Abstract
Background:
The SALUTE trial was a prospective, multicenter, single-arm trial to confirm the safety and efficacy of the WATCHMAN left atrial appendage closure (LAAC) device for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan.
Methods and Results:
A total of 54 subjects (including 12 roll-in subjects) with a WATCHMAN implant procedure were followed in 10 investigational centers. Follow-up visits were performed up to 2 years post-implant. The baseline CHA2DS2-VASc score was 3.6±1.6 and the baseline HAS-BLED score was 3.0±1.1. All 42 subjects in the intention to treat (ITT) cohort underwent successful implantation of the LAAC device without any serious complications, achieving the prespecified performance goal. The effective LAAC rate was maintained at 100% from 45 days to 12 months post-implant, achieving the prespecified performance goal. During follow-up, 1 subject died of heart failure, and 3 had ischemic strokes, but there were no cases of hemorrhagic stroke or systemic embolism. All events were adjudicated as unrelated to the WATCHMAN device/procedure by the independent Clinical Events Committee. All 3 ischemic strokes were classified as nondisabling based on no change in the modified Rankin scale score.
Conclusions:
Final results of the SALUTE trial demonstrated that the WATCHMAN LAAC device is an effective and safe alternative nonpharmacological therapy for stroke risk reduction in Japanese NVAF patients who are not optimal candidates for lifelong anticoagulation. (Trial Registration: clinicaltrials.gov Identifier NCT 03033134)
Previous trials have demonstrated that more than 90% of thrombi from the heart originate in the left atrial appendage (LAA) in patients with atrial fibrillation (AF).1
The WATCHMANTM
Left Atrial Appendage Closure (LAAC) device (Boston Scientific, St. Paul, MN, USA) is intended to permanently seal off the LAA and provides an alternative to long-term oral anticoagulation (OAC) therapy for stroke prevention. This particular device has been compared with OAC therapy in 2 randomized clinical trials: PROTECT AF (WATCHMAN LAA Closure Device for Embolic PROTECTion in Patients with Atrial Fibrillation)2
and PREVAIL (Prospective Randomized EVAluation of the WATCHMAN LAA Closure device In Patients with Atrial Fibrillation Versus Long Term Warfarin Therapy).3
The patient-level meta-analysis combining 5 years of follow-up data from these 2 trials demonstrated that device patients had comparable efficacy for LAAC vs. warfarin, had significantly fewer hemorrhagic strokes, substantially fewer disabling/fatal strokes, and fewer cardiovascular (CV) deaths than those receiving warfarin.4
Editorial p ????
It is recommended that LAA occlusion be considered for stroke prevention in patients with AF and contraindications for long-term OAC treatment (Class IIb in the 2016 European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation developed in collaboration with EACTS),5
as well as in the 2019 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) focused update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation.6
The LAAC device is also mentioned in the 2018 Japanese Circulation Society (JCS)/Japanese Heart Rhythm Society (JHRS) Guideline on nonpharmacotherapy of cardiac arrhythmias.7
The generalizability of findings from previous clinical trials into the Japanese medical environment is a key question. Thus, we conducted the SALUTE (A Study to evaluate the Safety and effectiveness of the Left atrial appendage closure therapy Using BSJ003 W for patients with non-valvular atrial fibrillation at increased risk of ThromboEmbolism in Japanese medical environment) trial to evaluate the safety and effectiveness of LAAC therapy for Japanese patients with nonvalvular atrial fibrillation (NVAF). Here, we report on the final outcomes at 2-year follow-up post-implantation.
Methods
The design of the SALUTE trial has been previously described.8
In brief, it was a prospective, multicenter, single-arm clinical trial to assess the safety and efficacy of the WATCHMAN LAAC device in patients with NVAF. The trial was conducted at 10 investigational centers in Japan and adhered to the Declaration of Helsinki, in compliance with Good Clinical Practice, with each site’s institutional review board’s approval. All subjects provided written informed consent prior to enrollment. The device was available in 5 sizes, and was implanted under transesophageal echocardiography (TEE) and angiographic guidance. After device implantation, subjects were followed up at 45 days, 6 months, 12 months, 18 months and 24 months with neurologic assessments planned and on as-needed basis for any neurologic events. TEE was performed at 45 days, 6 months and 12 months.
