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Left-Atrial Appendage Closure or Clipping

Policy Number: MP-490

 

Latest Review Date: June 2019

Category: Medicine/Cardiology                                           

Policy Grade: B

Description of Procedure or Service:

Stroke prevention in patients with atrial fibrillation (AF) is an important goal of treatment. Treatment with anticoagulant medications is the most common approach to stroke prevention. Most embolic strokes originate from the left atrial appendage; therefore, occlusion of the left atrial appendage may offer a non-pharmacologic alternative to anticoagulant medications for this purpose. Multiple percutaneously-deployed devices are being investigated for left atrial appendage closure. One left atrial appendage device (the Watchman device) has approval from the U.S. Food and Drug Administration for stroke prevention in patients with AF.

Atrial Fibrillation and Stroke

AF is the most common type of irregular heartbeat, affecting at least 2.7 million people in the U. S. Stroke is the most serious complication of AF. The estimated incidence of stroke in nontreated patients with AF is 5% per year. 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 a main goal of AF treatment.

Stroke in AF occurs primarily as a result of thromboembolism from the left atrium. The lack of atrial contractions in atrial fibrillation leads to blood stasis in the left atrium, and this low flow state increases the risk for thrombosis. The area of the left atrium with the lowest blood flow in atrial fibrillation, and, therefore, the highest risk of thrombosis, is the left-atrial appendage (LAA). It has been estimated that 90% of left-atrial thrombi occur in the LAA.

Treatment

Pharmacologic

The main treatment for stroke prevention in AF is anticoagulation, which has proven efficacy. 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. Warfarin is the predominant agent in clinical use. A number of newer anticoagulant medications, including dabigatran, rivaroxaban, and apixaban, have recently received U.S. Food and Drug Administration (FDA) approval for stroke prevention in nonvalvular AF and have demonstrated non-inferiority to warfarin in clinical trials. While anticoagulation is effective for stroke prevention, there is an increased risk of bleeding. Also, warfarin requires frequent monitoring and adjustments, as well as lifestyle changes. Dabigatran does not require monitoring. However, unlike warfarin, the antithrombotic effects of dabigatran are not reversible with any currently available hemostatic drugs. Guidelines from the American College of Chest Physicians (2012) recommend the use of oral anticoagulation for patients with AF who are at high risk of stroke (i.e., CHADS2 score of 2 or greater), with more individualized choice of antithrombotic therapy in patients with lower stroke risk.

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

Letter

Clinical Characteristics

Points Awarded

C

Congestive heart failure (signs/symptoms of heart failure confirmed with objective evidence of cardiac dysfunction)

1

H

Hypertension (resting blood pressure >140/90 mmHg on at least 2 occasions or current antihypertensive pharmacologic treatment)

1

A

Age ≥75 y

2

D

Diabetes (fasting glucose >125 mg/dL or treatment with oral hypoglycemic agent and/or insulin)

1

S

Stroke or transient ischemic attack (includes any history of cerebral ischemia)

2

V

Vascular disease (prior myocardial infarction, peripheral arterial disease, or aortic plaque)

1

A

Age 65-74 y

1

Sc

Sex category of female (female sex confers higher risk)

1

Bleeding is the primary risk associated with systemic anticoagulation. Risk scores have been developed to estimate the risk of significant bleeding in patients treated with systemic anticoagulation. An example is the HAS-BLED score, which has validated to assess the annual risk of significant bleeding in patients with AF treated with warfarin. The score ranges from zero to nine, based on a number of clinical characteristics, including the presence of hypertension, renal and liver function, history of stroke, bleeding, labile international normalized ratios (INRs), age, and drug/alcohol use. Scores of three or greater are considered to be associated with high risk of bleeding, potentially signaling the need for closer monitoring of the patient for adverse risks, closer monitoring of INRs, or differential dose selections of oral anticoagulants or aspirin.

Surgery

Surgical removal, or exclusion, of the LAA is often performed in patients with atrial fibrillation who are undergoing open heart surgery for other reasons. Percutaneous LAA closure devices have been developed as a nonpharmacologic alternative to anticoagulation for stroke prevention in atrial fibrillation. The devices may prevent stroke by occluding the LAA, thus preventing thrombus formation.

Several versions of the devices have been developed. The PLAATO system (ev3 Endovascular) was the first device to be approved by the FDA for LAA occlusion. The device was discontinued in 2007 for commercial reasons, and intellectual property was sold to manufacturers of the Watchman system. The WATCHMAN® left atrial appendage system (Boston Scientific, Maple Grove, MN) is a self-expanding nickel titanium device. It has a polyester covering and fixation barbs for attachment to the endocardium. Implantation is performed percutaneously through a catheter delivery system, utilizing venous access and transseptal puncture to enter the left atrium. Transesophageal echocardiography and fluoroscopy are used to guide the procedure. Following implantation, patients are anticoagulated with warfarin or alternate agents for approximately one-two months. After this period, patients are maintained on antiplatelet agents (i.e., aspirin and/or clopidogrel) indefinitely.  The Amplatzer cardiac plug (St. Jude Medical, Minneapolis, MN), is FDA-approved for closure of atrial septal defects but not for LAA closure. A second-generation device, the Amplatzer Amulet, has been developed for the specific indication of LAAC, but currently does not have the FDA approval. The Amplatzer Amulet consists of a nitinol mesh disc to seal the ostium of the LAA and a nitinol mesh distal lobe, to be positioned within the LAA. The device is preloaded within a delivery sheath. The Percutaneous LAA Transcatheter Occlusion (PLATTO) device (eV3, Plymouth MN) has also been studied for this purpose but has not received FDA approval. The Occlutech® (Occlutech, Sweden) Left Atrial Appendage Occluder (has received a CE mark for coverage in Europe. The Cardioblate® closure device (Medtronic) is currently being tested in clinical studies.

The Lariat Loop Applicator is a suture delivery device approved by the FDA, intended to close a variety of surgical wounds. It is not specifically approved for LAAC. While the Watchman and other devices are implanted in the endocardium, the Lariat is a non-implant epicardial device.

Outcome Measures

The optimal study design for evaluating the efficacy of percutaneous LAAC for the prevention of stroke in AF is a randomized controlled trial that includes clinically relevant measures of health outcomes. The rate of ischemic stroke during follow-up is the primary outcome of interest, along with rates of systemic embolization, cardiac events, bleeding complications, and death. For the LAAC devices, the appropriate comparison group could be oral anticoagulation, no therapy (for patients who have prohibitive risk for oral anticoagulation), or open surgical repair.

