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Abstract
Introduction The prevalence of atrial fibrillation (AF) is increasing globally, and stroke prevention is the key to reduce the morbidity and mortality related to AF. Currently, direct oral anticoagulants (DOACs) are the primary options for stroke prevention, while it increases risk of bleeding. Left atrial appendage (LAA) is suspected as a vital source of cerebral emboli and may lead to ischaemic stroke, and thoracoscopic LAA clipping procedure provides an alternative option for stroke prevention in high-risk patients. However, high-quality evidence comparing LAA clipping to DOACs in terms of stroke prevention is lacking. This trial is designed to assess whether the efficacy of thoracoscopic LAA clipping is superior to DOACs for stroke prevention in AF patients at high risk of thrombosis (CHA2DS2-VASc≥2 in men and ≥3 in women)[CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female)”].
Methods and analysis This is a prospective, multicentre, open-labelled, randomised controlled study. This trial will randomly assign 290 patients with non-paroxysmal AF to thoracoscopic LAA clipping group or DOAC therapy group in a 1:1 randomisation. The primary endpoint is defined as a composite endpoint event consisting of stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events at 24 months after randomisation. The secondary endpoints consist of the components of the primary composite endpoint, surgery-related adverse events and minor bleeding events.
Ethics and dissemination The central ethics committee at Fuwai Hospital approved the trial entitled “Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation (LAA-CLIP trial)”. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.
Trial registration number NCT06021808.
- atrial fibrillation
- left atrial appendage clipping
- stroke
- bleeding
- direct oral anticoagulants
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Randomisation is stratified according to centre and balanced using randomly permuted blocks (four or six patients per block), and an interactive web-based response system will be used to preserve allocation concealment.
The primary endpoints include both ischaemic and bleeding events to evaluate left atrial appendage clipping versus direct oral anticoagulants in terms of stroke prevention.
The Questionnaire for Verifying Stroke-Free Status with high negative predictive value is used to screen the ischaemic events, and neurological imaging findings for participants with positive answers are required to reduce false positive.
It is not possible to blind surgeons and participants to the treatment arms, however, research staff and members of the clinical events committee are all blinded to the randomisation schemes.
Introduction
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia disease, and the incidence of AF increases markedly with age and approximately doubles with each decade.1–3 According to the previous study, the incidence of stroke was five times higher in patients with AF than those in the general population.4 Systemic oral anticoagulant is a well-established, guideline-recommended therapy for the prevention of ischaemic stroke in patients with non-valvular AF at high risk of embolism (CHA2DS2-VASc scores ≥2 in men and ≥3 in women), and current guidelines recommend that the direct oral anticoagulants (DOACs) be preferred (class I, level of evidence A).5 However, a significant proportion of patients with non-valvular AF have difficulties in long-term oral anticoagulant therapy, due to medication adherence and contraindications to oral anticoagulants.6 Also, several randomised controlled trials (RCTs) indicated that bleeding risk remained high with DOACs.7–9 Recently, alternative treatment strategies for stroke prevention in patients with non-valvular AF have been explored, such as left atrial appendage (LAA) occlusion or LAA closure.
It has been reported that LAA is suspected as a vital source of cerebral emboli and may lead to ischaemic stroke, removal or closure of LAA may be an alternative to oral anticoagulants.10 11 Various surgical or interventional approaches have been developed to close or occlude LAA to prevent stroke in AF patients, such as percutaneous LAA occlusion, suture ligation and surgical excision. However, these techniques suffer from incomplete LAA closure or the presence of residual blood flow, which can lead to thrombosis and stroke,12–14 and stand-alone surgical excision is less popular due to the invasive nature of the surgical procedure. Thoracoscopic LAA clipping, on the other hand, can block blood flow between LAA and left atrium, achieving isolation of LAA and preventing thrombi and strokes. A previous study has demonstrated a high 95% success rate of LAA clipping without operation-related complications, and freedom from stroke was 99.1% at a median follow-up of 20 months.15 Therefore, LAA clipping is an effective and durable method in stroke prevention. However, we currently lack high-quality RCTs to support the superiority of LAA clipping compared with DOACs in terms of stroke prevention. In this trial, we designed a multicentre prospective RCT to compare the efficacy of thoracoscopic LAA clipping and DOACs in patients with non-paroxysmal AF for stroke prevention (LAA-CLIP trial), which could provide an alternative strategy of stroke prevention for AF patients as a substitute for DOACs.
