Antithrombotic Regimen After Percutaneous Left Atrial Appendage Closure　― A Real-World Study ―

Abstract

Background: Antithrombotic therapy after left atrial appendage closure (LAAC) in patients at high risk of bleeding remains controversial. We present real-world clinical outcomes of LAAC.

Methods and Results: Data from 74 consecutive patients who received LAAC therapy between January 2020 and June 2022 were analyzed. Patients received 1 of 3 antithrombotic therapies according to the bleeding risk category or clinical event. Regimen 1 was based on a prior study, regimen 2 comprised a lower antiplatelet drug dose without dual antiplatelet therapy, and regimen 3 was antiplatelet drug administration for as long as possible to patients with uncontrollable bleeding who were required to stop anticoagulant drugs. Overall, 73 (98.6%) procedures were successful. Of them, 16 (21.9%) patients were selected for regimen 1, 46 (63.0%) for regimen 2, and 11 (15.1%) for regimen 3. Device-related thrombosis (13% vs. 0% vs. 0%, P=0.0257) only occurred with regimen 1. There was no difference in major bleeding event rates (6% vs. 2% vs. 9%, P=0.53).

Conclusions: The post-LAAC antithrombotic regimen was modified without major concerns.

Cardioembolic stroke is the most common adverse event in patients with atrial fibrillation (AF). Oral anticoagulants (OAC) are the gold standard for preventing stroke and systemic embolism, but some patients have contraindications to OAC therapy due to a high bleeding risk (HBR). In September 2019, the WATCHMAN^TM left atrial appendage closure (LAAC) device (Boston Scientific, St. Paul, MN, USA) was commercially introduced in Japan as an alternative to anticoagulation therapy. In Japan, LAAC is approved for patients with nonvalvular AF (NVAF), long-term OAC use, and HBR (HAS-BLED score ≥3, a history of Bleeding Academic Research Consortium [BARC] type 3 bleeding, requiring dual antiplatelet therapy [DAPT] for ≥1 year, multiple episodes of falls requiring interventions, or a history of cerebral amyloid angiopathy).^1–3 However, anticoagulation therapy is required after the procedure to prevent device-related thrombosis (DRT), and the use of antithrombotic drugs after WATCHMAN implantation in patients with HBR is controversial. Patients with previous stroke/transient ischemic attack within 90 days of enrollment have been excluded from previous large clinical studies,^4,5 so in many cases, the complete U.S. Food and Drug Administration (FDA)-approved postprocedural treatment protocols studied in pivotal trials of WATCHMAN are rarely adhered to and are adjusted for individual patients.⁶ Findings from a large cohort study and meta-analysis on the safety and efficacy of postprocedural antithrombotic therapy at discharge are available, but few reports of long-term outcomes have been published.^7,8 The safety and efficacy of various antithrombotic regimens have been reported in small trials in other Western countries but these may result in an overdose in smaller-stature Japanese patients especially.⁹ LAAC may become more widely used in Japan, and there is, therefore, a need for appropriate antithrombotic therapy for the Japanese population.¹⁰

The aim of the present study was to discuss the safety and efficacy of reduced-dose postoperative antithrombotic therapy, especially in patients with HBR.

Methods

Study Design and Population

This prospective study included all patients who underwent LAAC at the Chiba University Hospital between January 2020 and June 2022. Data on the patients’ baseline characteristics, procedure details, and imaging findings were extracted from medical records indexed at discharge. Data on antithrombotic therapies and adverse events were collected at the time of follow-up assessments. This study was approved by the Ethical Committee of the Chiba University Graduate School of Medicine (approval no. 4013) and was conducted in accordance with the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. All patients signed a written consent form at the time of the procedure.