Although the Watchman device and other LAAC devices would ideally represent an alternative to oral anticoagulation for the prevention of stroke in patients with AF, during the postimplantation period, the device may be associated with increased thrombogenicity and, therefore, anticoagulation is used during the periprocedural period. Most studies evaluating the Watchman device have included patients who are eligible for anticoagulation.

Policy:

Effective for Dates of Service on and after June 10, 2019:

The use of a device with U.S. Food and Drug Administration (FDA) approval for percutaneous left atrial appendage closure (e.g., the Watchman) may be considered medically necessary for the prevention of stroke in patients with atrial fibrillation when the following criteria are met:

  • There is an increased risk of stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc score and systemic anticoagulation therapy is recommended; and

  • The long-term risks of systemic anticoagulation outweigh the risks of the device implantation.

The use of a device with FDA approval for percutaneous left atrial appendage closure (e.g., the Watchman) for stroke prevention in patients who do not meet the above criteria is considered investigational.

The use of other percutaneous left atrial appendage closure devices, including but not limited to the Lariat and Amplatzer devices, for stroke prevention in patients with atrial fibrillation is considered investigational.

Effective for Dates of Service prior to June 10, 2019:

Left-atrial appendage closure devices performed via thoracotomy, percutaneously or with concomitant procedure are considered not medically necessary and investigational.

Epicardial clipping of the left atrial appendage is considered not medically necessary and investigational, including but not limited to, atrial fibrillation and all other indications.

Key Points:

The most recent update with literature review covers the period of through March 25, 2019.

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. RCTs 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.

The evidence on the efficacy of left atrial appendage (LAA) closure devices consists of numerous case series of various occlusion devices, two published randomized controlled trial (RCT) of the Watchman™ device, the PROTECT AF and PREVAIL trials, that compared LAA closure with warfarin anticoagulation. Evidence on each different device will be reviewed separately, because the devices are not similar in design, and each may have its own unique considerations.

WATCHMAN® Device

Clinical Context and Therapy Purpose

The purpose of the Watchman device in patients who have atrial fibrillation (AF) and are at increased risk for embolic stroke is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of the Watchman device improve net health outcomes compared with systemic anticoagulation treatment in patients with AF who are at increased risk for embolic stroke?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest are patients with AF. AF causes a low flow state in the left atrium which increases the risk of thromboembolism. Strokes in patients with AF occur primarily due to thromboembolism from the left atrium. Patients with AF who are not treated have a 5% estimated incidence of stroke.

Interventions

The therapy being considered is use of the Watchman percutaneous left atrial appendage (LAA) closure device. The device is made of nickel titanium and is implanted percutaneously through a catheter, into the left atrium. The Watchman comes in five sizes and self-expands to occlude the LAA. By occluding the LAA, thrombus formation is prevented, potentially preventing stroke. Following implantation of the device, the patient receives warfarin for one to two months. Once it is established that there is no peridevice leak or thrombus development, the patient is then placed on antiplatelet agents indefinitely.

Comparators

The current treatment for stroke prevention in patients with AF is systemic anticoagulation. While anticoagulants are effective in preventing stroke, the increased risk of bleeding is a potential harm. Warfarin, which is the most common anticoagulant in use, requires frequent monitoring and lifestyle changes. Other anticoagulants, found to be noninferior to warfarin, include dabigatran, rivaroxaban, and apixaban.

Outcomes

The general outcomes of interest are rates of ischemic or hemorrhagic stroke, cardiovascular or unexplained death, and systemic embolism, measured between 6 to 12 months of follow-up. Additional outcomes of interest include device- or procedure-related events that may occur within one week of the procedure. In particular, events requiring open cardiac surgery or major endovascular intervention (eg, pseudoaneurysm repair, arteriovenous fistula repair, or other major endovascular repair) should be noted.

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 effects, single-arm studies that capture longer periods of follow-up and/or larger populations were sought;

  • Studies with duplicative or overlapping populations were excluded.

Systematic Reviews

A TEC Assessment in 2014, evaluated the use of the Watchman device for patients who were eligible and ineligible for anticoagulation therapy and determined that it does not meet Technology Evaluation Criteria. The assessment determined that the device did not meet TEC criteria. The Assessment made the following conclusions about the use of LAA closure in patients without contraindications to anticoagulation:

“We identified two randomized controlled trials (RCTs) and one case series evaluating the Watchman™ device. The RCTs were noninferiority trials and compared LAAC with anticoagulation. The first trial showed a lower rate of a composite outcome (stroke, death, and embolism) in patients receiving LAAC [left atrial appendage closure] and met noninferiority criteria compared with anticoagulation, but FDA [Food and Drug Administration] review noted problems with patient selection, potential confounding with other treatments, and losses to follow-up. The second trial, which incorporated the first trial’s results as a discounted informative prior in a Bayesian analysis, showed similar rates of the same composite outcome but did not meet noninferiority criteria. The second trial met its second principal outcome noninferiority criteria in one of two analyses and a performance goal for short-term complication rate. When assessing the results of both trials, the relative performance of LAAC and anticoagulation is uncertain.”

A number of systematic reviews published after the TEC Assessment have combined the results of the available RCTs. Others have included RCTs and observational studies.

The most rigorous meta-analysis is a patient-level meta-analysis by Holmes et al (2015). This study reported results of a patient-level data from the industry-sponsored PROTECT AF and PREVAIL trials, described below, together with both studies’ continued access registries. The PROTECT AF and PREVAIL registries were designed to include patients with similar baseline characteristics as their respective RCTs. The meta-analysis included a total of 2406 patients, 1877 treated with the Watchman device and 382 treated with warfarin alone. Mean patient follow-up durations were 0.58 years and 3.7 years, respectively, for the PREVAIL continued access registry and the PROTECT AF continued access registry. In a meta-analysis of 1114 patients treated in the RCTs, compared with warfarin, LAA closure met the study’s noninferiority criteria for the primary composite efficacy end point of all-cause stroke, systemic embolization, and cardiovascular death (hazard ratio [HR], 0.79, 95% confidence interval [CI], 0.52 to 1.2; p=0.22). All-cause stroke rates did not differ significantly between groups (1.75 per 100 patient-years for LAA closure vs 1.87 per 100 patient-years for warfarin; HR=1.02; 95% CI, 0.62 to 1.7; p=0.94). However, LAA closure‒treated patients had higher rates of ischemic stroke (1.6 events/100 patient-years vs 0.9 events/100 patient-years; HR=1.95, p=0.05) when procedure-related strokes were included, but had lower rates of hemorrhagic stroke (0.15 events/100 patient-years vs 0.96 events/100 patient-years; HR=0.22; 95% CI, 0.08 to 0.61; p=0.004).

