J Interv Card Electrophysiol (2015) 43:79–89 DOI 10.1007/s10840-015-9988-1


Left atrial appendage occlusion for prevention of stroke in nonvalvular atrial fibrillation: a meta-analysis Weeranun D. Bode & Nikhil Patel & Anil K. Gehi

Received: 21 September 2014 / Accepted: 9 February 2015 / Published online: 25 February 2015 # Springer Science+Business Media New York 2015

Abstract Purpose When anticoagulation for stroke prevention is contraindicated, left atrial appendage occlusion (LAAO) may be performed. Studies of LAAO have been limited by their small size, disparate patient populations, and lack of control group. Our purpose was to perform a meta-analysis of the safety and efficacy of LAAO in comparison with standard therapy for stroke prevention in nonvalvular AF. Methods Due to the lack of a control group in studies of LAAO, data on stroke prevention from multiple large outcomes studies were used to produce a hypothetical control group based on clinical variables in the individual studies. Results were stratified according to LAAO device type. Results We identified 16 studies with a total of 1759 patients receiving LAAO. Summary estimates demonstrate LAAO reduced risk of stroke in comparison with no therapy or aspirin therapy [relative risk (RR), 0.34; 95 % CI, 0.25–0.46] and in comparison with warfarin therapy (RR, 0.65; 95 % CI, 0.46– 0.91). Summary estimates differed based on the study used to derive the hypothetical control group. Device deployment was unsuccessful in 6.1 % of patients, and overall complication rate was 7.1 %. Efficacy and safety were similar across LAAO device type although a majority of patients in the metaanalysis received a Watchman device. Conclusion Our data suggest that LAAO is a reasonable option for stroke prophylaxis in AF when anticoagulation is not an option, and the risk for stroke outweighs the risk of procedural complications. Data were limited with the use of most Electronic supplementary material The online version of this article (doi:10.1007/s10840-015-9988-1) contains supplementary material, which is available to authorized users. W. D. Bode : N. Patel : A. K. Gehi (*) Cardiac Electrophysiology, Division of Cardiology, CB 7075, 160 Dental Circle, 6025 Burnett-Womack Bldg, Chapel Hill, NC 27599-7075, USA e-mail: [email protected]

available devices. To better establish the risk and benefit of LAAO in comparison with standard therapy, more randomized controlled trials are necessary. Keywords Left atrial appendage . Atrial fibrillation . Stroke . Meta-analysis Abbreviations AF Atrial fibrillation LAAO Left atrial appendage occlusion

1 Introduction Atrial fibrillation (AF) is the most common dysrhythmia and is increasing in prevalence [1]. Current estimates are that AF will affect approximately 10 million people in the USA by 2050 [2]. The risk for stroke is increased 2–2.5-fold in patients with AF due to the occurrence of thromboembolic stroke, 90 % of which form in the left atrial appendage (LAA) [3, 4]. Current guidelines recommend the use of anticoagulant therapy for prevention of thromboembolic stroke in those at high risk. Prediction models have been developed to estimate the risk for stroke based on clinical variables. The most common of these risk models has been the CHADS2 score [4]. More recently, the CHA2DS2-VASc score has been suggested as an alternative in order to better delineate stroke risk in the lower-risk patient subgroups [5]. However, the decision to treat a patient with AF with anticoagulant therapy must be balanced with the risk for bleeding. Paradoxically, patients who are at the highest risk for thromboembolic stroke are also oftentimes at the highest risk for bleeding, making therapeutic decisions challenging [6]. In those with a high risk for bleeding, anticoagulation therapy may be contraindicated.


In order to reduce stroke risk without increasing bleeding risk, an alternate strategy of left atrial appendage occlusion (LAAO) has been advocated. Occlusion of the LAA was initially accomplished by oversewing of the LAA during concomitant cardiac surgery. However, minimally invasive approaches were subsequently developed. Several LAAO systems are deployed through a mini-thoracotomy approach (LAPTONI, Ethicon Endo-Surgery, Inc, Somerville, NJ, USA; AtriClip Device System—Atricure, Inc, West Chester, OH, USA; Tiger Paw System, Terumo Cardiovascular Systems, Ann Arbor, MI, USA) [7–9]. A percutaneous LAA transcatheter endocardial occlusion device (PLAATO, Appriva Medical, Inc, Sunnyvale, CA, USA) was studied in the canine model in 2002 and later done in humans [10]. Other transcatheter occlusion systems include the Amplatzer cardiac plug (ACP, St. Jude Medical, St. Paul, MN, USA) and the Watchman LAA closure device (Boston Scientific, Natick, MA, USA) [11]. The LARIAT (SentreHEART, Inc, Redwood City, CA, USA) is an alternative percutaneous transcatheter endocardial/epicardial system [12]. Several studies have been performed to evaluate the efficacy and safety of these different methods for LAAO. However, the majority of these studies have been limited by their small size and lack of a control group. In addition, disparate patient populations and differing approaches for LAAO in these studies make it challenging to gain a broad understanding of the value of LAAO. Fortunately, large outcomes data of stroke risk in nonvalvular AF provide a model for estimating stroke risk in a patient population based on clinical variables. To better understand the value of LAAO for prevention of stroke and systemic embolism, we performed a systematic review and meta-analysis of the efficacy and safety of LAAO devices in patients with nonvalvular AF.