In total, 73 (98.6%) patients undergoing LAAC were administered antithrombotic therapy to allow time for device endothelialization. Therapy was based on the SALUTE trial, a clinical study to confirm the safety and efficacy of LAAC in Japan,^11,12 and modified according to bleeding risk categories or clinical events (Figure 1). Regimen 1 was the Instruction For Use (IFU)-listed regimen based on the SALUTE trial,^11,12 but direct OAC (DOAC) was also allowed. Regimen 2 was a modified regimen involving reduced antiplatelet drug doses without DAPT. However, patients were allowed to take a DOAC for 3 months with or without an antiplatelet drug after LAAC. This regimen is in use in the ongoing CHAMPION-AF trial, which is a prospective, randomized, multicenter global investigation to determine if LAAC with the WATCHMAN FLX^TM device is a reasonable alternative to non-vitamin K OAC in patients with NVAF. Regimen 2 was given to patients with controllable bleeding; that is, not life threatening and not requiring periodic blood transfusions. In contrast, uncontrollable bleeding is life-threatening bleeding that requires transfusions and is either difficult to fundamentally resolve or requires intervention or surgery for fundamental resolution, such as diverticular bleeding. Regimen 3 involved the administration of antiplatelet drugs for as long as possible to patients with uncontrollable bleeding or hemodialysis with prior coronary artery disease and cardiogenic stroke who were required to stop anticoagulant drugs.

Figure 1.

Three treatment regimens used in this study. ASA, acetylsalicylic acid; CT, computed tomography; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; IFU, Instruction For Use; OAC, oral anticoagulant; SAPT, single antiplatelet therapy; TEE, transesophageal echocardiography; WF, warfarin.

We collected the recorded baseline characteristics focusing on risk scores for bleeding (HAS-BLED score) and thromboembolism (CHADS₂ and CHA₂DS₂-VASc scores). The presence of chronic dialysis, renal transplantation, or serum creatinine level >200 μmol/L was classified as abnormal renal function, according to the HAS-BLED score. Similarly, abnormal liver function was categorized as chronic hepatic disease (e.g., cirrhosis) or based on biochemical evidence of significant hepatic derangement (e.g., bilirubin >2×upper limit of normal, in association with aspartate aminotransferase/alanine aminotransferase/alkaline phosphatase >3×upper limit of normal).^13,14 Follow-up imaging was performed if drugs were changed, with simultaneous and more frequent clinical follow-up if necessary. Bleeding events were scored according to the BARC definition of bleeding. Major bleeding was defined as type 3 or type 5. Other events and complications were defined according to the Munich consensus document.¹⁵ Follow-up transesophageal echocardiography (TEE) was performed for patients who underwent LAAC in the early period of this study: those with severe chronic kidney disease (defined as estimated glomerular filtration rate <15 mL/min/1.73 m²), but had not yet undergone hemodialysis. CT examination was performed instead of or in conjunction with follow-up TEE. Follow-up imaging was performed before changing antithrombotic medication in accordance with the SALUTE trial.^11,12

Statistical Analysis

Categorical variables are expressed as frequencies and percentages. Continuous variables, if normally distributed, are presented as mean and standard deviation or, for skewed distributions, as median and interquartile range. Analyses were performed using the Mann-Whitney U, Kruskal-Wallis, chi-squared, or Fisher exact probability tests, as suitable. Two-tailed P values <0.05 were considered statistically significant. Statistical analyses were performed using JMP® 10.0.0 (SAS Institute Inc., Cary, NC, USA).

Results

We included 74 consecutive patients treated between January 2020 and June 2022 in this study. The WATCHMAN 2.5^TM and WATCHMAN FLX devices were implanted in 39 and 34 patients, respectively; there was 1 case in which the fit of the device for a large LAA was poor and classified as unsuccessful. No patient met the exclusion criteria of the Japanese Circulation Society guideline on the proper use of WATCHMAN.³ The median follow-up period was 402 (196–502) days. Ischemic stroke or cardiovascular-related death did not occur in any patients; however, 3 deaths occurred: aspiration pneumonia (n=2) and cardiovascular implantable electronic device infection (n=1). There were 3 cases of major bleeding (1 case of cerebral hemorrhage, 2 cases of lower gastrointestinal bleeding). Follow-up imaging revealed no new device leakage or pericardial effusion, but 2 cases of DRT were noted.