A second patient-level meta-analysis of the 2 RCTs, reported by Price (2015), evaluated bleeding outcomes. There were a total of 54 episodes of major bleeding, with the most common types being gastrointestinal (GI) bleed (31/54 [57%]) and hemorrhagic stroke (9/54 [17%]). On combined analysis, the rate of major bleeding episodes over the entire study period did not differ between groups. There were 3.5 events per 100 patient-years in the Watchman group compared with 3.6 events per 100 patient-years in the anticoagulation group, for a rate ratio (RR) of 0.96 (95% CI, 0.66 to 1.40; p=0.84). However, there was a reduction in bleeding risk for the Watchman group past the initial periprocedural period. For bleeding events occurring more than 7 days postprocedure, the event rates were 1.8 per 100 patient-years in the Watchman group compared with 3.6 per 100 patient-years in the anticoagulation group (RR=0.49; 95% CI, 0.32 to 0.75; p=0.01). For bleeding events occurring more than 6 months postprocedure (the time at which antiplatelet therapy is discontinued for patients receiving the Watchman device), the event rates were 1.0 per 100 patient-years in the Watchman group compared with 3.5 per 100 patient-years in the anticoagulation group (RR=0.28; 95% CI, 0.16 to 0.49; p<0.001).

Additional systematic reviews have used network meta-analyses to compare Watchman with novel oral anticoagulants and vitamin K antagonists (6 RCTs, n=59,627 subjects), and have compared percutaneous LAA occlusion (5 RCTs, N=1285 subject) with standard anticoagulant or antiplatelet therapy with device-based surgical or percutaneous LAA exclusion. In the network meta-analysis comparing vitamin K antagonists with novel oral anticoagulants and with the Watchman device, Bajaj et al (2016) report that all the treatment strategies had comparable ischemic stroke rates. However, the cluster analyses showed the novel oral anticoagulants ranked best in safety and efficacy, followed by vitamin K antagonists, and then the Watchman device. Interpretation of these results is limited by the small sample sizes and population heterogeneity in the RCTs comparing the Watchman with vitamin K antagonists. The network meta-analysis comparing LAAC with oral anticoagulants, antiplatelets, and placebo, reported a trend in stroke and mortality favoring LAAC, but the differences were not statistically significant. The authors noted that overall quality of the evidence was low.

Baman et al (2018) conducted a systematic review of LAA closure devices, including Watchman, Amplatzer cardiac plug, Amplatzer Amulet, and Lariat devices. The literature search, conducted through April 2017, identified 2 RCTs and 15 registry studies. No meta-analyses were conducted. The authors concluded that the Watchman may be noninferior to warfarin and that long-term efficacy outcomes are promising. For the remaining devices included in the review, the authors note that high-quality prospective studies comparing the devices to each other and with anticoagulants are needed.

Randomized Controlled Trials

Described below are two RCTs comparing the Watchman with oral anticoagulants and one RCT comparing the Watchman to the AMPLATZER cardiac plug.

PROTECT-AF

The first RCT published is the PROTECT-AF study, which was a randomized, unblinded trial that evaluated the non-inferiority of an LAA closure device compared with warfarin for stroke prevention in AF. The trial randomized 707 patients from 59 centers in the U.S. and Europe to the Watchman device or warfarin treatment in a 2:1 ratio. Mean follow-up was 18 +/- 10 months. The primary efficacy outcome was a composite end point of stroke (ischemic or hemorrhagic), cardiovascular or unexplained death, or systemic embolism. There was also a primary safety outcome, which was a composite end point of excessive bleeding (intracranial or gastrointestinal [GI] bleeding) and procedure-related complications (pericardial effusion, device embolization, procedure-related stroke).

The primary efficacy outcome occurred at a rate of 3.0 per 100 patient years in the LAA closure group compared with 4.9 per 100 patient years in the warfarin group (rate ratio [RR]=0.62; 95% credible interval [CrI], 0.35 to 1.25). Based on these outcomes, the probability of non-inferiority was greater than 99.9%. For the individual components of the primary outcome, cardiovascular/unexplained death and hemorrhagic stroke were higher in the warfarin group. In contrast, ischemic stroke was higher in the LAA closure group at 2.2 per 100 patient years compared with 1.6 per 100 patient years in the warfarin group (RR=1.34; 95% CI, 0.60 to 4.29).

The primary safety outcome occurred more commonly in the LAA closure group, at a rate of 7.4 per 100 patient years compared with 4.4 per 100 patient years in the warfarin group (RR=1.69; 95% CrI, 1.01 to 3.19). The excess in adverse event rates for the LAA closure group were primarily the result of early adverse events associated with placement of the device. The most frequent type of complication related to LAA closure device placement was pericardial effusion requiring intervention, which occurred in 4.8% of patients (22/463).

Longer term follow-up from the PROTECT AF study was reported by Reddy et al in 2013. At a mean follow-up of 2.3 years, the results were similar to the initial report. The relative risk for the composite primary outcome in the Watchman group compared with anticoagulation was 0.71, and this met non-inferiority criteria with a confidence of greater than 99%. Complications were more common in the Watchman group, with an estimated rate of 5.6%/year in the Watchman group compared with 3.6%/year in the warfarin group.

Outcomes through four years of follow-up were reported by Reddy et al in 2014. Mean follow-up was 3.9 years in the LAA closure group and 3.7 years in the warfarin group. In the LAA closure group, warfarin was discontinued in 345 of 370 patients (93.2%) by the 12 month follow-up evaluation. During the follow-up period, the relative risk for the composite primary outcome in the Watchman group compared with anticoagulation was 0.60 (8.4% in the device group vs 13.9% in the anticoagulation group; 95% CrI, 0.41 to 1.05), which met the noninferiority criteria with a confidence of greater than 99.9%. Fewer hemorrhagic strokes occurred in the Watchman group (0.6% vs 4.0%; RR=0.15; 95% CrI, 0.03 to 0.49), and fewer cardiovascular events occurred in the Watchman group (3.7% vs 0.95%; RR=0.40; 95% CrI, 0.23 to 0.82). Rates of ischemic stroke did not differ significantly between groups, but Watchman group patients had lower all-cause mortality than anticoagulation group patients (12.3% vs 18.0%; HR=0.66; 95% CI, 0.45 to 0.98; p=0.04).

