baseline. Indications for cardiac surgery included isolated coronary artery bypass graft (CABG; 21%), isolated valve replacement (23%), or other cardiac surgical procedures (55%). Thirty-three percent of the enrolled population underwent surgical ablation for AF. Data on occlusion method were reported for 71% (1,685/2,379) of those randomized to the occlusion group. Occlusion method was selected by the treating surgeon. Among those with data regarding the occlusion method, 15% underwent LAA occlusion with an epicardial closure device (e.g., AtriClip). The primary outcome was the incidence of ischemic stroke or systemic arterial embolism. The results of the trial are summarized in Table 3. At a mean 3.8 years follow-up, occlusion was associated with a significant reduction in risk of the primary outcome when compared with no occlusion, without an increased risk of post-procedural bleeding or mortality. Occlusion appeared to result in greater risk reduction among those using either DOAC (hazard ratio [HR], 0.54; 95% CI, 0.34 to 0.86) or vitamin K antagonist therapy (HR, 0.62; 95% CI, 0.39 to 1.00) at baseline than in those not on anticoagulant therapy (HR, 0.79; 95% CI, 0.56 to 1.12). Anticoagulant use was 83% in the occlusion group and 81% in the no occlusion group at the time of hospital discharge, and the majority of study participants in both groups continued to use anticoagulants at 1- (80% and 79%), 2- (77% and 78%), and 3-year follow-up (75% and 78%). There was no subgroup analysis by occlusion method. Reporting of harms after the perioperative period was limited, but the risk of a major bleeding event (HR, 0.93; 95% CI, 0.78 to 1.11), hospitalization for heart failure (HR, 1.13; 95% CI, 0.92 to 1.40), and myocardial infarction (HR, 0.82; 95% CI, 0.57 to 1.18) were similar between occlusion and no occlusion groups.

Table 2. Summary of Key RCT Characteristics

AF: atrial fibrillation; DOAC: direct-acting oral anticoagulant; LAA: left atrial appendage; NR: not reported; RCT: randomized controlled trial.a Data on occlusion method were reported for 1,685 (of 2,379) study participants

Table 3. Summary of Key RCT Results

CI: confidence interval; HR: hazard ratio; RCT: randomized controlled trial; RR: relative risk.a Reoperation within 48 hours of initial surgery

Study relevance and design and conduct limitations are summarized in Tables 4 and 5. The purpose of the study limitations tables is to display notable limitations identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of evidence supporting the position statement.

The LAAOS III trial had some other important limitations not captured in Tables 4 and 5. Only 15% underwent LAA occlusion with an epicardial closure device (e.g., AtriClip). No subgroup analysis was conducted according to occlusion method. According to the study's authors, this was due to the lack of randomization for occlusion method. Consequently, the study authors noted "we cannot discern from our results whether all surgical closure methods are comparable" and no conclusions about the effectiveness of AtriClip placement relative to other occlusion methods can be drawn from the trial. In addition, due to the lack of an anticoagulant control group, no conclusions can be drawn from the trial about the comparative effectiveness of AtriClip versus first-line therapy (anticoagulants). The fact that 75% or more of study participants were still using anticoagulants up to 3 years following LAA occlusion also limits the applicability of the study results for those individuals with AF and a contraindication to anticoagulant use.

Table 4. Study Relevance Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment. a Population key: 1. Intended use population unclear; 2. Study population is unclear; 3. Study population not representative of intended use; 4, Enrolled populations do not reflect relevant diversity; 5. Other.b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest (e.g., proposed as an adjunct but not tested as such); 5: Other.c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively; 5. Other.d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. Incomplete reporting of harms; 4. Not establish and validated measurements; 5. Clinically significant difference not prespecified; 6. Clinically significant difference not supported; 7. Other.e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms; 3. Other.