There were 3 co-primary endpoints in this trial: (1) periprocedural safety defined as acute events within 7 days of the procedure (major CV or endovascular complications); (2) a composite of ischemic stroke, hemorrhagic stroke, systemic embolism, and CV death (including unexplained cause); and (3) the effective LAAC rate defined as no leak >5 mm. An independent clinical events committee (CEC) adjudicated all endpoint-related events.8
Strokes were classified as disabling if associated with an increase in the modified Rankin scale (mRS) score by at least 2 points. The effective LAAC rate was independently reviewed by a TEE core laboratory. Major bleeding was defined as per Bleeding Academic Research Consortium (BARC) bleeding definitions type 3 or 5 and clinically overt nonfatal bleeding was defined as BARC bleeding definition type 2.9
Statistical Analysis
Descriptive statistics were generated for the data collected at baseline, during the procedure, and at follow-ups. For continuous variables, the mean, standard deviation (SD), number of subjects, median, range, 95% confidence interval (CI), and discrete values (frequency table and percentage) were calculated and analyzed.
All statistical analyses were done by intention to treat (ITT) for the primary cohort with subjects enrolled in the trial regardless of the success of the study device implanted. Each operator was permitted 2 nonanalyzable patients for familiarization with the procedure (roll-in subjects); however, their data were evaluated separately from that of the ITT cohort. The rates and 95% CIs of each endpoint were expressed as percentages using all subjects’ data available by 2 years’ follow-up.
Results
Subject Demographics and Follow-up Compliance
As previously reported,8
a total of 42 subjects were enrolled in the ITT cohort, and all but 1 (97.6%) completed the 2-year follow-up visit, confirming the required follow-up attendance in the study was well managed (Supplementary Figure). There was 1 death from heart failure at 505 days post-implant. Baseline characteristics of the ITT subjects and age subgroup are shown in
Table 1. The mean age was 72.5 years; the mean CHADS2
score was 2.5, the mean CHA2DS2-VASc score was 3.6, the mean HAS-BLED score was 3.0 and 42.9% (18/42) of subjects had long-term persistent AF. Of the 42 subjects enrolled in the ITT cohort, 20 were ≥75 years old and had higher stroke risk as well as bleeding risk based on the CHADS2
score (3.3), CHA2DS2-VASc score (4.6) and HAS-BLED score (3.1).
Table 1.
Subject Demographics (ITT Cohort and Age Subgroups)
| Characteristics |
ITT cohort (n=42) |
Total
(n=42) |
Age subgroups |
| <75 years (n=22) |
≥75 years (n=20) |
| Age (years) |
72.5±8.8 (42)
(50, 91) |
66.1±6.7 (22)
(50.0, 74.0) |
79.6±4.2 (20)
(75.0, 91.0) |
| Sex |
| Female |
16.7% (7/42) |
13.6% (3/22) |
20.0% (4/20) |
| Male |
83.3% (35/42) |
86.4% (19/22) |
80.0% (16/20) |
| Height (cm) |
164.2±8.2 (42)
(145.0, 179.0) |
164.7±7.1 (22)
(146.0, 179.0) |
163.8±9.4 (20)
(145.0, 178.0) |
| Weight (kg) |
68.0±13.9 (42)
(40.0, 118.2) |
71.0±16.5 (22)
(40.0, 118.2) |
64.7±9.6 (20)