Methods and analysis
Study objective
The LAA-CLIP trial is designed to examine the hypothesis that thoracoscopic LAA clipping is superior to DOACs for stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events in AF patients at high risk of embolism (CHA2DS2-VASc≥2 in men and ≥3 in women).
Study design
LAA-CLIP is a multicentre, prospective, open-label, two-arm, parallel RCT designed to compare the efficacy of thoracoscopic LAA occlusion to DOAC therapy for prevention of thromboembolism and bleeding in non-paroxysmal AF (figure 1). The study is approved by ethics committees in Fuwai Hospital and has been registered at ClinicalTrials. gov, identifier NCT06021808. All participating sites accepted the central ethics approval or obtained approval by the local ethics committee. The LAA-CLIP trial was scheduled to begin recruitment in February 2024 and expected to complete recruitment by the end of January 2026. A 24-month follow-up will be conducted until the end of January 2028.
Study design of LAA-CLIP trial. AF, atrial fibrillation; DOAC, direct oral anticoagulant; LAA, left atrial appendage.LAA-CLIP stands for the trial entitled “Epicardial left atrial appendage clipping versus direct oral anticoagulant to reduce stroke risk in non-paroxysmal atrial fibrillation”. CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female).
Participant screening and enrolment
This study will screen potential participants in outpatient clinics and determine their eligibility based on the medical history and examination results. In brief, detailed medical history along with blood count, coagulation function, liver and kidney function, echocardiography, enhanced left atrial CT, 24-hour Holter and every previous 12-lead ECG will be collected to determine the eligibility. On confirmation of eligibility, all participants will receive complete verbal and written information about the study. Participants are encouraged to ask any questions about the trial, and they have sufficient time to consider or discuss with family whether to participate in this study. A written consent is mandatory prior to enrolment and randomisation.
This trial will recruit participants from nine academic cardiac centres all over Chinese mainland. Participants aged ≥18 years, with non-paroxysmal AF (CHA2DS2-VASc≥2 in men and ≥3 in women) that are not undergoing ablation, will be eligible for enrolment. The exclusion criteria include willingness to electrical cardioversion or ablation, other heart diseases with surgical indications, recent ischaemic or bleeding events, contraindications to anticoagulation, other diseases requiring oral anticoagulants, and requiring dual antiplatelet drug therapy, history of previous cardiac and left lung surgery (see box 1 for details). Specially, patients with pre-existing LAA thrombus determined by either enhanced left atrial CT or echocardiography will be excluded in this trial. Prior to the enrolment, the investigators shall provide the potential participants or their legal representative with a complete, comprehensive, easily understandable and ethics committee-approved informed consent. Investigators will introduce the trial objective, design, interventions and potential risks and benefits in detail to the participants.
The inclusion and exclusion criteria for the study
Inclusion criteria
Age ≥18 years.
Persistent or long-standing persistent atrial fibrillation documented by medical history or ECG.
CHA2DS2-VASc≥2 in men and ≥3 in women.[ CHA2DS2-VASc stands for "congestive heart failure, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category (female)."].
Agree to perform thoracoscopic left atrial appendage occlusion procedure.
Exclusion criteria
Willingness to electrical cardioversion or ablation.
Other heart diseases requiring surgical operations.
Ischaemic stroke and other cardiac embolic events within 30 days.
Major clinical bleeding event within 30 days.
Contraindications to anticoagulation.
Intracardiac thrombus.
Left ventricular ejection fraction <30%.
Active systemic infection or infective endocarditis or pericarditis.
Severe liver disease (acute clinical hepatitis, chronic active hepatitis, cirrhosis) or alanine transaminase/aspartate transaminase greater than three times the upper limit of normal value.
Severe renal insufficiency (eGFR≤30 mL/min).[eGFR, estimated glomerular filtration rate. An estimated number based on blood creatinine test, age, body size, and gender that measures level of kidney function].
Other diseases requiring oral anticoagulants.
Active aortic plaque.
Acute coronary syndrome within 3 months.
Symptomatic carotid artery stenosis.
Patients requiring dual antiplatelet drug therapy.
Previous cardiac and left lung surgery.
Severe left pleural and pericardial adhesions.
Pregnant or breastfeeding patients.
Metal allergies.
Terminal illness with a life expectancy of less than 2 years.
Participation in other clinical studies at the time of enrolment.
Refuse to participate in this study.