Table 5. Study Design and Conduct Limitations

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias; 5. Other.b Blinding key: 1. Participants or study staff not blinded; 2. Outcome assessors not blinded; 3. Outcome assessed by treating physician; 4. Other.c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication; 4. Other.d Data Completeness key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials); 7. Other.e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference; 4. Other.f Statistical key: 1. Analysis is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Analysis is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4. Comparative treatment effects not calculated; 5. Other.

The AtriClip® Left Atrial Appendage Exclusion Concomitant to Structural Heart Procedures (ATLAS) RCT compared the AtriClip device (n=376) with medical management (standard of care anticoagulant therapy; n=186) in individuals undergoing a valve or CABG procedure.^30, The study population did not have a history of AF, but had CHA₂DS₂-VASc of 2 or more (mean score, 3.4). The study completion date was June 2019. Full study results have not been published, but some 1 year results have been reported on ClinicalTrials.gov. Rates of postoperative AF were similar between AtriClip (47.3%) and medical management (40.3%) groups. Rates were also similar between groups (8.5% vs. 8.6%) for a composite outcome that included thromboembolic and hemorrhagic events (e.g., ischemic or hemorrhagic stroke, transient ischemic attack [TIA], peripheral ischemia, bleeding event). The rate of all-cause mortality in the AtriClip group (5.32%) was more than double that in the medical management group (2.15%). Full publication of these results would provide direct evidence on the effectiveness of AtriClip versus standard of care management with anticoagulation therapy.

Nonrandomized Studies

A retrospective database study conducted by Soltesz et al (2021)^31, compared outcomes in 931 Medicare patients who underwent concomitant CABG and LAA occlusion with AtriClip with 3,279 patients who underwent CABG only without AtriClip placement (Table 6). The study was funded by the AtriClip manufacuter and was designed to assess both health outcomes and resource utilization. Anticoagulant use was not reported and it is unclear if baseline use was similar between the 2 groups. Surgical LAA occlusion with AtriClip was associated with a lower risk of thromboembolism, and a nonsignificant reduction in risk of ischemic stroke. There was no difference between AtriClip occlusion and no occlusion groups in post-surgical mortality (≤90 days), but LAA occlusion with AtriClip was associated with a lower risk of death at 90 days or more post-surgery (Table 7).

Table 6. Summary of Key Observational Comparative Studies

AF: atrial fibrillation; CABG: coronary artery bypass graft; LAA: left atrial appendage.

Table 7. Summary of Key Observational Comparative Study Results

CI: confidence interval; HR: hazard ratio; NR: not reported; sHR: subhazard ratioa Proportions represent annual risk, not absolute event rates

Case Series

As noted above, the 2019 Toale et al^27, systematic review included 11 uncontrolled cohort studies or case series of AtriClip placement either as a concomitant or stand-alone procedure. Of the 11 studies in the review, 2 studies^32,33, included more than 100 individuals who had AtriClip placement concomitant to cardiac surgery with follow-up of a year or more (Table 8). Both studies found AtriClip placement associated with successful occlusion rates of 98% or greater and stroke rates of 1% or fewer in the postoperative period and 2% or fewer in the long-term follow-up (Table 9). Kurfirst et al (2017)^33, attributed their less than 100% success rate to a learning curve associated with AtriClip placement; 2 of the 3 failures were among the first 10 cases receiving AtriClip placement. An additional case series published by Heijden et al (2022) was identified, which included 119 individuals with AF treated by minimally invasive thoracoscopic epicardial ablation; the majority of patients were occluded with Atriclip (n=103; 90%), but the remaining patients were occluded with a different device (Lariat, Watchman, or stapler) or were not occluded due to complications.^34, No stroke or mortality occurred post-operatively or through 2 years of follow-up (Table 9).

Table 8. Summary of Key Case Series Characteristics

AF: atrial fibrillation; CABG: coronary artery bypass graft; DOAC: direct-acting oral anticoagulants; NR: not reported.a 4.5% (7/155) underwent AtriClip placement as a stand-alone procedureb A minority of the patients (10%) utilized an occlusion device other than Atriclip. These devices includedincluded: Lariat (n=4), stapler (n=2), Watchman device (n=6) and no closure due to complications (n=5).