(48.0, 87.0) |
| BMI (kg/m2) |
25.2±4.8 (42)
(18.0, 41.4) |
26.0±4.7 (22)
(18.8, 40.1) |
24.3±4.9 (20)
(18.0, 41.4) |
| AF pattern |
| Paroxysmal |
35.7% (15/42) |
31.8% (7/22) |
40.0% (8/20) |
| Persistent |
21.4% (9/42) |
22.7% (5/22) |
20.0% (4/20) |
| Permanent |
42.9% (18/42) |
45.5% (10/22) |
40.0% (8/20) |
| Paced |
0.0% (0/42) |
0.0% (0/22) |
0.0% (0/20) |
| Previous AF ablation |
40.5% (17/42) |
31.8% (7/22) |
50.0% (10/20) |
| CHADS2 score (continuous) |
2.5±1.3 (42)
(0.0, 6.0) |
1.8±0.9 (22)
(0.0, 4.0) |
3.3±1.3 (20)
(1.0, 6.0) |
| CHA2DS2-VASc score (continuous) |
3.6±1.6 (42)
(1.0, 8.0) |
2.7±1.0 (22)
(1.0, 5.0) |
4.6±1.6 (20)
(2.0, 8.0) |
| HAS-BLED score (continuous) |
3.0±1.1 (42)
(1.0, 5.0) |
2.8±1.2 (22)
(1.0, 5.0) |
3.1±1.0 (20)
(2.0, 5.0) |
| Risk factors |
| CHF |
52.4% (22/42) |
50.0% (11/22) |
55.0% (11/20) |
| Hypertension |
83.3% (35/42) |
86.4% (19/22) |
80.0% (16/20) |
| Diabetes |
31.0% (13/42) |
22.7% (5/22) |
40.0% (8/20) |
| Stroke/TIA/TE |
16.7% (7/42) |
9.1% (2/22) |
25.0% (5/20) |
| Vascular disease |
11.9% (5/42) |
9.1% (2/22) |
15.0% (3/20) |
| Abnormal renal function |
54.8% (23/42) |
54.5% (12/22) |
55.0% (11/20) |
| Abnormal liver function |
4.8% (2/42) |
9.1% (2/22) |
0.0% (0/20) |
| Bleeding |
9.5% (4/42) |
9.1% (2/22) |
10.0% (2/20) |
| Labile INRs |
7.1% (3/42) |
13.6% (3/22) |
0.0% (0/20) |
| Drugs/alcohol |
33.3% (14/42) |
27.3% (6/22) |
40.0% (8/20) |
Values are mean±SD (n) (minimum, maximum) or % (n/N). AF, atrial fibrillation; CHF, congestive heart failure; INR, international normalized ratio; TE, thromboembolic event; TIA, transient ischemic attack.
The effective LAAC rate was 100% of the subjects at 45 days (42/42), 6 months (42/42) and 12 months (41/41) post-implant (Table 2); 1 subject missed the 12-month visit because of an unrelated hospitalization at another facility. The largest residual peri-device jet was 4.0 mm at 12 months. There were no subjects with residual peri-device flow >5 mm at 45 days, 6 months or 12 months. Success of the 3rd co-primary endpoint was achieved, as the rate was higher than the prespecified performance goal of 94.0%.
Table 2.
Effective LAAC and Warfarin Discontinuation Results (ITT Cohort)
Third co-primary endpoint
(effective LAAC rate assessed by the TEE Core Laboratory) |
45 days |
6 months |
12 months |
| Effective LAAC rate (jet size ≤5 mm) |
100% (42/42) |
100% (42/42) |
100% (41/41) |
| Jet size >5 mm |
0.0% (0/42) |
0.0% (0/42) |
0.0% (0/41) |
| Size of largest residual jet around device (mm) |
2.8±0.8 (1.0, 4.0) |
2.5±0.6 (2.0, 4.0) |
2.6±0.8 (1.0, 4.0) |
| Warfarin discontinuation rate by visit |
97.6% (41/42) |
95.2% (40/42) |
95.1% (39/41) |
Values are mean±SD (minimum, maximum) or % (n/N). Note: the effective LAAC rate defined as peri-device flow ≤5 mm assessed by the independent TEE Core Laboratory. The performance goal of the third co-primary endpoint was 94.0%, derived from the effective LAAC rate observed in the PROTECT AF and PREVAIL trials, confirming successful endpoint was achieved. ITT, intention to treat; LAAC, left atrial appendage closure.