Antithrombotic Therapy

Data from the 73 cases of successful LAAC were reviewed: 16 (21.9%) patients on regimen 1, 46 (63.0%) on regimen 2, and 11 (15.1%) on regimen 3. The prevalence of concomitant use of antiplatelet therapy at discharge was 100% (16/16 cases) in regimen 1, and 43.5% (20/46 cases) in regimen 2. All patients (100%) in regimen 1 completed the first imaging follow-up, 87.5% for the second imaging survey and 92.3% for the 1-year follow-up imaging. In regimen 2, all patients (100%) underwent the first and second (1 year later) imaging follow-up. In regimen 3, 75.0% of patients underwent the first follow-up imaging and 66.6% underwent the second imaging follow-up. In regimen 3, 2 of 11 (18.2%) patients received single antiplatelet therapy (SAPT) at discharge. The patients’ baseline characteristics are shown in Table 1, excluding the patient who did not receive the implant. Age (71±7 vs. 74±9 vs. 71±12 years, P=0.18) and sex (male: 88 vs. 67 vs. 82%, P=0.23) distributions were comparable among the groups. Thromboembolic risk (CHA₂DS₂-VASc score 4.6±1.0 vs. 4.5±1.3 vs. 4.2±1.2, P=0.60) and bleeding risk (HAS-BLED score 3.3±0.6 vs. 3.2±0.9 vs. 3.7±0.6, P=0.19) were also comparable. However, BARC type 3 bleeding history (19% vs. 41% vs. 72%, P=0.0198) significantly differed between groups. The history of BARC type 3 bleeding is shown in Figure 2 and summarized in the Supplementary Table. Intracranial bleeding was the most frequently observed bleeding event and gastrointestinal bleeding was also common. Bleeding events resulting in subcutaneous hematoma and/or epistaxis, causing a hemoglobin drop of 3 to <5 g/dL and necessitating transfusion, were classified as BARC type 3 bleeding, considering that the patients had hematologic diseases such as leukemia and EVANS syndrome. Only the regimen 3 group included patients undergoing hemodialysis (n=3); no patient had a history of BARC type 3 bleeding. The regimen 3 group also included 2 (18.2%) patients who ceased antiplatelet therapy: 1 patient received antiplatelet therapy for 10 days and the other received it only for 3 days because of uncontrollable bleeding. The proportion of patients with congestive heart failure (25% vs. 11% vs. 55%, P=0.0049) was higher in the regimen 3 group than in the other groups.

Table 1.

Baseline Clinical Characteristics

	Regimen 1 (n=16)	Regimen 2 (n=46)	Regimen 3 (n=11)	P value
Age (years)	71±7	74±9	71±12	0.18
Male (%)	14 (88)	31 (67)	9 (82)	0.23
Body mass index (kg/m2)	24±5	24±4	22±4	0.28
AF pattern
Paroxysmal (%)	8 (50)	17 (37)	6 (55)	0.45
Nonparoxysmal (%)	8 (50)	29 (63)	5 (45)
Prior AF ablation (%)	6 (38)	16 (35)	1 (9)	0.22
CHADS2 score	3.3±1.0	3.3±1.1	3.1±1.4	0.75
CHA2DS2-VASc score	4.6±1.0	4.5±1.3	4.2±1.2	0.60
HAS-BLED score	3.3±0.6	3.2±0.9	3.7±0.6	0.19
LVEF (%)	59±10	61±7	52±15	0.14
Risk factors
Congestive heart failure (%)	4 (25)	5 (11)	6 (55)	0.0049
Hypertension (%)	11 (68)	41 (89)	9 (82)	0.16
Diabetes mellitus (%)	9 (56)	14 (30)	7 (64)	0.05
Stroke/TIA/SE (%)	13 (81)	28 (61)	4 (36)	0.06
Vascular disease (%)	3 (19)	3 (7)	6 (27)	0.12
Abnormal renal function (%)	6 (40)	11 (24)	6 (55)	0.16
Abnormal liver function (%)	0 (0)	1 (2)	1 (9)	0.34
Labile INRs (%)	0 (0)	3 (7)	2 (18)	0.18
Drugs/alcohol (%)	9 (56)	8 (17)	3 (27)	0.0110
Hyperlipidemia (%)	7 (44)	16 (35)	7 (64)	0.21
Smoking (%)	11 (69)	23 (50)	9 (82)	0.10
Stage III–IV CKD (%)	8 (50)	23 (50)	6 (55)	0.96
Hemodialysis/Peritoneal dialysis (%)	0 (0)	0 (0)	3 (27)	<0.0001
History of cardioembolic stroke (%)	8 (50)	21 (46)	4 (36)	0.78
History of major bleeding (BARC type 3) (%)	3 (19)	19 (41)	8 (72)	0.0198