Table 9. Summary of Key Case Series Results

NR: not reported.

Section Summary: Surgical Left Atrial Appendage Occlusion with the AtriClip Device Concomitant With an Open or Thoracoscopic Cardiac Procedure

Evidence comparing surgical LAA occlusion with an AtriClip device with anticoagulation, another surgical occlusion method, or no occlusion in individuals undergoing concomitant cardiac procedures is limited. LAA occlusion was associated with a reduced risk of stroke versus no occlusion in the LAAOS III trial, but the trial was not designed to assess the net health benefit of LAA occlusion with an AtriClip device specifically, nor was it designed to assess whether surgical LAA occlusion is suitable as a replacement for long-term anticoagulant use. An industry-sponsored retrospective database study that compared LAA occlusion with AtriClip with no occlusion found that AtriClip placement was associated with a lower risk of ischemic stroke that was not statistically significant, and a reduced risk of thromboembolism that was of marginal statistical significance. Large (N>100) case series with 2- to 3- years follow-up reported stroke rates 1% or fewer in the postoperative period and 2% or fewer in the long-term follow-up. Well-designed RCTs with follow-up of 1 year or more comparing AtriClip with anticoagulation, another surgical occlusion method, and/or no occlusion are needed to provide adequate evidence for assessment of net health benefit.

Population Reference No. 2 

Surgical Left Atrial Appendage Occlusion with the AtriClip Device as a Stand-Alone Procedure

Clinical Context and Therapy Purpose

The purpose of surgical LAA occlusion with AtriClip in patients with AF at risk for embolic stroke is to provide a treatment option that is an alternative to or an improvement on existing therapies.

As noted above, use of anticoagulants is the first-line therapy for the reduction of the risk of stroke in individuals with AF. Surgical occlusion of the LAA with AtriClip may be a treatment option for those with contraindications or intolerance to anticoagulants, or in those with poor anticoagulant adherence.

The following PICO was used to select literature to inform this review.

Populations

The relevant population(s) of interest are individuals with AF at increased risk for embolic stroke undergoing LAA occlusion as a stand-alone procedure.

Interventions

The therapy being considered is surgical LAA occlusion with the AtriClip device.

The efficacy of surgical LAA occlusion performed in conjunction with other cardiac procedures has been assessed in several systematic reviews and a large (N>10,000) observational study, which have generally found surgical LAA occlusion to be associated with a reduction in the risk of stroke or systemic embolism without an increased risk of post-procedural complications.^13,14,15,16, This review focuses on surgical LAA occlusion with AtriClip. This review does not consider the net health benefit of surgical LAA occlusion in general, nor does it address the net health benefit of surgical LAA occlusion techniques other than AtriClip placement.

Comparators

The following therapies are currently being used for the prevention of stroke in individuals with AF at increased risk for embolic stroke: anticoagulation therapy or percutaneous LAA occlusion.

Warfarin is the predominant anticoagulant agent in clinical use. Several newer anticoagulant medications, including dabigatran, rivaroxaban apixaban, and edoxaban have received U.S. FDA approval for stroke prevention in nonvalvular AF and have demonstrated noninferiority to warfarin in clinical trials. Warfarin requires frequent monitoring and adjustments as well as lifestyle changes; DOACs do not require the frequent monitoring seen with warfarin therapy. While anticoagulation is effective for stroke prevention, it carries an increased risk of bleeding. Reversal agents can be used to counter the effects of life-threatening bleeding in individuals using warfarin or DOAC therapy. Such agents carry their own risk of inducing life-threatening thrombosis.

Percutaneous LAA occlusion devices have been developed as a nonpharmacologic alternative for stroke prevention in AF. These devices are delivered through a catheter guided by transesophageal echocardiography or fluoroscopy. Percutaneous LAA occlusion requires the use of anticoagulation therapy during the perioperative period, followed by antiplatelet therapy. Percutaneous LAA occlusion devices are further discussed in policy 2.02.26.