Warfarin was discontinued when the TEE indicated complete LAA seal or a residual jet flow ≤5 mm around the device; all (42/42) subjects discontinued warfarin at least once over the course of follow-up based on effective LAA seal. The warfarin discontinuation rate at each time point was 97.6% (41/42) at 45 days, 95.2% (40/42) at 6 months, and 95.1% (39/41) at 12 months (Table 2). At 45 days, 1 subject continued warfarin despite LAA seal due to deep vein thrombosis unrelated to the study procedure or device and stopped warfarin at 6 months. At 6 months, 2 subjects (who had discontinued warfarin at 45 days) restarted warfarin from 6 months through the 12-month visit due to a device-related thrombus and both of them discontinued after thrombus resolution. Concomitant medication therapy in the trial is shown in
Supplementary Table.
Composite Events
As shown in
Table 3
and
Figure 1, there were 3 cases of ischemic stroke and 1 case of CV death during the 2-year post-implant period. No hemorrhagic strokes or systemic embolisms were reported. The CV death occurred at 505 days post-implant and autopsy was not performed because the subject died at home. The cause of death was considered to be heart failure based on the subject’s medical history and comorbidities (i.e., congestive heart failure, coronary artery disease, drug-eluting stent implanted and angina). The ischemic strokes occurred at 118, 296 and 478 days post-implant, respectively. In 1 case of ischemic stroke lacunar infarction was suggested on MRI, but hospital admission was not required. In the other 2 cases, there was a prior cerebral infarction that may have existed prior to trial enrollment in 1 case and no admission or further treatment was required and in the other case transient ischemic attack was diagnosed because repeat MRI showed resolution of the stenosis and neurological symptoms resolved with heparin administration. No evidence of device-related thrombus was observed on either the scheduled and/or post-stroke TEE in any case. In addition, all strokes were defined as nondisabling stroke because there was no change in the mRS score post-stroke. More detailed descriptions of these endpoint events are presented in
Table 4.
Table 3.
Composite Endpoints Results Through 2 Years Post-Implant (ITT Cohort)
| Endpoint events component |
% (n/N) |
95% CI |
Age subgroups |
| <75 years (n=22) |
≥75 years (n=20) |
| All strokes |
7.1% (3/42) |
[1.5%, 19.5%] |
9.1% (2/22) |
5.0% (1/20) |
| Ischemic stroke |
7.1% (3/42) |
[1.5%, 19.5%] |
9.1% (2/22) |
5.0% (1/20) |
| Hemorrhagic stroke |
0.0% (0/42) |
[0.0%, 8.4%] |
0.0% (0/22) |
0.0% (0/20) |
| Disabling/fatal stroke |
0.0% (0/42) |
[0.0%, 8.4%] |
0.0% (0/22) |
0.0% (0/20) |
| Nondisabling stroke |
7.1% (3/42) |
[1.5%, 19.5%] |
9.1% (2/22) |
5.0% (1/20) |
| Systemic embolism |
0.0% (0/42) |
[0.0%, 8.4%] |
0.0% (0/22) |
0.0% (0/20) |
| Cardiovascular death |
2.4% (1/42) |
[0.1%, 12.6%] |
0.0% (0/22) |
5.0% (1/20) |
| Unexplained death |
0.0% (0/42) |
[0.0%, 8.4%] |
0.0% (0/22) |
0.0% (0/20) |
Note: strokes were classified as disabling if associated with an increase in the modified Rankin Scale score by at least 2 points. CI, confidence interval; ITT, intention to treat.
Table 4.
Composite Endpoint Events Description (ITT Cohort)
| Case no. |
Demographics |
CEC adjudicated event |
LAA closure |
Event description |
| (a) |
66 years, male, long-term
persistent AF, CHA2DS2-VASc:
3, HAS-BLED: 2, Spontaneous
echo contrast |
Nondisabling ischemic
stroke at 118 days
post-implant |
TEE at 45 days
showed complete
LAA seal |
Weakness of the left leg; MRI showed
lacunar infarction; no device thrombus on
TEE
No admission required & apixaban started |
| Unrelated to device |
| (b) |
91 years, male, long-term
persistent AF. CHA2DS2-VASc:
5, HAS-BLED: 3, asymptomatic
carotid artery disease |
Nondisabling ischemic
stroke at 296 days
post-implant |
TEE 45 days
showed complete
LAA seal |
MRI showed small, old asymptomatic
cerebral infarction; no device thrombus on
TEE
No admission & no treatment required |
| Unrelated to device |
| (c) |
66 years, male, persistent AF,
CHA2DS2-VASc: 2, HAS-BLED:
3, previous AF ablation |
Nondisabling ischemic
stroke occurred at 478
days post-implant |
Residual jet size
around device
2 mm at 45 days
and at 1 year,
respectively |
TIA with intracranial stenosis on MRI;
repeat MRI showed resolution of stenosis
and neurological symptoms recovered with
heparin. No device thrombus on TEE.