2 Methods 2.1 Study search We performed a literature search using the PubMed and Medline databases to identify articles published between January 1, 1999 and December 31, 2013 on the benefit of LAAO device therapy for prevention of stroke or systemic embolism. The following Medical Subject Heading search terms were used: atrial appendage, follow-up studies, prospective studies, cohort studies, clinical trial [publication type], randomized controlled trial [publication type], and controlled clinical trial [publication type]. The search was restricted to English language literature and human subjects of >18 years of age. A second search of articles published by authors identified in the original search and a review of the bibliographies of the originally identified articles were used to identify any additional articles for review. Due to the need for detailed patient data,

J Interv Card Electrophysiol (2015) 43:79–89

abstracts and meeting presentations were not reviewed for inclusion. Studies were included if they met the following prespecified criteria: (1) prospective cohort study of >10 human subjects undergoing LAAO for prevention of stroke or systemic embolism in the setting of nonvalvular AF; (2) provide primary data on clinical outcomes, including the occurrence of stroke or systemic embolism and safety of the procedure; and (3) mean follow-up time≥6 months. Studies were excluded if they were a secondary analysis of previously published primary data or if patients underwent concomitant procedures, including valve surgery or atrial fibrillation ablation. Two investigators (WB and NP) independently reviewed the titles and abstracts of articles and excluded those that clearly did not meet the inclusion criteria. The full article was reviewed when necessary. A consensus was reached, including a third investigator (AG), in order to finalize the study selection. Shown in Fig. 1 is the study selection process per QUOROM guidelines [14]. 2.2 Data abstraction Two investigators (WB and NP) independently reviewed selected articles, blinded to the author, journal, and institution. Data for each article were abstracted in a standardized fashion. Any discrepancies in abstracted data were resolved by consensus including a third investigator (AG). Data abstracted from each article included eligibility criteria, study population number and demographics (including age, gender, CHADS2 score), study design, appendage closure technique and device type, use of concomitant stroke prevention therapy (i.e., aspirin, clopidogrel, warfarin, etc.), average follow-up, and outcomes. The primary outcome was incidence of stroke or systemic embolism. Secondary outcomes of interest included likelihood of successful device deployment and complications of closure procedure (tamponade, pericardial effusion, device embolization, emergent surgery, access complications, air embolism, and procedural mortality). All outcomes were analyzed according to the intention-to-treat principle whenever these data were available. 2.3 Statistical analysis Only one article [11] had a control group comparing the efficacy of LAAO to standard of care (warfarin). Therefore, an estimate of thromboembolic (i.e., not including hemorrhagic) stroke risk with various therapies (no therapy, aspirin, warfarin, or novel anticoagulants) was derived from previously published outcomes studies of Gage et al., Singer et al., Olesen et al., and data from the RE-LY, ROCKET-AF, and ARIS TOTLE trials [13, 15–20]. First, a hypothetical control group was derived based on pooled individual data [15] from 2580 participants with nonvalvular AF treated with aspirin in

J Interv Card Electrophysiol (2015) 43:79–89


PUBMED, MEDLINE databases searched for “atrial appendage” AND (“follow-up studies” OR “prospecve studies” OR “cohort studies” OR “clinical trial [publicaon type]” OR “randomized controlled trial [publicaon type]” OR “controlled clinical trial [publicaon type]”)

242 abstracts reviewed for inclusion & exclusion criteria

206 abstracts excluded: not related to appendage occlusion (n=172) trials of imaging (n=6) study design paper (n=2) case reports or case series of less than 10 paents (n=9) animal studies (n=3) sub-studies (n=4) review arcles (n=4) non-English arcles (6)

36 full papers extracted for detailed review

16 full papers included in analysis

20 full papers excluded: parcipants received concomitant valve surgery or AF ablaon (n=10) mean-follow up

Left atrial appendage occlusion for prevention of stroke in nonvalvular atrial fibrillation: a meta-analysis.

When anticoagulation for stroke prevention is contraindicated, left atrial appendage occlusion (LAAO) may be performed. Studies of LAAO have been limi...
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