Outcomes

The general outcomes of interest are overall survival, morbid events, and treatment-related morbidity. The primary outcome of interest is the rate of ischemic stroke during follow-up, along with rates of systemic embolization, cardiac events, and mortality. Surgical success, defined as complete LAA occlusion, is not a direct health outcome, although evidence on surgical success is reported here as incomplete LAA occlusion may be associated with an increased risk of stroke.^17,

Follow-up of 6 to 12 months or longer is required to assess outcomes.

Study Selection Criteria

Methodologically credible studies were selected using the following principles:

• To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

• In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

• To assess long-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

• Consistent with a 'best available evidence approach,' within each category of study design, studies with larger sample sizes and longer durations were sought.

• Studies with duplicative or overlapping populations were excluded.

Review of Evidence

Nonrandomized Studies

Branzoli et al (2022)^35, conducted a retrospective cohort study of 40 individuals with AF and a contraindication to anticoagulant use managed by a Heart Team. Participants had a mean age of 74 years, 35% were female and had a mean CHA₂DS₂VASc score of 5.1 at baseline. Between 2017 and 2020, 20 individuals underwent surgical (thoracoscopic) LAA occlusion with the AtriClip device and 20 received percutaneuous LAA occlusion with the Watchman device. Perioperative outcomes (procedure duration, length of hospital stay) were similar between groups with no serious adverse events or deaths. At a mean follow-up of 33 months, there were no instances of hospitalization due to cardiovascular or neurological events in either group.

Case Series

Cartledge et al (2022),^36, and Franciulli et al (2020)^37, reported on the use of AtriClip as a stand-alone LAA occlusion procedure in individuals at high-risk of stroke (Table 10). In both studies, AtriClip placement was achieved via a thoracoscopic approach. LAA occlusion was successful in nearly all cases, with few post-procedural events. No incidence of stroke was reported in either study after 6-months or 1-year follow-up (Table 11). There were 6 deaths in the Cartledge et al study after 1 year, but the study authors deemed none device or procedure related.

Table 10. Summary of Key Case Series Characteristics

AF: atrial fibrillation; TIA: transient ischemic attack

Table 11. Summary of Key Case Series Results

NR: not reported

Section Summary: Surgical Left Atrial Appendage Occlusion with the AtriClip Device as a Stand-Alone Procedure

Evidence on surgical LAA occlusion with the AtriClip device as a stand-alone procedure is limited. One small (N=40) retrospective observational study found use of AtriClip as a stand-alone procedure resulted in similar outcomes as percutaneous LAA occlusion; the evidence is too limited to draw definitive conclusions. Well-designed RCTs with follow-up of 1 year or more comparing AtriClip LAA occlusion with anticoagulants or percutaneous LAA occlusion are needed to provide adequate evidence for the assessment of net health benefit. The ongoing SALAMANDER study (NCT05144958; completion anticipated in 2025) should provide direct comparative evidence of stand-alone AtriClip LAA occlusion with percutaneous occlusion when published.

Supplemental Information

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Practice Guidelines and Position Statements

Guidelines or position statements will be considered for inclusion in ‘Supplemental Information' if they were issued by, or jointly by, a US professional society, an international society with US representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

American Heart Association et al

In 2023, the American Heart Association, in conjunction with the American College of Cardiology, the American College of Clinical Pharmacy, and the Heart Rhythm Society, issued a joint guideline on the management of individuals with atrial fibrillation (AF).^38, The following are the recommendations provided on performing LAAC for patients undergoing cardiac surgery:

• In patients with AF undergoing cardiac surgery with a CHA₂DS₂-VASc score ≥2 or equivalent stroke risk, surgical LAA exclusion, in addition to continued anti-coagulation, is indicated to reduce the risk of stroke and systemic embolism. (Class of recommendation I: Level of evidence: A)