Apixaban started |
| Unrelated to device |
| (d) |
80 years, male, Long-term
persistent AF, CHA2DS2-VASc: 4,
HAS-BLED: 3, angioplasty, stenting
for CAD, stable angina, CHF |
Cardiovascular death
occurred at 505 days
post-implant |
TEE images at 1
year showed
complete LAA
seal |
Died at home, no autopsy performed.
Cause of death probable heart failure
based on medical history and comorbidities |
| Unrelated to device |
Note: Case numbers correspond to those in Figure 1. CAD, coronary artery disease; CEC, Clinical Events Committee; CHF, congestive heart failure; ITT, intention to treat; LAA, left atrial appendage; MRI, magnetic resonance imaging; TEE, transesophageal echocardiography.
Over the course of 2 years’ follow-up, there were 2 cases of major bleeding (major bleed requiring transfusion and traumatic subarachnoid hemorrhage) occurring at 175 days and 318 days post-implant, respectively. In both cases the patients were over 75 years of age. One patient had a major bleed requiring transfusion in the setting of bladder cancer. The other patient had a traumatic subarachnoid hemorrhage without stroke due to sick sinus syndrome and a fall. There were 3 cases of clinically overt nonfatal bleeding (hematuria, hematoma and groin puncture bleeding) (Tables 5,6; Figure 2).
Table 5.
Bleeding Events Through 2 Years Post-Implant (ITT Cohort)
| Endpoint events |
% (n/N) |
95% CI |
Age subgroups |
| <75 years (n=22) |
≥75 years (n=20) |
| Major bleeding |
4.8% (2/42) |
[0.6%, 16.2%] |
0.0% (0/22) |
10.0% (2/20) |
| Clinically overt nonfatal bleeding |
7.1% (3/42) |
[1.5%, 19.5%] |
9.1% (2/22) |
5.0% (1/20) |
| Major bleeding events component |
Subjects (n) |
Days post-implant |
Subjects (n) |
Subjects (n) |
| Cranial bleed – without stroke |
1 |
318 |
0 |
1 |
| Major bleed requiring transfusion |
1 |
175 |
0 |
1 |
| Clinically overt nonfatal bleeding events component |
Subjects (n) |
Days post-implant |
Subjects (n) |
Subjects (n) |
| Hematuria |
1 |
12 |
1 |
0 |
| Hematoma |
1 |
22 |
1 |
0 |
| Groin puncture bleeding |
1 |
4 |
0 |
1 |
Note: major bleeding defined as per BARC bleeding definition type 3 or type 5. Clinically overt nonfatal bleeding defined as per BARC bleeding definition type 2. CI, confidence interval; ITT, intention to treat.
Table 6.
Major Bleeding Events Description (ITT Cohort)
| Case no. |
Demographics |
Event and drug regimen
at the time of bleeding |
Event description |
| (e) |
79 years, male, paroxysmal AF,
CHA2DS2-VASc: 6, HAS-BLED:
4, previous ischemic stroke,
bladder cancer |
BARC type 3b major bleeding
occurred 175 days post-implant |
Hematuria and anemia due to bladder cancer
Hospitalization required for hemorrhagic shock
DAPT discontinuation, bladder embolization, right
renal artery embolization and blood transfusion were
performed. Anemia improved and patient discharged |
Aspirin and clopidogrel were
administered (no anticoagulant) |
| (f) |
76 years, female, persistent AF,
CHA2DS2-VASc: 4, HAS-BLED:
2, spontaneous echo contrast,
sick sinus syndrome (SSS) |
BARC type 3c major bleeding
occurred 318 days post-implant |
Syncope and fall occurred due to SSS. Traumatic
subarachnoid hemorrhage without stroke occurred.