Randomisation
Eligible participants are 1:1 randomly assigned to LAA clipping group or DOAC therapy group. An interactive web-based response system will be used to preserve allocation concealment. Randomisation is stratified according to centre and balanced using randomly permuted blocks (four or six patients per block). Surgeons and participants are aware of randomisation results. However, research staff and members of the clinical events committee (CEC) are all blinded to the randomisation schemes.
Treatment arms
DOAC group
Participants randomised to DOAC therapy will begin long-term oral administration of rivaroxaban immediately after randomisation. Specifically, for participants with serum creatinine clearance ≥50 mL/min, oral rivaroxaban 20 mg daily will be administered, whereas for participants with serum creatinine clearance between 30 and 49 mL/min, oral rivaroxaban 15 mg daily will be administered.
LAA clipping group
In this arm, participants performed thoracoscopic LAA clipping procedure. The procedure is performed on the left side. After anaesthesia, a 10 mm scope is placed through the third intercostal space across the left anterior axillary line via a 1.5 cm incision. Next, the other two working ports will be established in the fourth intercostal space across the left midaxillary line and the second intercostal space across the left midclavicular line. Then, surgeons measure the length of the base of the LAA, an appropriately sized LAA clip (E-Clip, Med-Zenith, China) is then inserted with the aid of a thoracoscope and placed parallel to the base of the LAA.15–20 After the procedure, rivaroxaban will be administered for 3 months, and left atrial CT will be conducted 3 months postoperatively to assess the success of LAA clipping procedure. Successful LAA clipping is defined as a 3-month postoperative left atrial CT suggesting no blood flow between LAA and left atrium, and the LAA stump less than 1 cm. DOAC therapy is continued if LAA clipping is unsuccessful, and the same DOAC therapy as the DOAC arm during the follow-up period. However, this occurrence is defined as a protocol deviation, and these participants will not cross over to DOAC arm in the subsequent study. If LAA clip is successfully inserted, the participants will discontinue anticoagulant drug and replace it with long-term oral aspirin (100 mg, once a day).
Study end points
Primary endpoints: The primary endpoint of this study is defined as a composite endpoint event consisting of stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events occurring within 24 months of randomisation.
Secondary endpoints: The secondary endpoints consist of the following three parts during the 24-month follow-up: (1) components of the primary composite endpoint, that is, stroke, systemic embolism, all-cause mortality, major bleeding events and clinically relevant non-major bleeding events; (2) surgery-related adverse events, including in-hospital death or stroke and postoperative reintervention due to haemorrhage or pneumothorax and (3) minor bleeding events.
Study outcome definitions
All adverse events will be documented throughout the study, irrespective of treatment allocation. CEC is responsible for the determination of endpoint events during the follow-up.
Stroke is defined as an acute onset of focal or global neurological dysfunction due to cerebral, spinal cord or retinal vascular injury from haemorrhage or infarction. Symptoms or signs must last ≥24 hours, or symptoms/signs may last less than 24 hours if demonstrated by CT and/or MRI of the brain or autopsy.
Systemic embolism is defined as acute vascular insufficiency or occlusion of the extremities or any non-central nervous system organ supported by clinical, imaging, surgical or autopsy evidence of arterial occlusion with no other possible mechanism such as trauma, atherosclerosis or device injury.
Major bleeding is identified according to the International Society on Thrombosis and Haemostasis (ISTH),21 which is defined as (1) fatal bleeding (bleeding that directly results in death) and/or (2) symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome and/or (3) bleeding causing a fall in haemoglobin level of 2.0 g/dL or more, or leading to transfusion of two or more units of whole blood or red blood cells.
Clinically relevant non-major bleeding is defined as bleeding that does not meet the ISTH criteria for a major bleeding event but that requires hospitalisation or a change in antithrombotic therapy strategy or invasive management.22
Minor bleeding is defined as bleeding that do not meet the ISTH criteria for major bleeding events and the clinically relevant non-major bleeding events, and that do not require the subjects to seek additional assistance from medical personnel, such as skin ecchymosis, gingival bleeding, epistaxis and other minor bleeding.
Data collection and follow-up
All data in this study are processed through a set of specially developed web-based data entry systems on the Chinese Cardiac Surgery Registry website (http://ccsr.cvs-china.com). The baseline data and follow-up questionnaires of subjects from collaborating institutions will be recorded as electronic data and uploaded to the central server of Fuwai Hospital. The set of web-based data entry systems is used for data collection, follow-up and management. Authorised researchers will require a separate username and password for each access to the data server, and the project leader will limit the researcher’s ability to perform functions and access data based on the researcher’s role in the study. The dataset for this study includes the following four modules: (1) subject screening, (2) informed consent and randomisation; (3) baseline information and (4) 6-month, 12-month, 18-month and 24-month follow-up data.