• In patients with AF undergoing cardiac surgery and LAA exclusion, a surgical technique resulting in the absence of flow across the suture line and a stump of <1 cm as determined by intraoperative trans-esophageal echocardiography should be used. (Class of recommendation I: Level of evidence: A)

• In patients with AF undergoing cardiac surgery with CHA₂DS₂-VASc score ≥2 or equivalent stroke risk, the benefit of surgical LAA exclusion in the absence of continued anticoagulation to reduce the risk of stroke and systemic embolism is uncertain. (Class of recommendation IIb: Level of evidence: A)

No recommendation was made regarding the method of surgical LAA occlusion.

Society for Cardiovascular Angiography & Interventions et al

In 2023, the Society for Cardiovascular Angiography & Interventions (SCAI) and Heart Rhythm Society (HRS) issued a consensus statement on transcatheter endovascular left atrial appendage closure (LAAC).^39, The following are the recommendations on patient selection and physician experience prior to receiving or performing LAAC:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation 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 or more prior left-sided ablations or structural procedures and 25 or more transseptal punctures (TSPs). Interventional imaging physicians should have experience in guiding 25 or more TSPs before supporting any LAAC procedures independently.

No recommendation was made regarding the method of surgical LAA occlusion.

American College of Chest Physicians

Guidance from the American College of Chest Physicians in 2018^7, recommends:

• In patients with AF at high risk of ischemic stroke who have absolute contraindications for oral anticoagulants (OAC), we suggest using LAA occlusion (weak recommendation, low quality evidence).
• In AF patients at risk of ischemic stroke undergoing cardiac surgery, we suggest considering surgical exclusion of the LAA for stroke prevention, but the need for long-term OAC is unchanged (weak recommendation, low quality evidence).

No guideline statement recommends a specific occlusion method or approach.

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force (USPSTF) recommendations for surgical LAA occlusion have been identified.

Medicare National Coverage

There is no national coverage determination. In the absence of a national coverage determination, coverage decisions are left to the discretion of local Medicare carriers.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 12.

Table 12. Summary of Key Trials

NCT: national clinical trial.a Denotes industry-sponsored or cosponsored trial.