After aspirin discontinued, hemorrhage disappeared
on CT |
Aspirin was administered (no
anticoagulant) |
Note: case numbers correspond to those in Figure 2. BARC, Bleeding Academic Research Consortium; CT, computed tomography; DAPT, dual antiplatelet therapy; ITT, intention to treat.
In the ITT cohort, 2 cases of device thrombi (2/42) were reported and both resolved with warfarin therapy. In both subjects, spontaneous echo contrast was present on the screening TEE. One case of device thrombus was detected at 125 days post-implant after electrical cardioversion had been performed to treat heart failure, and warfarin therapy was continued until resolution of the thrombus at 12 months’ follow-up TEE (352 days). The other case of device thrombus was detected on 6-month follow-up TEE (166 days) and by day 264 it had resolved with warfarin therapy. Following resolution in that subject, another device thrombus was observed on the 12-month follow-up TEE (355 days) and again resolved by day 453 with warfarin therapy. Neither subject experienced associated ischemic events.
Discussion
SALUTE is the first prospective clinical trial reporting on 2-year follow-up outcomes of LAAC therapy with the WATCHMAN device in Japanese patients with NVAF. Importantly, half of the population in the ITT cohort was Japanese subjects aged ≥75 years with higher stroke risk as well as bleeding risk. In a previous publication,8
we reported a procedural success rate of 100% (42/42) without any serious device- or procedure-related complications. Beyond the procedure, these follow-up data support the efficacy of LAAC therapy as a safe alternative nonpharmacological therapy in the Japanese medical environment.
Effective LAAC Rate
The effective LAAC rate was 100% closure at 45 days and maintained at 100% through the 12 months post-implant, indicating the LAAC device created a permanent seal of the LAA in these Japanese patients. We previously reported that the 30-mm device was implanted most frequently in SALUTE.8
Recently, the WASP registry reported that the mean LAA diameter was significantly larger in Asians and the median device size used was 27 mm for Asians vs. 24 mm for non-Asians,10
suggesting that the LAA in Asians might be larger than in other races.
Mortality
In the ITT cohort there was 1 CV death (1/42) reported during the 2-year follow-up; the CEC adjudicated it as unrelated to the device or procedure. The rate of CV death in SALUTE was lower than in the EWOLUTION registry,11
which is the largest prospective real-world registry of 2-year follow-up outcomes of the WATCHMAN device.
Thromboembolic Events
There were 3 ischemic strokes (3/42) during the 2 years post-implant. After reviewing the TEE and MRI/CT images, the CEC adjudicated that none of the cases of stroke was related to the LAAC device or procedure. Also, none of the ischemic strokes was classified as disabling based on mRS score assessment, which suggests that closing the LAA could suppress formation of a large thrombus and therefore prevent the occurrence of more debilitating strokes. These results are consistent with previous evidence from the PROTECT AF and PREVAIL trials in which there were substantially fewer disabling/fatal strokes with LAAC therapy compared with warfarin therapy (hazard ratio: 0.45; P=0.034).4
Bleeding Events
There were 2 cases of major bleeding in the 2-year follow-up, but neither was adjudicated by the independent CEC as procedure- or device-related. In both cases the patients recovered without any residual impairment. Importantly, these subjects had already discontinued warfarin therapy at the 45-day follow-up visit, possibly minimizing the severity of the bleeding events. No hemorrhagic strokes were observed during the 2 years’ follow-up. Compared with the rate of major bleeding in the J-ROCKET AF trial (3.00%/year in the rivaroxaban group, 3.59%/year in the warfarin group),12
LAAC therapy is likely to lower the bleeding risk in Japanese NVAF patients. In addition, the subjects enrolled in the trial had increased bleeding risk: the mean HAS-BLED score was 3.0. The major bleeding rate in this trial was 4.8%, which was relatively lower than the expected rate of approximately 7.5% in a population with a HAS-BLED score of 3.13
As the bleeding risk from OAC increases over the patient’s lifetime, the 10-year bleeding risk in a population with a HAS-BLED score of 3 would be conservatively estimated at >45.0%.14
As Japanese patients tend to have higher rates of hemorrhagic stroke and higher bleeding risk,15
LAAC therapy may be even more beneficial than in other races.