AF, atrial fibrillation; BARC, Bleeding Academic Research Consortium; CKD, chronic kidney disease; INR, international normalized ratio; LVEF, left ventricular ejection fraction; SE, systemic embolism; TIA, transient ischemic attack.

Figure 2.

History of Bleeding Academic Research Consortium type 3 bleeding.

Periprocedural characteristics are presented in Table 2. No major peri-device leakages (≥5 mm) were found in the 73 patients with successful implantation, and minor peri-device leakage (<5 mm) (6% vs. 4% vs. 0%, P=0.72) occurred at similar rates in all 3 groups. The grade of LAA spontaneous echo contrast (≥grade 3) (13% vs. 13% vs. 9%, P=0.94) was similar across groups. The postprocedural outcomes are presented in Table 3, including procedure-related complications, such as pericardial effusion/tamponade, access-related complications, contrast-related renal injuries, procedure-related complications, adverse events, such as DRT, and death. Three patients each in regimens 1 (18.8%) and 2 (6.5%) did not follow the treatment because of DRT or major bleeding events, and there was 1 case of severe hematuria. Those who had bleeding events were followed up and underwent CT examination 1 month after changing antithrombotic therapy. DRT (13% vs. 0% vs. 0%, P=0.0257) occurred with regimen 1 and all cases were detected in the DAPT period.

Table 2.

Periprocedural Characteristics

	Regimen 1 (n=16)	Regimen 2 (n=46)	Regimen 3 (n=11)	P value
LAA ostium maximal diameter measured by TEE during procedure (mm)	23±4	24±4	24±3	0.66
LAA depth maximal diameter measured by TEE during procedure (mm)	31±6	28±6	28±6	0.34
Implanted device WATCHMAN 2.5 (%)	14 (88)	19 (41)	5 (45)	0.0056
Implanted device size	29±3	29±4	30±3	0.99
21 mm (%)	0 (0)	2 (4)	0 (0)
24 mm (%)	2 (13)	6 (13)	0 (0)
27 mm (%)	5 (31)	12 (26)	5 (45)
30 mm (%)	3 (19)	5 (11)	2 (18)
31 mm (%)	1 (6)	8 (17)	2 (18)
33 mm (%)	4 (25)	5 (11)	1 (9)
35 mm (%)	1 (6)	8 (17)	1 (9)
Recapture	0.5±0.5	0.9±1.4	0.5±0.7	0.94
No. of devices per patient	1.2±0.4	1.2±0.4	1.3±0.5	0.53
Peri-device leakage
≥5 mm	None	None	None
<5 mm (%)	1 (6)	2 (4)	None	0.72
LAA spontaneous echo contrast (%)	2 (13)	6 (13)	1 (9)	0.94
Procedure time (min)	46±9	47±14	47±11	0.97
Fluoroscopy time (min)	9±4	9±4	9±3	0.87
Contrast media volume (mL)	77±29	70±23	57±30	0.22
Anticoagulant post procedure
Warfarin (%)	1 (6.3)	2 (4.3)	–	0.76
DOAC (%)	15 (93.8)	44 (95.7)	–	0.76

DOAC, direct oral anticoagulant; LAA, left atrial appendage; TEE, transesophageal echocardiography.

Table 3.