Alli et al reported quality-of-life parameters, as measured by change in scores on the Short-Form 12 Health Survey from baseline to 12 months of follow up, for a subset of 547 subjects in the PROTECT AF study. For the subset of PROTECT AF subjects included in the present analysis, at baseline, control group subjects had a higher mean CHADS2 score (2.4 vs 2.2; p=0.0517) and were more likely to have a history of coronary artery disease (49.5% vs 39.6%; p=0.0275). For subjects in the Watchman group, the total physical score improved in 34.9% and was unchanged in 29.9%; for those in the warfarin group, the total physical score improved in 24.7% and was unchanged in 31.7% (p=0.01).

Five-year follow-up results, published by Reddy et al (2017), indicated that the LAAC group had significantly lower rates of the composite efficacy endpoint (stroke, systemic embolism, cardiovascular death) compared with the warfarin-only group (p=0.04)

PREVAIL

A second RCT, the PREVAIL trial, was conducted after the 2009 FDA decision on the Watchman device to address some of the limitations of the PROTECT AF study, including its inclusion of patients with low stroke risk (CHADS2 scores of 1), high rates of adjunctive antiplatelet therapy use in both groups, and generally poor compliance with warfarin therapy in the control group. Results from the PREVAIL trial were published by Holmes et al in 2014. In the PREVAIL trial, 461 subjects enrolled at 41 sites were randomized in a 2:1 fashion to either the Watchman™ device or control, which consisted of either initiation or continuation of warfarin therapy with a target international normalized ratio (INR) of 2.0-3.0. Subjects had nonvalvular AF and required treatment for prevention of thromboembolism based on a CHADS2 score of two or higher (or one or higher with other indications for warfarin therapy based on American College of Cardiology/American Heart Association/European Society of Cardiology guidelines) and were eligible for warfarin therapy. In the device group, warfarin and low-dose aspirin were continued until 45 days postprocedure; if a follow-up echocardiogram at 45 days showed occlusion of the LAA, warfarin therapy could be discontinued. Subjects who discontinued warfarin were treated with aspirin and clopidogrel for six months post-device implantation and with 325 mg aspirin indefinitely after that.

Three non-inferiority primary efficacy end points were specified: 1) occurrence of ischemic or hemorrhagic stroke, cardiovascular or unexplained death, and systemic embolism (18 month rates); 2) occurrence of late ischemic stroke and systemic embolization (beyond seven days post-randomization, 18-month rates); and 3) occurrence of all-cause death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring open cardiac surgery or major endovascular intervention (e.g., pseudoaneurysm repair, arteriovenous fistula repair, or other major endovascular repair) occurring within seven days of the procedure or by hospital discharge, whichever was later. The 18-month event rates were determined using Bayesian statistical methods to integrate data from the PROTECT-AF study.  All patients had a minimum follow-up of six months.  For randomized subjects, the mean follow-up was 11.8 months and the median follow-up was 12.0 months (range 0.03-25.9 months).

The first primary end point, the 18-month modeled RR between the device and control groups was 1.07 (95% Crl, 0.57 to 1.89). Because the upper bound of the 95% credible interval was above the preset non-inferiority margin of 1.75, the non-inferiority criteria were not met. For the second primary end point of late ischemic stroke and systemic embolization, the 18-month RR between the device and control groups was 1.6 (95% Crl, 0.5 to 4.2), with an upper bound of the 95% credible interval above the preset non-inferiority margin of 2.0. The rate difference between the device and control groups was 0.0053 (95% Crl, -0.0190 to 0.0273). The upper bound of the 95% credible interval was lower than the non-inferiority margin of 0.0275, so the non-inferiority criterion was met for the rate difference. For the third primary end point, major safety issues, the non-inferiority criterion was met.

Five-year follow-up results, published by Reddy et al (2017), indicated that the Watchman device was noninferior to warfarin alone in the composite efficacy end point (stroke, systemic embolism, cardiovascular death) (p=0.47).

In addition to providing 5 year final results for the individual trials, Reddy et al (2017) conducted a meta-analysis of the 5-year outcomes using data from both trials. Meta-analytic results are summarized in Table 2, showing that the Watchman device is noninferior to warfarin alone in stroke prevention among patients with nonvalvular AF. In addition, patients treated with the Watchman device experienced significantly lower bleeding and mortality compared with patients receiving Warfarin.

Table 2. Five-Year Meta-Analytics Results for the PROTECT AF and PREVAIL AF Trials

Outcomes

Watchman, n (Rate per 100 PY)

Warfarin Alone, n (Rate per 100 PY)

HR (95% CI)

p

Composite stroke/SE/CV death

79 (2.8%)

50 (3.4%)

0.8 (0.6 to 1.2)

0.3

All stroke or SE

49 (1.7%)

27 (1.8%)

1.0 (0.6 to 1.5)

0.9

CV/unexplained death

39 (1.3%)

33 (2.2%)

0.6 (0.4 to 0.9)

0.03

All cause death

106 (3.0%)

73 (4.9%)

0.7 (0.5 to 1.0)

0.03

Major bleeding, all

85 (3.1%)

50 (3.5%)

0.9 (0.6 to 1.3)

0.6

Major bleeding, non-LAAC-related

48 (1.7%)

51 (3.6%)

0.5 (0.3 to 0.7)

<0.001

Adapted from Reddy et al (2017). CI: confidence interval; CV: cardiovascular; HR: hazard ratio; LAAC: left atrial appendage closure; PY: patient-years;

SE: systemic embolism.

Chun et al (2013) compared the Watchman device with the Amplatzer cardiac plug among patients who had nonvalvular AF, were at high-risk for stroke, and had a contraindication to or were unwilling to take oral anticoagulants. Eighty patients were randomized to LAA occlusion with the Watchman or the Amplatzer device. After device implantation, either preexisting oral anticoagulation therapy or dual-platelet inhibition with aspirin and clopidogrel was continued for six weeks. There were no statistically significant differences in procedure time, fluoroscopy time, or major safety events between the two groups. At a median follow-up of 364 days, there were no cases of stroke, transient ischemic attack, or other bleeding complications.

Nonrandomized Studies

Numerous case series and nonrandomized studies have been published. Several are notable in that they were conducted in patients not eligible for anticoagulation, a population not included in PROTECT AF and PREVAIL. Reddy et al conducted a multicenter, prospective, nonrandomized trial to evaluate the safety and efficacy of LAAC with the Watchman device in patients with nonvalvular AF with a CHADS2 score 1 or higher who were considered ineligible for warfarin. Postimplantation, patients received 6 months of clopidogrel or ticlopidine and lifelong aspirin therapy. Thirteen (8.7%) patients had a procedure- or device-related serious adverse event, most commonly pericardial effusion (3 patients). Over a mean 14.4 months of follow-up, all-cause stroke or systemic embolism occurred in 4 patients.

