Percutaneous Left Atrial Appendage Occlusion in Atrial Fibrillation Patients With a Contraindication to Oral Anticoagulation

A Focused Review

Marin Nishimura; Shiv Sab; Ryan R. Reeves; Jonathan C. Hsu

Disclosures

Europace. 2018;20(9):1412-1419. 

In This Article

Watchman™

The Watchman LAAO device (Boston Scientific, Marlborough, MA, USA) is a self-expanding nitinol occlusion cage with 10 peripheral fixation anchors deployed in the LAA using trans-septal approach (Figure 1). According to the manufacturer, measured maximum LAA ostium width must be 17–31 mm and the LAA depth must be at least as long as the LAA ostium width in order to accommodate available Watchman sizes.[16] Since its development in 2002, the Watchman was Conformité Européene (CE) approved in 2005 and more recently became the only LAAO-specific device to receive approval by the FDA in July 2015. Data regarding safety and efficacy from some of the studies are summarized in Table 1.[17–23] The pivotal Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation (PROTECT AF) study was the first RCT of any LAAO.[17] Seven hundred and seven patients with non-valvular AF were randomly assigned to either LAAO with Watchman or conventional warfarin therapy. Patients with contraindication to anticoagulation were excluded from the study as the patients were required to undergo 45 days of oral anticoagulation post-procedure. At mean follow-up of 3.8 years, the Watchman device was shown to be non-inferior to warfarin in terms of efficacy as defined by reduction of stroke and systemic embolism [2.3 vs. 3.8 events per 100 patients-years, rate ratio (RR): 0.60, 95% credible interval (CrI) 0.41–1.05]. The study also established improvements in cardiac (HR: 0.40, 95% CI: 0.21–0.75; P = 0.005) as well as all-cause mortality (HR: 0.66, 95% CI: 0.45–0.98; P = 0.04) in the Watchman arm. However, there was a significantly higher risk of safety events (pericardial effusion, major bleeding, procedure-related stroke, device embolization, or haemorrhagic stroke, 7.4 vs. 4.4 per 100 patient-years in the Watchman arm vs. dose-adjusted warfarin, RR: 1.69, 95% CI: 1.01–3.19) which occurred early, either peri- or post-procedurally. Device embolization was seen in 0.6% of patients. The second Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients with Atrial Fibrillation vs. Long-Term Warfarin Therapy (PREVAIL) study was conducted in accordance to recommendations by the FDA because of safety and selection concerns of the original study.[20] The PREVAIL trial showed significant improvement of procedural complications compared with the initial PROTECT AF. The first primary endpoint of composite of stroke, systemic embolism, or unexplained death did not meet pre-specified margin for non-inferiority; however, the second co-primary endpoint of stroke or systemic embolism 1 week after randomization was statistically non-inferior to warfarin therapy. Furthermore, in the Continued Access Registry of the initial PROTECT AF trial, patients who underwent device implantation as part of the PROTECT AF trial were compared with a subsequent non-randomized registry of patients undergoing Watchman implantation (n = 542 vs. n = 460).[21] As a result, a significant decline in the rate of procedure- or device-related safety events across the two studies were observed (7.7% vs. 3.7% of patients, P = 0.007) likely as a consequence of increased operator experience.

Figure 1.

Left atrial appendage occlusion devices. (A) Watchman. Image provided courtesy of Boston Scientific. © 2017 Boston Scientific Corporation or its affiliates. All rights reserved. (B) Amplatzer Amulet. Image provided courtesy of Abbot. All rights reserved. (C) Lariat. Image provided courtesy of SentreHEART.

To address the safety and efficacy of Watchman in patients who are not eligible for warfarin therapy due to contraindications to oral anticoagulation, the ASA Plavix Feasibility Study with Watchman Left Atrial Appendage Closure Technology (ASAP) Study was conducted, in which 150 patients with non-valvular AF underwent LAAO with the Watchman device without warfarin transition. Patients were treated with 6 months of dual antiplatelet therapy (DAPT) followed by life-long aspirin. History of haemorrhagic/bleeding tendencies (93%) was the most common reason for warfarin ineligibility. The study observed 64% reduction in stroke risk predicted based on patients' risk factors.[22] Observed rate of systemic embolism or stroke was 2.3% per year (vs. expected rate of 7.3% per year). The authors concluded that LAAO with the Watchman may be safely performed without a warfarin transition and might be safe and effective in AF patients with contraindications to anticoagulation.

The more recent EWOLUTION registry reported clinical data of 1021 subjects with relatively high risk of stroke (average CHADS score: 2.8 ± 1.3) and moderate-to-high risk of bleeding (average HAS-BLED score: 2.3 ± 1.2) who underwent LAAO with the Watchman device. Notably, 62% of these subjects were deemed unsuitable for anticoagulation with NOACs by their provider. Method of anticoagulation or antiplatelet therapy following the procedure varied, with 73% of the subjects not receiving warfarin. These subjects most commonly received DAPT for 6 months (59%). Despite being in a high-risk population, LAAO with the Watchman device in this registry had a high success rate (98.5%) with low periprocedural risk and low 30 days of mortality of 0.7%.[23] Implant success was similar whether patients were eligible for anticoagulation or not (98.4% vs. 98.7% for those eligible and not eligible, respectively, P = 0.794). The incidence of serious adverse events did not differ based on patient eligibility for anticoagulation. Hence, prior studies have suggested that implantation of the Watchman device may be successfully and safely performed in a wide variety of real-world scenarios, possibly even in patients with contraindications to all anticoagulation. However, no prospective comparison study of Watchman with no post-procedural anticoagulation has been performed, and therefore the overall risk of device thrombosis and risk of device-related thromboembolism when no post-procedural oral anticoagulation is prescribed remains unknown.

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