The baseline characteristics include demographic information, comorbidities, oral medications, preoperative examination (echocardiography, coagulation function, etc) postoperative complications and discharge data. Collaborating institutions may directly import the baseline information into the dataset. The baseline information of patients in LAA clipping group should be completed within 14 days after discharge, and the baseline data of patients in DOAC group will be completed immediately after randomisation.
For the follow-up data management, a professional team blinded to the group allocation is responsible for telephone video interview follow-up with participants using social media. All video interviews are recorded and stored in the server. Follow-up data were collected at 6, 12, 18 and 24 months postoperatively in both the LAA clipping group and DOAC therapy group. Each follow-up visit includes stroke, systemic embolism, survival status, bleeding events of any degree at any site. A questionnaire including survival status, stroke, peripheral thromboembolic events, bleeding events and medication administration will be used to assess the status of participants. All the answers to the relevant questions will be uploaded into the online dataset. Specifically, stroke status is assessed according to the Questionnaire for Verifying Stroke-Free Status (QVSFS) questionnaire (box 2). To avoid false positives, participants are required to provide imaging information such as CT or MRI of the head if participants have at least one positive response in the questionnaire. If the patients fail to provide the information, they will be considered as lost to follow-up.
Questionnaire for verifying stroke-free status (QVSFS)
QVSFS questionnaire
Were you ever told by a physician that you had a stroke?
Were you ever told by a physician that you had a TIA, ministroke or transient ischaemic attack?
Have you ever had sudden painless weakness on one side of your body?
Have you ever had sudden numbness or a dead feeling on one side of your body?
Have you ever had sudden painless loss of vision in one or both eyes?
Have you ever had suddenly lost one half of your vision?
Have you ever suddenly lost the ability to understand what people are saying?
Have you ever suddenly lost the ability to express yourself verbally or in writing?
Statistical analysis plan
Sample size calculation: The calculation of the sample size is based on the primary endpoint according to previously published data. For LAA clipping group, based on previous studies,23–25 the anticipated incidence of the primary composite endpoint event during the 24-month follow-up is 7%. As for DOAC group, the anticipated incidence of the primary composite endpoint is 19% based on the available researches.7–9 26 Sample size calculations assume 80% power and a 5% (two-sided) significance level. Therefore, a sample size of 123 participants (per group) is needed to test the superiority hypothesis of the study. To secure adequate power of the trial and account for an estimated 15% withdraw rate, 290 participants are required to be randomly assigned into two groups in a 1:1 allocation (145 participants per group).
Statistical analysis: All primary data analyses will be based on the intention-to-treat principles, and the secondary endpoints will be analysed only as exploratory. In addition, a per-protocol and as-treated analysis are also performed to assess the efficacy of this trial. The categorical variables will be described as frequencies with percentages, and the continuous variables will be described as means with SD or medians with IQRs depending on whether they are normally distributed or not. The baseline participant characteristics and endpoints between DOAC group and LAA clipping group are compared by χ2 tests for categorical variables and Student’s t-tests for continuous variables. If the data distribution is not normal, appropriate transformation and/or non-parametric equivalent tests (eg, Mann-Whitney test) will be used. All statistical tests are two tailed with a significance level of 0.05.
Clinical event committee
The investigator is responsible for ensuring the accuracy, integrity and accessibility of the data reported in the web-based dataset. Patients will be inquired about their symptoms and signs in detail during the follow-up, and medical records are required to provide if the patients seek medical treatment during the follow-up period. An independent CEC will adjudicate all clinical outcomes in accordance with the study’s prespecified endpoint definitions and in accordance with the CEC charter, which comprises experienced experts in the field blinded to the randomisation schemes.
Patient and public involvement
The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents. Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Study design considerations
To our knowledge, this study first compares LAA clipping to DOACs in terms of stroke prevention and bleeding risk, which could provide an alternative therapy for AF patients.