The EWOLUTION Watchman registry is intended to evaluate procedural success, long-term outcomes, and adverse events in real-world settings. This registry compiles data from patients receiving the Watchman device at 47 centers in 13 countries. A publication from the EWOLUTION registry in 2016 reported on 30-day outcomes of device implantation in 1021 patients. The overall population had a risk of bleeding that was substantially higher than that for patients in the RCTs. Over 62% of patients included in the registry were deemed ineligible for anticoagulation by their physicians. Approximately one-third of patients had a history of major bleeding, and 40% had HAS-BLED scores of 3 or greater, indicating moderate-to-high risk of bleeding. Procedural success was achieved in 98.5% of patients, and 99.3% of implants demonstrated no blood flow or minimal residual blood flow postprocedure. Serious adverse events due to the device or procedure occurred at an overall rate of 2.8% (95% CI, 1.9% to 4.0%) at 7 days and 3.6% (95% CI, 2.5% to 4.9%) at 30 days. The most common serious adverse event was major bleeding.

Dukkipati et al (2018) studied the incidence, predictors, and clinical outcomes of device-related thrombus (DRT) among the following patients receiving the Watchman in the following trials and registries: PROTECT-AF, PREVAIL, Continued Access to PROTECT-AF registry, and Continued Access to PREVAIL registry. Surveillance transesophageal electrocardiograms were conducted in all patients at 45 days and 12 months. Patients in the RCTs also received the electrocardiograms at six months. A total of 1739 patients were followed for a total of 7159 patient-years. Mean age of the population was 74 years and 34% were women. DRT was detected in 65 (3.7%) of the patients. Stroke or systemic embolism rates were 7.5 and 1.8 per 100 patient-years for patients with and without DRT, respectively. A multivariable modeling analysis found the following predictors of DRT: history of transient ischemic attack or stroke, permanent AF, vascular disease, LAA diameter, and left ventricular ejection fraction.

Jazayeri et al (2018) evaluated the safety profiles of the Watchman and the Lariat devices, using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016. MAUDE consists of mandatory reports from manufacturers and voluntary reports from healthcare professionals and patients. Outcomes assessed included: a composite of stroke/TIA, pericardiocentesis, cardiac surgery, and death; DRT; cardiac surgery; and myocardial infarction. A total of 5849 Watchman devices were implanted, with 472 events reported during the study period. The most common events in patients receiving the Watchman, were device malfunction (97 [1.7%]), pericardial effusion (84 [1.4%]), need for pericardiocentesis (57 [0.97%]), and intracardiac thrombus (47 [0.84%]). Twenty deaths were reported in the Watchman group, with one likely related to DRT. Compared to the Lariat device, the composite outcome occurred significantly more in the group receiving the Watchman than within the group receiving the Lariat, 1.9% vs 1.1%, p=0.001). Analysis results for the Lariat device will be discussed in the next section, "Other Closure Devices".

Section Summary: Watchman Device

The most relevant evidence on the use of the Watchman device for LAAC in patients eligible for anticoagulation derives from two industry-sponsored RCTs comparing Watchman and systemic anticoagulants and a patient-level meta-analysis of those studies. After five years of follow-up, meta-analytic results showed that the ischemic stroke risk beyond seven days did not differ between groups and that the hemorrhagic stroke risk remained significantly lower in the LAAC group. The results showed that the Watchman device is noninferior to warfarin alone in stroke prevention among patients with nonvalvular AF. Also, patients treated with the Watchman device experienced significantly lower bleeding and mortality. A large study of patients receiving the Watchman device (combining patients from the two RCTs and two registries) reported that patients who developed DRT were four times more likely to experience a stroke or systemic embolism. The authors suggest a surveillance strategy for patients at high-risk of DRT following Watchman implantation.

Other Closure Devices

Clinical Context and Therapy Purpose

The purpose of other LAA closure devices in patients who have AF and are at increased risk for embolic stroke is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does the use of other LAA closure devices improve net health outcomes compared with systemic anticoagulation treatment in patients with AF who are at increased risk for embolic stroke?

The following PICOTS were used to select literature to inform this review.

Patients

The relevant population of interest is patients with AF. AF causes a low flow state in the left atrium which increases the risk of thromboembolism. Strokes in patients with AF occur primarily due to thromboembolism from the left atrium. Patients with AF who are not treated have a 5% estimated incidence of stroke.

Interventions

The interventions of interest are other LAA occlusion devices. By occluding the LAA, thrombus formation is prevented, potentially preventing stroke. Other devices currently being evaluated for the use of LAA occlusion include:

  • The Lariat Loop Applicator is a suture delivery device approved by the FDA to facilitate suture placement and knot tying for use in surgical applications where soft tissues are being approximated or ligated with a pretiedpolyester suture. The approved use does not specify LAA occlusion. While the Watchman and other devices are implanted in the endocardium, the Lariat is a non-implant epicardial device. The Lariat is contraindicated in patients with active pericarditis; prior sternotomy or other mediastinal surgery or known pericardial adhesions; appendage width >45 mm; superiorly oriented appendage lying near or behind the pulmonary arterial trunk; or appendage thrombus.

  • The Amplatzer Amulet device comes in eight sizes to accommodate various patient anatomies. The mechanism of action is similar to the Watchman. Following implantation of the Amulet, patients are placed on antiplatelet agents and do not need warfarin. There is an ongoing trial comparing the Amplatzer Amulet with the Watchman (NCT03399851).

Comparators

The current treatment for stroke prevention in patients with AF is systemic anticoagulation. While anticoagulants are effective in preventing stroke, the increased risk of bleeding is a potential harm. Warfarin, which is the most common anticoagulant in use, requires frequent monitoring and lifestyle changes. Other anticoagulants, found to be noninferior to warfarin include dabigatran, rivaroxaban, and apixaban.

Outcomes

The general outcomes of interest are rates of ischemic or hemorrhagic stroke, cardiovascular or unexplained death, and systemic embolism, measured between 6 to 12 months of follow-up. Additional outcomes of interest include device- or procedure-related events that may occur within one week of the procedure, in particular, events requiring open cardiac surgery or major endovascular intervention (eg, pseudoaneurysm repair, arteriovenous fistula repair, or other major endovascular repair).

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 effects, single-arm studies that capture longer periods of follow-up and/or larger populations were sought;

  • Studies with duplicative or overlapping populations were excluded.