References

1. Dewland TA, Olgin JE, Vittinghoff E, et al. Incident atrial fibrillation among Asians, Hispanics, blacks, and whites. Circulation. Dec 03 2013; 128(23): 2470-7. PMID 24103419
2. Mou L, Norby FL, Chen LY, et al. Lifetime Risk of Atrial Fibrillation by Race and Socioeconomic Status: ARIC Study (Atherosclerosis Risk in Communities). Circ Arrhythm Electrophysiol. Jul 2018; 11(7): e006350. PMID 30002066
3. Nesheiwat Z, Goyal A, Jagtap M. Atrial Fibrillation. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 28, 2021.
4. Gardener H, Sacco RL, Rundek T, et al. Race and Ethnic Disparities in Stroke Incidence in the Northern Manhattan Study. Stroke. Apr 2020; 51(4): 1064-1069. PMID 32078475
5. Guo J, Gabriel N, Magnani JW, et al. Racial and Urban-Rural Difference in the Frequency of Ischemic Stroke as Initial Manifestation of Atrial Fibrillation. Front Public Health. 2021; 9: 780185. PMID 34805085
6. Tamirisa KP, Al-Khatib SM, Mohanty S, et al. Racial and Ethnic Differences in the Management of Atrial Fibrillation. CJC Open. Dec 2021; 3(12 Suppl): S137-S148. PMID 34993443
7. Lip GYH, Banerjee A, Boriani G, et al. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report. Chest. Nov 2018; 154(5): 1121-1201. PMID 30144419
8. January CT, Wann LS, Alpert JS, et al. 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. Dec 02 2014; 64(21): e1-76. PMID 24685669
9. Collado FMS, Lama von Buchwald CM, Anderson CK, et al. Left Atrial Appendage Occlusion for Stroke Prevention in Nonvalvular Atrial Fibrillation. J Am Heart Assoc. Nov 02 2021; 10(21): e022274. PMID 34668395
10. Rosati F, de Maat GE, Valente MAE, et al. Surgical clip closure of the left atrial appendage. J Cardiovasc Electrophysiol. Oct 2021; 32(10): 2865-2872. PMID 34288215
11. U.S. Food and Drug Administration. AtriClip LAA Exclusion System (K172742). https://www.accessdata.fda.gov/cdrh_docs/pdf17/K172742. Accessed June 14, 2024.
12. AtriCure. AtriClip LAA Exclusion System. https://www.atricure.com/healthcare-professionals/therapies/LAAM/atriclip-exclusion-system. Accessed June 14, 2024.
13. Ando M, Funamoto M, Cameron DE, et al. Concomitant surgical closure of left atrial appendage: A systematic review and meta-analysis. J Thorac Cardiovasc Surg. Sep 2018; 156(3): 1071-1080.e2. PMID 29628346
14. Atti V, Anantha-Narayanan M, Turagam MK, et al. Surgical left atrial appendage occlusion during cardiac surgery: A systematic review and meta-analysis. World J Cardiol. Nov 26 2018; 10(11): 242-249. PMID 30510641
15. Ibrahim AM, Tandan N, Koester C, et al. Meta-Analysis Evaluating Outcomes of Surgical Left Atrial Appendage Occlusion During Cardiac Surgery. Am J Cardiol. Oct 15 2019; 124(8): 1218-1225. PMID 31474327
16. Friedman DJ, Piccini JP, Wang T, et al. Association Between Left Atrial Appendage Occlusion and Readmission for Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant Cardiac Surgery. JAMA. Jan 23 2018; 319(4): 365-374. PMID 29362794
17. Aryana A, Singh SK, Singh SM, et al. Association between incomplete surgical ligation of left atrial appendage and stroke and systemic embolization. Heart Rhythm. Jul 2015; 12(7): 1431-7. PMID 25998141
18. Abrich VA, Narichania AD, Love WT, et al. Left atrial appendage exclusion during mitral valve surgery and stroke in atrial fibrillation. J Interv Card Electrophysiol. Dec 2018; 53(3): 285-292. PMID 30267182
19. Blackshear JL, Johnson WD, Odell JA, et al. Thoracoscopic extracardiac obliteration of the left atrial appendage for stroke risk reduction in atrial fibrillation. J Am Coll Cardiol. Oct 01 2003; 42(7): 1249-52. PMID 14522490
20. Fu M, Qin Z, Zheng S, et al. Thoracoscopic Left Atrial Appendage Occlusion for Stroke Prevention Compared with Long-Term Warfarin Therapy in Patients With Nonvalvular Atrial Fibrillation. Am J Cardiol. Jan 01 2019; 123(1): 50-56. PMID 30385030
21. Inoue T, Suematsu Y. Left atrial appendage resection can be performed minimally invasively with good clinical and echocardiographic outcomes without any severe risk. Eur J Cardiothorac Surg. Jul 01 2018; 54(1): 78-83. PMID 29370349
