Editorials
2-Year Outcomes of Left Atrial Appendage Occlusion With WATCHMAN in Japanese Atrial Fibrillation Patients
2020 Volume 84 Issue 8 Pages 1227-1229
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2020 Volume 84 Issue 8 Pages 1227-1229
Atrial fibrillation (AF) causes stagnant blood flow within the left atrium, leading to thrombus formation and cardiogenic stroke. Almost 90% of all thrombi localize in the left atrial appendage (LAA). Oral anticoagulation (OAC) prevents LAA thrombus in patients with non-valvular AF (NVAF), but these drugs are unfavorable in NVAF patients with higher bleeding risk, presenting physicians with a therapeutic dilemma.
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WATCHMAN (Boston Scientific, St. Paul, MN, USA) is the most extensively studied LAA occlusion (LAAO) device and the only one that has been approved in Japan. In North American and European trials, LAAO with the WATCHMAN demonstrated stroke prevention in NVAF patients, comparable to warfarin with additional reductions in major bleeding and death (Figure 1).1–4 However, little information is available regarding Asian patients.
Meta-analysis of 5-year outcomes from PROTECT AF and PREVAIL trial cohorts. Patients treated with the WATCHMAN were compared with those treated with warfarin. Disabling was defined as an increase in the Modified Rankin Score by at least 2 points. CI, confidence interval; SE, systemic embolism. (Reproduced with permission from Reddy VY, et al.4)
Aonuma et al conducted the SALUTE trial, a multicenter single-arm prospective registry, to evaluate the safety and efficacy of LAAO with the WATCHMAN in Japanese NVAF patients (n=42).5 After implantation of the device, warfarin was administered for 45 days and was stopped when effective LAAO (peri-device flow ≤5 mm) was confirmed by transesophageal echocardiography. Thienopyridine and aspirin were then prescribed, allowing time for endothelialization on the device surface. The first results reported that the device was successfully implanted in all patients.5 In this issue of the Journal, Aonuma et al report the 2-year outcomes of the SALUTE trial, including the incidence of ischemic stroke, major bleeding, and all-cause death.6 Because of a paucity of data on LAAO in Asian countries, the present results are clinically important, especially in Japan.
In previous North American/European studies, the rate of major bleeding in LAAO with WATCHMAN has been 0.4–3.5% (events per 100 patient-years, Figure 2).1–3 A meta-analysis demonstrated that WATCHMAN reduced the risk of major bleeding, particularly hemorrhagic stroke, more than warfarin (Figure 1).4 In Asian countries, the prevalence of major bleeding was 1.0% in the WASP registry and 0.6% in a Korean registry.7,8 In the SALUTE trial, the major bleeding rate was approximately 2.4% (2 events/84 patient-years, Figure 2).6 The incidence of major bleeding in Asian patients was similar to that in North American/European patients. Asian patients inherently have a higher bleeding risk than non-Asian patients, posing a clinical conundrum for AF patients on OAC, and may take advantage of LAAO more than non-Asian patients in terms of preventing major bleeding.
Pivotal studies of left atrial appendage occlusion with the WATCHMAN device. *18-month event rate. **Events included ischemic stroke, transient ischemic attack, and systemic embolism. †Pooled data from patients with Amplatzer cardiac plug and WATCHMAN. ‡Event rates estimated from the original data in the study. RCT, randomized controlled study.
In the North American/European studies, the incidence of ischemic stroke was reportedly 1.0–2.3% with WATCHMAN treatment (Figure 2),1–3 showing non-inferiority to warfarin treatment (Figure 1).4 However, in the SALUTE trial, the estimated ischemic stroke rate was approximately 3.6% (3 events/84 patient-years, Figure 2), which appears higher than the rate in the North American/European studies.6 A potential explanation for the ischemic stroke finding is incomplete LAAO by the WATCHMAN. Although recognized as effective for LAAO, even small peri-device flow (≤5 mm) may affect thrombus formation especially after discontinuation of warfarin. The percentage of complete LAAO appeared to be lower in the SALUTE trial (59.5%) compared with previous studies (e.g., 91.4% in the EWOLUTION trial).3,5 A previous study demonstrated that peri-device flow did not increase thromboembolic risk during 1-year follow-up,9 but there was a case of thrombus associated with peri-device flow 2 years after implantation.10 The association between incomplete LAAO and thromboembolic risks remains to be elucidated. In the WASP registry, Asian patients had a larger LAA ostial diameter than non-Asian patients (23.4±4.1 mm vs. 21.2±3.1 mm) and a similar diameter was reported in the SALUTE trial (23.6±2.6 mm).5,7 Appropriate positioning of a correctly sized device may be particularly important in Asian patients with their larger LAA to avoid peri-device leakage and thromboembolic events.
Another potential explanation of the ischemic stroke is device-related thrombus (DRT); that is, thrombus created on the device surface. Implantation of foreign material increases thrombogenesis. In the SALUTE trial, 2 patients had DRT and restarted warfarin treatment; DRT resolved and no thromboembolic events occurred.6 However, the time course of DRT is still not understood. Endothelialization may take longer to fully cover the device surface. DRT can occur even in patients without peri-device leakage. A recent study reported that the incidence of DRT was low (3.8%) but that it was significantly associated with ischemic stroke risk.11 The optimal management of DRT should be examined. Nevertheless, 3 patients with ischemic stroke in the SALUTE trial recovered without any physical disability, as reported in previous studies, which may be an advantage of LAAO with the WATCHMAN.4,6
LAAO with the WATCHMAN has shown long-term benefit over warfarin therapy and will be an alternative to conventional OAC in NVAF patients.4 However, there are still unresolved issues with this treatment. First, non-vitamin K-dependent oral anticoagulants (NOACs) have become the standard for OAC in NVAF patients, but there are no direct comparisons of the WATCHMAN and NOACs. Second, the LAA is a nest for thrombus but may also play a role in neurohormonal and hemodynamic regulation. In a recent study, epicardial LAAO (Lariat, LAA exclusion) decreased blood pressure compared with endocardial LAAO (WATCHMAN, LAA occlusion).12 The physiological role of the LAA needs to be examined. Third, the LAA is a potential arrhythmogenic substrate and hybrid ablation therapy combined with WATCHMAN treatment may improve the outcomes. Fourth, there are different stroke/bleeding epidemiologies among races; region-specific optimization of LAAO treatment is required. As the SALUTE trial reported, it would be worthwhile to examine Asian-specific responses to LAAO with the WATCHMAN to ensure that this technology is successfully deployed in Asia.
M.H. received speaker fees from Nippon Boehringer Ingelheim, Daiichi-Sankyo, and Johnson & Johnson.