Lariat® Device

Systematic Review

A systematic review of published studies on the Lariat device was published in 2016. No RCTs were identified. Five case series were selected, with a total of 309 patients (range, 4-154 patients) treated. The combined estimate of procedural success was 90.3%. One (0.3%) death was reported and 7 (2.3%) patients required urgent cardiac surgery. The MAUDE database was searched for adverse events, and found 35 unique reports. Among the 35 reported complications, there were 5 deaths and 23 cases of emergency cardiac surgery.

Case Series

Individual case series published since the systematic review, include a large 2016 case series of 712 consecutive patients from 18 U.S. hospitals. This series reported a procedural (suture deployment) success rate of 95% and complete closure in 98%. The high success rate was attributed to the appropriate selection of patients for the procedure, which was determined by a screening computed tomography scan showing if the LAA anatomy was suitable for LARIAT deployment. There was 1 death and emergent cardiac surgery was required in 1.4%. Cardiac perforations (overall and those needing surgery) and number of patients needing blood transfusions decreased when providers altered the procedure from using large bore needles to micropuncture needles. Other individual case series are smaller, reporting success rates and complication rates in the same range.

Litwinowicz et al (2018) presented a case series of 139 patients from a single-center undergoing LAA closure with the Lariat device, with a longer follow-up than the other case series. After a follow-up of 5-years (428 patient-years), the thromboembolism rate was 0.8%, with a calculated bleeding risk reduction of 78%. The overall mortality rate was 1.6%.

Non-randomized Comparative Study

As described above in the Watchman section, Jazayeri et al (2018) evaluated the safety profiles of the Watchman and the Lariat devices, using the FDA's MAUDE database from 2009 to 2016. A total of 4889 Lariat devices were implanted, with 136 events reported during the study period. The most common events in the Lariat group were pericardial effusion (46 [0.94%]), need for cardiac surgery (38 [0.78%]), and pericardiocentesis (23 [0.47%]). Ten deaths were reported in the Lariat group, with six involving tightening of the suture around the LAA. Compared to the Watchman device, the composite outcome occurred significantly more in the group receiving the Watchman than in the group receiving the Lariat, 1.9% vs 1.1%, p=0.001.

Litwinowicz et al (2019) compared outcomes of patients undergoing LAA closure with the Lariat device (n=57) with patients receiving either warfarin or clopidogrel (n=31). Age, sex, and comorbidities were similar between the two groups. Treatment prior to the study differed significantly. The Lariat group received warfarin (93%), aspirin (4%), aspirin plus clopidogrel (2%) and no anticoagulation (1%). The control group received warfarin (87%) or clopidogrel (13%). However, there was no significant difference in CHA2DS2-VAS scores between the groups at baseline. Average follow-up in the Lariat group was 59 months and average follow-up in the control group was 60 months. There were no thromboembolic events in the Lariat group, while 9.6% of the control group experienced thromboembolic events (p=0.02). The bleeding risk reduction in the Lariat group was estimated at 53%.

Section Summary: Lariat Device

There are no RCTs of the Lariat device for LAAC. There was one non-randomized study comparing patients undergoing LAA closure with the Lariat device with patients receiving either anticoagulant or antiplatelet therapy. Results showed significantly fewer thromboembolic events in the group undergoing LAA closure with the Lariat device compared with the group receiving medication alone. The remaining evidence consisted of case series. The evidence is insufficient to draw conclusions about treatment efficacy.

Amplatzer® Cardiac Plug Device and Amplatzer Amulet Device

Amplatzer Cardiac Plug (first generation)

The available evidence on use of the Amplatzer® device for left atrial occlusion consists of a number of case series. The largest series identified was by Nietlispach et al, which included 152 patients from a single institution in Europe. Short-term complications occurred in 9.8% (15/152). Longer-term adverse outcomes occurred in 7% of patients, including two strokes, one peripheral embolization, and four episodes of major bleeding. Device embolization occurred in 4.6% (7/152) of patients.

Other reports of patients treated with the Amplatzer® device include a series of 90 patients from Belgium (2013), 86 patients from Portugal (2012), 37 patients from Italy, 35 patients from Spain (2013), 21 patients from Poland (2012), and 20 patients from China (2012). All series reported high procedural success rates, as well as various complications such as vascular complications, air embolism, esophageal injury, cardiac tamponade, and device embolization.

Several other case series have reported the use of the Amplatzer device in patients with a contraindication to oral anticoagulation therapy. The largest study, by Santoro et al (2016), reported outcomes, up to four years postprocedure, for 134 patients with nonvalvular AF and a long-term contraindication to oral anticoagulation treated with the Amplatzer device. Patients had a median CHA2DS2-VASc score of four and were generally considered at high risk for bleeding complications. Procedural success occurred in 93.3%, and three major procedure-related complications (two cases of cardiac tamponade, one case of pericardial effusion requiring drainage or surgery) occurred. Over a mean follow-up of 680 days, observed annual rates of ischemic strokes and any thromboembolic events were 0.8% and 2.5%, respectively.

Other case series have been published in this population, ranging from 37 to 100 patients. They also reported high success rates and low procedural complications.

Amplatzer Amulet (second generation)

A second generation device, the Amplatzer Amulet was developed to potentially lower device embolization rates, simplify the technical implantation procedure, and lower severe complication rates. The Amulet first became available in Europe in January 2013. Below are descriptions of studies comparing the amulet with the first generation cardiac plug. There is currently an ongoing trial comparing the Amplatzer Amulet with the Watchman (NCT03399851).

Case Series

Landmesser et al (2017) presented periprocedural (within 7 days of procedure) and early clinical outcomes (1 to 3 months postprocedure) from a multicenter registry of 1088 patients receiving the Amplatzer Amulet between June 2015 and September 2016. Technical success was defined as implantation of the device in the correct position, which was reported for 1078 (99%) of the patients. A composite of ischemic stroke, systemic embolism, and cardiovascular death occurred in 7 (0.6%) patients during the periprocedural period and in 15 (1.4%) patients between 7 days postprocedure and 3 months follow-up.

Landmesser et al (2018) provided updated analyses on 950 patients from the registry series described above who had 1-year follow-up data. Oral anticoagulants were used by 6% of the patients at 3, 6, and 12 months postprocedure. There were 29 ischemic strokes (27 patients), 9 patients experiencing a transient ischemic attack, and no systemic embolisms reported. The annualized bleeding rate was 10.3% per year, with 103 events in 87 patients, majority occurring within the first 7 days postprocedure. The DRT rate was 1.7% per year, with 18 events in 17 patients. A total of 88 patients died within the first year postprocedure, 53 were cardiovascular-related and 35 noncardiovascular. Two of the cardiovascular-related deaths were attributed to the device.