22. Jiang S, Zhang H, Wei S, et al. Left atrial appendage exclusion is effective in reducing postoperative stroke after mitral valve replacement. J Card Surg. Dec 2020; 35(12): 3395-3402. PMID 32939788
23. Kewcharoen J, Shah K, Bhardwaj R, et al. Surgical left atrial appendage occlusion in patients with left ventricular assist device. Pacing Clin Electrophysiol. Apr 2022; 45(4): 567-570. PMID 35199863
24. Ohtsuka T, Nonaka T, Hisagi M, et al. Thoracoscopic stapler-and-loop technique for left atrial appendage closure in nonvalvular atrial fibrillation: Mid-term outcomes in 201 patients. Heart Rhythm. Sep 2018; 15(9): 1314-1320. PMID 29803851
25. Park-Hansen J, Holme SJV, Irmukhamedov A, et al. Adding left atrial appendage closure to open heart surgery provides protection from ischemic brain injury six years after surgery independently of atrial fibrillation history: the LAACS randomized study. J Cardiothorac Surg. May 23 2018; 13(1): 53. PMID 29792215
26. Yao X, Gersh BJ, Holmes DR, et al. Association of Surgical Left Atrial Appendage Occlusion With Subsequent Stroke and Mortality Among Patients Undergoing Cardiac Surgery. JAMA. May 22 2018; 319(20): 2116-2126. PMID 29800182
27. Toale C, Fitzmaurice GJ, Eaton D, et al. Outcomes of left atrial appendage occlusion using the AtriClip device: a systematic review. Interact Cardiovasc Thorac Surg. Nov 01 2019; 29(5): 655-662. PMID 31292605
28. Kurfirst V, Mokrácek A, Canádyová J, et al. Epicardial clip occlusion of the left atrial appendage during cardiac surgery provides optimal surgical results and long-term stability. Interact Cardiovasc Thorac Surg. Jul 01 2017; 25(1): 37-40. PMID 28369643
29. Whitlock RP, Belley-Cote EP, Paparella D, et al. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. N Engl J Med. Jun 03 2021; 384(22): 2081-2091. PMID 33999547
30. AtriClip Left Atrial Appendage Exclusion Concomitant to Structural Heart Procedures (ATLAS). https://clinicaltrials.gov/ct2/show/NCT02701062. Accessed June 14, 2024.
31. Soltesz EG, Dewan KC, Anderson LH, et al. Improved outcomes in CABG patients with atrial fibrillation associated with surgical left atrial appendage exclusion. J Card Surg. Apr 2021; 36(4): 1201-1208. PMID 33491275
32. Caliskan E, Sahin A, Yilmaz M, et al. Epicardial left atrial appendage AtriClip occlusion reduces the incidence of stroke in patients with atrial fibrillation undergoing cardiac surgery. Europace. Jul 01 2018; 20(7): e105-e114. PMID 29016813
33. Kurfirst V, Mokracek A, Canadyova J, et al. Effectivity of Left Atrial Appendage Occlusion with AtriClip in 155 Consecutive Patients - Single Center Study. Cor et Vasa. August 2017; 59(4): e376-e380.
34. van der Heijden CAJ, Weberndörfer V, Luermans JGLM, et al. Hybrid ablation of atrial fibrillation: A unilateral left-sided thoracoscopic approach. J Card Surg. Dec 2022; 37(12): 4630-4638. PMID 36349741
35. Branzoli S, Guarracini F, Marini M, et al. Heart Team for Left Atrial Appendage Occlusion: A Patient-Tailored Approach. J Clin Med. Dec 29 2021; 11(1). PMID 35011916
36. Cartledge R, Suwalski G, Witkowska A, et al. Standalone epicardial left atrial appendage exclusion for thromboembolism prevention in atrial fibrillation. Interact Cardiovasc Thorac Surg. Mar 31 2022; 34(4): 548-555. PMID 34871377
37. Franciulli M, De Martino G, Librera M, et al. Stand-Alone Thoracoscopic Left Atrial Appendage Closure in Nonvalvular Atrial Fibrillation Patients at High Bleeding Risk. Innovations (Phila). 2020; 15(6): 541-546. PMID 33048625
38. Joglar JA, Chung MK, Armbruster AL, 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. Circulation. Jan 02 2024; 149(1): e1-e156. PMID 38033089
39. Saw J, Holmes DR, Cavalcante JL, et al. SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure. Heart Rhythm. May 2023; 20(5): e1-e16. PMID 36990925
40. Wyler von Ballmoos MC, Hui DS, Mehaffey JH, et al. The Society of Thoracic Surgeons 2023 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation. Ann Thorac Surg. Jan 27 2024. PMID 38286206

Codes

Applicable Modifiers

N/A

Policy History