Device Thrombus
There is potential for thrombus formation on the surface of the device, mainly on the exposed metal hub. Prevention of device thrombus is critical in the initial phase after successful implantation. Once device thrombus is identified by TEE, therapeutic anticoagulation should be resumed immediately to prevent thromboembolism. There were 2 cases of device thrombus observed in the trial, but both were finally resolved with warfarin therapy and associated ischemic events were not reported. The prevalence of device thrombus in the trial is consistent with previously reported rates.16
To protect against device thrombus, further studies are needed to determine the optimal regimens of antithrombotic medication for Japanese patients after implantation of a device.
Study Limitations
As SALUTE was a single-arm clinical trial, there is no direct comparison with standard medication therapy, including warfarin and direct oral anticoagulants, and this limits full assessment of this therapy in the Japanese patient population. In the trial, the device implanters in 10 centers were proctored by very experienced operators, and this could have contributed to the low complication rate and high effective LAA closure rate. Furthermore, although the inclusion and exclusion criteria for the trial are similar to those of previous LAAC trials, the applicability of these data needs to be corroborated by carefully conducted real-world registries in Japan.
Conclusions
Final results of the SALUTE trial demonstrated that the WATCHMAN LAAC device is an effective and safe alternative nonpharmacological therapy for stroke risk reduction in Japanese NVAF patients who are not optimal candidates for lifelong anticoagulation.
Acknowledgments
The authors thank the patients, investigators, trial site staff, and Boston Scientific Inc. employees involved in the trial for their cooperation, and Nicole Gordon (Boston Scientific Inc.) for assistance in manuscript preparation.
Data Availability
The de-identified participant data will not be shared. Boston Scientific’s Data Sharing Policy can be accessed at http://www.bostonscientific.com/en-US/data-sharingrequests.html.
Funding
This research was supported and sponsored by Boston Scientific Inc., which as the sponsor designed the trial, monitored sites, and collected and analyzed the data.
Disclosures
Dr. Aonuma had endowed departments by Boston Scientific Japan, Japan Lifeline Co., Ltd., Nihon Cohden Corporation, Biotronik Japan, Inc., Toray Industries, Inc., Boehringer Ingelheim GmbH, and Century Medical, Inc., received lecture fees from Boehringer Ingelheim GmbH, Medtronic Japan Co., Ltd., Daiichi Sankyo Co., Ltd., and Abbott Medical Japan Co., Ltd., and received scholarship donations from Otsuka Pharmaceutical Co., Ltd., Astec Co., Ltd. Astellas Pharma Inc., Johnson & Johnson, Takeda Pharmaceutical Co., Ltd., Teijin Pharma Limited, Shionogi & Co., Ltd., Medical Corporation Tsukuba Kinenkai, and Abbott Medical Japan Co., Ltd. Dr. Ando received lecture fees from Boston Scientific Japan, Dr. Morino received a research grant from Boston Scientific Japan, Mr. Gomi is an employee of Boston Scientific Japan, and Dr. Uchida provided consultation to Boston Scientific Japan. Dr. Yamasaki, Dr. Nakamura, Dr. Matsumoto, Dr. Hirao, Dr. Goya, Dr. Hayashida, Dr. Kusano, Dr. Main, Dr. Saito, and Dr. Takayama report no conflicts of interest.
Drs Aonuma, Morino and Hayashida are the members of the Editorial Board of
Circulation Journal.
Financial Disclosure
The SALUTE trial was sponsored and funded by Boston Scientific Corporation.
Institutional Review Board / Ethics Committee
University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki 305-8576, Japan. Phone: +81-29-853-3914, Facsimile: +81-29-853-5669, Reference number: 16-77.
Supplementary Files
Please find supplementary file(s);
http://dx.doi.org/10.1253/circj.CJ-20-0196
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