Postprocedural Outcomes

	Regimen 1 (n=16)	Regimen 2 (n=46)	Regimen 3 (n=11)	P value
Device-related outcomes
Major adverse events ≤7 days	None	None	None
Device dislodgement/embolization	None	None	None
Device-related thrombus (%)	2 (13)	None	None	0.0257
Clinical outcomes
Ischemic stroke	None	None	None
Major bleeding (%)	1 (6)	1 (2)	1 (9)	0.53
Pericardial effusion at 6 months	None	None	None
30-day mortality	None	None	None
All-cause mortality (%)	None	1 (2)	2 (18)	0.0360
Cardiovascular-related	None	None	None
Noncardiovascular-related (%)	None	1 (2)	2 (18)	0.0360
Follow-up period (days)	577±52	369±35	362±69	0.0135

In contrast, the rates of major bleeding events were comparable among the 3 groups; deaths from any (non-cardiovascular) cause (0% vs. 2% vs. 18%, P=0.0360) were more common in the regimen 3 group than in the other groups.

DRT

Two cases of DRT occurred in this study and in both the DRT was detected during ongoing DAPT. Figure 3 and Table 4 show the clinical course and data for the 2 DRT cases, respectively. One case of DRT occurred in a patient who was administered regimen 1. A 2.7-mm peri-device leakage was found 47 days after LAAC. This patient had received an anticoagulant drug for 6 months because of a history of 2 cardioembolic strokes with no history of bleeding. The patient and the primary doctor wanted to continue DOAC intake, but the patient was switched to DAPT 6 months after LAAC. Nine months later, a 15.5×20.8-mm DRT was detected during the ongoing DAPT. Thus, the antithrombotic therapy for this patient was changed to DOAC and SAPT. Three months later, 1 year after the procedure, we confirmed the disappearance of DRT through CT and changed the regimen to SAPT. Although this patient had a recurrence of DRT, there was a period of no antithrombotic therapy. The patient experienced thalamic hemorrhage 1 week after switching to SAPT, and it was necessary to halt the antithrombotic therapy. Two months later (14 months after LAAC), we performed follow-up CT and detected DRT recurrence. We added DOAC to the antithrombotic therapy regimen, and 3 months later, the DRT appeared reduced. An additional 3 months later, we confirmed the disappearance of DRT. We then modified the medication to SAPT, and 5 months later, the patient had had no recurrence.

Figure 3.

Details of 2 cases of device-related thrombus (DRT). ASA, acetylsalicylic acid; CT, computed tomography; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; SAPT, single antiplatelet therapy; TEE, transesophageal echocardiography.

Table 4.

Clinical Data of 2 Cases of Device-Related Thrombosis

	Case 1	Case 2
Demographics	66 years, male, persistent AF, CHA2DS2-VASc score: 5, HAS-BLED score: 4	83 years, female, persistent AF, CHA2DS2-VASc score: 6, HAS-BLED score: 3
Indication for LAAC	Prior stroke and HBR	Prior stroke under DOAC and HBR
Implantation device type and size	WATCHMAN 2.5, 24 mm	WATCHMAN 2.5, 27 mm
Antithrombotic therapy on detection of DRT	DAPT (clopidogrel 75 mg and aspirin 100 mg)	DAPT (clopidogrel 75 mg and aspirin 100 mg)
DRT detection date	9-month CT follow-up	7-month CT follow-up
Cardiac rhythm with DRT	AF	AF
DRT size	15.5×20.8 mm	15.1×20.6 mm
Peri-device leakage	2.7 mm	None
Embolic event	None	None
Duration to DRT resolution	3 months	3 months

AF, atrial fibrillation; CT, computed tomography; DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulant; DRT, device-related thrombus; HBR, high bleeding risk; LAAC, left atrial appendage closure.

In the second case, the patient had a history of cardioembolic stroke and DOAC intake, but no bleeding events were recorded for 45 days after the procedure. Both the patient and her primary doctor wanted her to continue with DOAC therapy for 98 days. A 15.1×20.6-mm DRT was detected during ongoing DAPT, 7 months after LAAC. We prescribed DOAC for 3 months. After confirming via CT that the thrombus had disappeared, anticoagulation therapy was discontinued and SAPT was introduced. Four months later (14 months after LAAC), follow-up CT confirmed that the patient was DRT-free (Figure 4).