Non-randomized Comparative Studies

Gloekler et al (2015) reviewed records from 2 university hospitals' occlusion registries and conducted a retrospective analysis comparing the last 50 consecutive patients receiving the cardiac plug with the first 50 consecutive patients receiving the amulet. Follow-up examinations were performed between four to six months post-procedure. No significant differences between the two devices were detected in mortality, neurologic events, late pericardial effusions, major bleeding, device leaks, or device thrombi. Interpretation of these results is limited by the small sample size and short follow-up period.

Al-Kassou et al (2017) presented periprocedural and 2 to 3 month follow-up data for patients undergoing LAA occlusion with the Amplatzer cardiac plug and the Amplatzer Amulet. Periprocedural data was available for 99 patients receiving the cardiac plug and for 97 patients receiving the Amulet. Use of the Amulet was associated with significantly lower fluoroscopy time, lower radiation dose, and reduced amount of contrast dye. Occurrence of adverse events during the periprocedural period were comparable. Transesophageal echocardiographic follow-up data at 2 to 3 months was available for 81 patients receiving the cardiac plug and for 82 patients receiving the Amulet. None of the patients experienced DRT during this follow-up. Minor leaks were detected in 12 (15%) patients receiving the cardiac plug and in 4 (5%) patients receiving the Amulet (p=0.03).

Section Summary: Amplatzer Cardiac Plug Device and Amplatzer Amulet

There are no RCTs of the Amplatzer device for LAAC. There are two non-randomized studies comparing the first generation Amplatzer cardiac plug with the second generation Amplatzer Amulet, one of which reported procedural advantages of the Amulet over the cardiac plug. Both nonrandomized comparator studies reported no difference in clinical outcomes at first follow-up, two to six months. The remaining evidence consists of case series. The non-randomized comparator studies and the case series are insufficient to draw conclusions about treatment efficacy. There is an ongoing trial comparing the Amplatzer Amulet with the Watchman (NCT03399851).

Summary

For individuals who have AF who are at increased risk for embolic stroke who receive the Watchman percutaneous LAAC device, the evidence includes two RCTs and meta-analyses of these trials. The relevant outcomes are overall survival, morbid events, and treatment-related morbidity. The most relevant evidence comes from two industry-sponsored RCTs that compared the Watchman device with anticoagulation alone. One trial reported noninferiority on a composite outcome of stroke, cardiovascular/unexplained death, or systemic embolism after two years of follow-up, with continued benefits with the Watchman device after four years of follow-up. The second trial did not demonstrate noninferiority for the same composite outcome but did demonstrate noninferiority of the Watchman device to warfarin for late ischemic stroke and systemic embolization. Patient-level meta-analyses at five-year follow-up for the two trials reported that the Watchman device is noninferior to warfarin on the composite outcome of stroke, systemic embolism, and cardiovascular death. Also, the Watchman was associated with lower rates in major bleeding, particularly hemorrhagic stroke, and mortality over the long-term. The evidence also indicates that the Watchman device is efficacious in preventing stroke in the subset of patients with AF who are at increased risk for embolic stroke. Among patients in which the long-term risk of systemic anticoagulation exceeds the procedural risk of device implantation, the net health outcome will be improved. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have AF who are at increased risk for embolic stroke who receive a percutaneous LAAC device other than the Watchman device (e.g., the Lariat, Amplatzer), the evidence includes several nonrandomized comparator studies and uncontrolled case series. The relevant outcomes are overall survival, morbid events, and treatment-related morbidity. One nonrandomized study which compared outcomes among patients undergoing LAAC with the Lariat device with patients receiving anticoagulant or antiplatelet therapy, reported fewer thromboembolic events in the group receiving the Lariat device. Two nonrandomized studies compared the Amplatzer cardiac plug with the Amplatzer amulet. While the amulet may be technically easier to implant, clinical outcomes were similar between the two groups. The remaining evidence consists of case series of these devices which report high procedural success but also numerous complications. In addition, these devices do not have the FDA approval for LAAC. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

American Heart Association

The American Heart Association, in collaboration with the American College of Cardiology and the Hearth Rhythm Society (2019) published an update of their guideline for the management of patients with atrial fibrillation. A new recommendation in the guideline states: "Percutaneous LAA occlusion may be considered in patients with AF at increased risk of stroke who have contraindications to long-term anticoagulation." The class of recommendation is IIb and the level of evidence is B-NR (moderate quality of evidence, non-randomized). No other LAA closure devices are mentioned in the guideline.

Guideline Comparison

Andrade et al (2017) provided the following summary (see Table 3) comparing guidelines by American, Canadian, and European societies on left atrial appendage exclusion and closure for the management of atrial fibrillation.

Table 3. Comparison of American, Canadian, and European Guidelines on LAA Exclusion/Closure

Procedure

AHA/ACC/HRS

CCS

ESC

Surgical LAA closure (excision or obliteration of LAA)

May be considered in patients undergoing cardiac surgery (IIb)

Should be considered as part of surgical ablation of AF associated with mitral, aortic valve, or coronary artery bypass surgery

• May be considered in patients undergoing cardiac surgery (IIb)

• More data needed to confirm safety and efficacy of thoracoscopic exclusion

Percutaneous LAA exclusion

No recommendation

Not be used, except in research or in systematically documented use protocols in patients at high risk of stroke (CHADS2 ≥2) and antithrombotic therapy precluded

May be considered in patients with contraindications for long term anticoagulant treatment (IIb)

Adapted from Andrade et al (2017).

ACC: American College of Cardiology; AF: atrial fibrillation; AHA: American Heart Association; CCS: Canadian Cardiovascular Society; CHADS2: Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack; ESC: European Society of Cardiology; HRS: Heart Rhythm Society; LAA: left atrial appendage.

American College of Cardiology, Heart Rhythm Society, et al

In 2015, the American College of Cardiology (ACC), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography and Interventions published an overview of the integration of percutaneous LAA closure devices into the clinical practice of patients with AF. The overview was organized around questions related to the sites of care delivery for LAA closure devices, training for proceduralists, necessary follow-up data collection, identification of appropriate patient cohorts, and reimbursement. The statement provides general guidelines for facility and operator requirements, including the presence of a multidisciplinary heart team, for centers performing percutaneous LAA closures. The statement does not provide specific recommendations about the indications and patient populations appropriate for percutaneous LAA closure.