Figure 4.

Computed tomography images of device-related thrombus in Case 1 (A) and Case 2 (B).

Discussion

This is the first report to focus on the antithrombotic regimens after LAAC device implantation in Japan. The early- and mid-term outcomes of the first 74 consecutive patients who underwent LAAC at our institution are presented. LAAC was successful in 73 (98.6%) patients, and 71 (95.9%) patients had no complications related to the procedure. Only 2 cases (2.7%) of DRT occurred in this cohort. These findings indicated that a modified regimen was not associated with a higher rate of complications or bleeding than the IFU-listed regimen.

Real-World Data on LAA Occlusion in Japan

The WATCHMAN device was introduced in the 2018 Japanese Circulation Society (JCS)/Japanese Heart Rhythm Society (JHRS) guidelines on non-pharmacotherapy for cardiac arrhythmias¹⁶ and has been used in Japan since September 2019. The procedural success rate was 98.6% (73/74 cases) at our institution, 98.2% (54/55 cases) at Kokura Memorial Hospital, and 100% (42/42 cases) in the SALUTE trial, compared with 95.6% (3,653/3,822 cases) in the USA after FDA approval.^11,12,17,18 Currently, no data support the use of LAAC instead of DOAC in general nonvalvular AF patients; hence, it remains a Class 2b recommendation even in the JCS/JHRS 2021 guideline focused update on non-pharmacotherapy of cardiac arrhythmias.³

Antithrombotic Therapy for Japanese Patients With AF

LAAC is widely used in Japan to prevent cardiogenic embolism in patients with AF, and several studies have reported its effectiveness as an alternative to OAC therapy.^11,12,17 However, the optimal type and duration of treatment for Japanese patients remain unclear. In Japan, HBR is an indication, and most patients treated with LAAC have HBR or had prior BARC type 3 bleeding.³ The use of a combination of anticoagulant and antiplatelet drugs and DAPT, which are powerful antithrombotic therapies, does not match real-world clinical practice in Japan. Several previous studies from around the world have suggested that individual adjustments are necessary; in fact, strict adherence to the complete FDA-approved postprocedural antithrombotic therapy is rare.⁶ As a new choice of postprocedural antithrombotic therapy, mainly in Europe and the USA, DAPT (or SAPT) is suggested after LAAC (e.g., the regimen in the ASAP trial¹⁹). Chinese expert consensus states that “patients who are unable to adhere to/tolerate long-term OAC (e.g., living alone, dementia, or disability) but may tolerate short-term (2–4 weeks) single anticoagulant or DAPT may be considered for LAAC.”²⁰ Additionally, the EHRA/EAPCI expert consensus statement in 2020 asserted that “AF patients who have absolute contraindications for long-term OAC may be considered for LAAC if a single antiaggregant can be administered for a minimum period (2–4 weeks).” A clear-cut definition of an absolute contraindication to OAC was not mentioned; however, it was recommended that LAAC should be performed for patients with an excessively high risk of major, life-threatening or disabling bleeding, rather than no treatment.²¹ Thus, we performed LAAC for patients who had to cease anticoagulant drugs due to bleeding risk and prescribed regimen 3 for them. On detection of DRT during the DAPT period, the use of apixaban (2.5 mg/12 h) or rivaroxaban (10 mg) with aspirin and a low-dose DOAC, such as apixaban (5 mg/12 h, 2.5 mg/12 h) alone, has also been recommended.^22,23 However, this regimen cannot be simply adapted to Japanese patients because previous research rarely included the WATCHMAN devices (WATCHMAN 2.5 and WATCHMAN FLX) (2%) available only in Japan, and DOAC constituted the usual treatment for Japanese patients. Antiplatelet therapy without OAC as an immediate therapy after LAAC with a WATCHMAN device is associated with an increased rate of DRT.⁸ DRT is a red thrombus caused by venous congestion; thus, antiplatelet therapies may be ineffective. In addition, by 90 days in dogs there is a complete endocardial lining of the former LAA ostium, suggesting that anticoagulant therapy for at least 90 days may be appropriate.²⁴

We have presented the outcomes of reduced-dose postprocedural antithrombotic therapy in Japanese patients. DRT, a problem associated with reduced doses of antithrombotic therapy, occurred in only 2 patients who received the IFU-listed regimen and in both cases, DRT occurred during the DAPT period. The overall rate of DRT was 2.7%, which is comparable to that reported in a meta-analysis (3.75%).²⁵ These results suggest that the risk of DRT may be higher during the DAPT period than at other times.²⁶

Antithrombotic Therapy After DRT

In this study, anticoagulation therapy was resumed on detection of DRT. In one of the cases, treatment was changed to SAPT and DOAC, and in the other, treatment was changed to only DOAC. After 3 months, TEE or CT examination confirmed that the thrombus had disappeared; anticoagulation therapy was discontinued and SAPT was introduced. No guidelines specify a definitive treatment for DRT. The most common treatment strategy is to restart warfarin (prothrombin time–international normalized ratio (PT-INR) 2.0–3.0) for 8–12 weeks in patients not taking anticoagulants at the time of DRT detection.²⁷ Patients already taking warfarin should be adjusted to PT-INR 2.5–3.5. If the bleeding risk is low, aspirin can be added. Similarly, a full dose of DOAC (edoxaban and apixaban; avoid dabigatran) can be restarted. If the thrombus is large (>15 mm) and mobile, treatment with a low-molecular-weight heparin may be considered. Surgical removal of the thrombus and LAA device may be required in the case of device thrombus, embolism from DRT, or anticoagulation therapy failure. In our opinion, similar outcomes may be achieved with post-DRT antithrombotic therapy that involves resuming OAC for 3 months and switching to SAPT after TEE shows the disappearance of DRT. If DRT is persistent, continuation of DOAC, switching to warfarin, or surgical resection should be considered.

The largest dataset on DRT is currently from a multicenter trial dedicated to the LAAO-DRT registry.²⁵ That study revealed 1 major (hypercoagulable state or iatrogenic pericardial effusion) and 2 minor (deep LAAC implant, chronic renal injury, or nonparoxysmal AF) factors that increased the risk of DRT 2.1-fold. In the present study, only 1 risk factor (nonparoxysmal AF) was observed in both DRT cases. This scoring precludes the assessment of DRT risk. Given that 43 (58.1%) patients had nonparoxysmal AF, it would have been difficult to change the postoperative treatment.

Study Limitations

This was a single-center observational study with a small sample, and hence may have been statistically underpowered. The adherence rate to the follow-up imaging protocol, which was intended to assess the feasibility and safety of a modified antithrombotic regimen, was low for patients on regimen 3; this raises concerns about the effectiveness and safety of the modified regimen. Further studies in the Japanese population are required to clarify the optimal post-LAAC antithrombotic therapy in this patient group.

Conclusions

This study presents findings on initial induction, postoperative management, and clinical outcomes of LAAC at a single institute. The postprocedural antithrombotic regimen was modified without major concerns.

Disclosures

This study did not receive any specific funding. Dr. Kondo received lecture fees from Daiichi-Sankyo, Bayer, Abbott Medical Japan, Biotronik Japan, and Boston Scientific, Japan Lifeline, and research funds from Daiichi-Sankyo. Dr. Kobayashi received lecture fees from Abbott Medical Japan, Bayer Japan, Bristol-Myers Squibb, Boehringer Ingelheim, and Daiichi-Sankyo, and scholarship funds from Takeda Pharmaceutical, Abbott Medical Japan, Terumo, Otsuka Pharmaceutical, Boehringer Ingelheim, Astellas, Daiichi-Sankyo, Win International, Japan Lifeline, and Nipro. Dr. Kobayashi is a member of Circulation Journal’s Editorial Team.

IRB Information

This study was approved by the Ethics Committee of Chiba University Graduate School of Medicine (approval no. 4013).

Data Availability

The data generated in this study will not be shared.

Supplementary Files

Please find supplementary file(s);

https://doi.org/10.1253/circj.CJ-22-0687

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