U.S. Preventive Services Task Force Recommendations

LAA closure devices are not preventive services and are therefore not included in the U.S. Preventive Task Force Recommendations for preventive services.

Key Words:

Left Atrial Appendage Closure Device, WATCHMAN®, LARIAT®, AMPLATZER®, PLATTO, LAA

Approved by Governing Bodies:

In 2002, the PLAATO system (ev3 Endovascular) was the first device to be approved by the U.S. Food and Drug Administration (FDA) for LAA occlusion. The device was discontinued in 2007 for commercial reasons and intellectual property was sold to manufacturers of the Watchman system.

In 2015, the Watchman™ Left Atrial Appendage Closure Technology (Boston Scientific) was approved by the FDA through the premarket approval process by the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients with Atrial Fibrillation randomized controlled trial. This device is indicated to reduce the risk of thromboembolism from the LAA in patients with nonvalvular AF who:

  • Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for anticoagulation therapy;

  • Are deemed by their physicians to be suitable for warfarin; and

  • Have an appropriate rationale to seek a nonpharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared with warfarin.

Other devices are being evaluated for LAA occlusion, but are not approved in the U.S. for percutaneous closure of the LAA. The Lariat® Loop Applicator device (SentreHEART, Inc, Redwood City, CA) is a suture delivery system that received 510(k) marketing clearance from FDA in 2006. The intended use is to facilitate suture placement and knot tying in surgical applications where soft tissues are being approximated or ligated with a pre-tied polyester suture. The Amplatzer Amulet® device (St. Jude Medical, Plymouth, MN) and WaveCrest® (Coherex Medical) have CE approval in Europe for left atrial appendage closure, but are not currently approved in the U.S. for this indication.

Benefit Application:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity

>Current Coding:

CPT Codes:   

33340

Percutaneous transcatheter closure of the left atrial appendage with endocardial implant, including fluoroscopy, transseptal puncture, catheter placement(s), left atrial angiography, left atrial appendage angiography, when performed, and radiological supervision and interpretation. (Effective 01/01/17)

Previous Coding:

CPT Codes:

0281T

Percutaneous transcatheter closure of the left atrial appendage with implant, including fluoroscopy, transseptal (Deleted 12/31/16)

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  40. Landmesser, UU, Schmidt, BB, Nielsen-Kudsk, JJ, Lam, SS, Park, JJ, Tarantini, GG, Cruz-Gonzalez, II, Geist, VV, Della Bella, PP, Colombo, AA, Zeus, TT, Omran, HH, Piorkowski, CC, Lund, JJ, Tondo, CC, Hildick-Smith, DD. Left atrial appendage occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study. EuroIntervention, 2017 Jun 27;13(7).

  41. Landmesser, UU, Tondo, CC, Camm, JJ, Diener, HH, Paul, VV, Schmidt, BB, Settergren, MM, Teiger, EE, Nielsen-Kudsk, JJ, Hildick-Smith, DD. Left atrial appendage occlusion with the AMPLATZER Amulet device: one-year follow-up from the prospective global Amulet observational registry. EuroIntervention, 2018 May 29;14(5).

  42. Li X, Wen SN, Li SN, et al. Over 1-year efficacy and safety of left atrial appendage occlusion versus novel oral anticoagulants for stroke prevention in atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials and observational studies. Heart Rhythm. Dec 24 2015.

  43. Lip GY, Lane DA. Stroke prevention in atrial fibrillation: a systematic review. JAMA. May 19 2015; 313(19):1950-1962.

  44. Litwinowicz, RR, Bartus, MM, Burysz, et al. Long term outcomes after left atrial appendage closure with the LARIAT device-Stroke risk reduction over five years follow-up. PLoS ONE, 2018 Dec 20;13(12).

  45. Litwinowicz, RR, Bartus, MM, Kapelak, et al. Reduction in risk of stroke and bleeding after left atrial appendage closure with LARIAT device in patients with increased risk of stroke and bleeding: Long term results. Catheter Cardiovasc Interv, 2019 Mar 19.

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  47. Masoudi FA, Calkins H, Kavinsky CJ, et al. 2015 ACC/HRS/SCAI Left Atrial Appendage Occlusion Device Societal Overview. J Am Coll Cardiol. Sep 29 2015; 66(13):1497-1513.

  48. Massumi A, Chelu MG, Nazeri A et al. Initial experience with a novel percutaneous left atrial appendage exclusion device in patients with atrial fibrillation, increased stroke risk, and contraindications to anticoagulation. Am J Cardiol 2013 Mar 15; 111(6):869-73

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Policy History:

Medical Policy Group, December 2011 (3)

Medical Policy Administration Committee, December 2011

Available for comment December 14, 2011 through January 27, 2012

Medical Policy Group, March 2012 (3): 2012 Updates to Description, Key Points & References

Medical Policy Panel, March 2013

Medical Policy Group, June 2013 (4): 2013 Updates to Description, Key Points, Key Words & References; no change in policy statement

Medical Policy Panel, July 2014

Medical Policy Panel, July 2014 (4): Updated Description, updated Key Points to include Practice Guidelines, updated Approved Governing Bodies and References.  There were no changes to the policy at this time.

Medical Policy Group, May 2015 (4):  Update to Approved Governing Bodies

Medical Policy Panel, October 2015

Medical Policy Group, December 2015 (4): Updates to Description, Key Points, Approved Governing Bodies, and References. No change to policy statement.

Medical Policy Panel, May 2016

Medical Policy Group, June 2016 (4): Updates to Key Points and References.  No change to policy statement.

Medical Policy Group, December 2016: 2017 Annual Coding Update. Created Previous Coding section and moved deleted code 0281T to this section. Added new CPT code 33340 to Current Coding.

Medical Policy Panel, May 2017

Medical Policy Group, May 2017 (4): Updates to Description, Key Points, Key Words and References.  No change to policy statement.

Medical Policy Panel, 2018

Medical Policy Group, May 2018 (4): Updates to Description, Key Points, Approved by Governing Bodies, and References.  No change to policy statement.

Medical Policy Group June 2018: Clarified policy statement to include other devices and routes.

Medical Policy Administration Committee, June 2018

Available for comment June 14 through July 28, 2018

Medical Policy Panel, May 2019

Medical Policy Group, June 2019 (4): Updates to Description, Policy, Key Points, and References.  Updated policy statements to allow coverage for FDA approved LAAs with criteria.

Medical Policy Administrative Committee: June 2019

Available for Comment: June 11, 2019 through July 29, 2019


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.