AF is the most prevalent arrhythmic disease with a prevalence of 1%–2% in the general population and increasing rapidly worldwide.27–29 AF is characterised by irregular and abnormally fast contractions of the atrial cardiomyocytes, resulting in several symptoms and complications. The irregular atrial contraction leads to haemodynamic changes, which in turn causes a significantly higher risk of thrombosis. Comparing to sinus rhythm, AF is associated with a fivefold higher of stroke incidence.30–32 Therefore, stroke prevention is a cornerstone to reduce morbidity and mortality related to AF. Current guidelines recommend the use of DOACs for stroke prevention (class I, level of evidence A).5 However, DOAC therapy can be compromised due to contraindications to anticoagulation or high risk of bleeding events in some patients. For instance, DOACs are contraindicated in patients with severe liver impairment given that all of the DOACs are hepatically metabolised to some extent.33 Also, plasma concentration of rivaroxaban is observed inversely correlated with a decrease in renal function, and rivaroxaban is contraindicated for use in patients with severe renal insufficient. Furthermore, age-related contraindications to medication are also present in the DOACs.34 It has been reported that terminal half-life of rivaroxaban is longer in elderly than in younger individuals.35 36 In ROCKET-AF trial, major bleeding and clinically relevant non-major bleeding occurred in 14.9% of the patients receiving rivaroxaban per year.7 Previous studies estimated that 14%–40% AF patients at risk of stroke were contraindicated to long-term oral anticoagulation, especially elderly patients.37–39 Therefore, the exploration of alternative treatments for DOACs in stroke prevention is essential for these patients.
The current guideline suggests that percutaneous LAA occlusion should be considered in patients with contraindications to long-term oral anticoagulation (class IIa, level of evidence B).3 Two non-inferiority RCTs, PROTECT-AF and PREVAIL, compared the efficacy of the Watchman LAA closure with that of oral warfarin for stroke prevention.40 Both of the trials suggested that LAA occlusion was non-inferior to DOACs on the composite endpoint event. Recently, next-generation Watchman FLX device also demonstrated favourable safety and efficacy outcomes for stroke prevention and improved certain limitations observed with the first-generation device, such as perforation risk and residual peridevice leak.41 Percutaneous LAA occlusion has been commonly used for stroke prevention, and the successful closure rate of percutaneous transcatheter LAA occlusion devices ranged from 91% to 98.5%.42–46 However, these endocardial devices such as Watchman device, which is the most widely used in LAA occlusion, are directly in contact with bloodstream, increasing the risk of ischaemic stroke due to the higher incidence of residual shunts and device embolisation.46 47 Therefore, percutaneous devices require temporary anticoagulation after implantation, after endothelialisation, the anticoagulation therapy is typically discontinued or at least switched to single antiplatelet therapy. If the occlusion is unsuccessful, continued DOAC therapy is necessary.30 48 For this reason, LAA occlusion is a less attractive option for patients with anticoagulation contraindications.49 On the other hand, LAA clip is released outside the cardiac chamber without direct contact with blood flow, which significantly reduces the risk of thrombosis. Furthermore, LAA clip is not limited by the abnormal morphologies of the LAA, while LAA occlusion device do not sit as well within LAAs under these circumstances. The LAA clip system is easy to perform and allows adjusting position of the clip as needed. During the surgery, transoesophageal echocardiography will be used to confirm the position of the clip and the absence of residual flow before it is officially released, which also reduces the occurrence of residual flow compared with LAA occlusion.41
Compared with open-chest LAA closure, thoracoscopic LAA clipping provides an alternative, less invasive and safer approach to LAA management in AF patients. Studies on LAA clipping have demonstrated a high rate of LAA closure, absence of clip-related complications and a favourable stroke prevention effect.15 20 Although LAA clipping has demonstrated an excellent occlusion of LAA blood flow, there are no large-scale, high-quality studies investigating the prevention of long-term stroke. In particular, no comparison studies between LAA-clipping and DOAC therapy are as yet available. This investigator-initiated study hypothesises that LAA clipping is superior to DOACs in prevention of stroke among non-paroxysmal AF patients. This study takes the first step to explore the efficacy of LAA clipping for stroke prevention in AF patients. If the hypothesis is supported by the result of LAA-CLIP trial, it provides high-quality clinical evidence for the use of the LAA clip for stroke prevention in AF patients.
We use the QVSFS questionnaire to observe the occurrence of stroke in this trial, which is also widely used in the recent studies on stoke prevention of AF patients.15 50 The structured questionnaire consists of eight questions, and subjects are defined as QVSFS negative only if responses to all eight questions are negative. According to the previous researches, QVSFS questionnaire has a negative predictive value of 0.96 and a positive predictive value (PPV) of 0.71 in prediction of stroke.51 Importantly, further studies have confirmed the questionnaire’s ability to efficiently and accurately identify stroke-free patients in a population with a much higher prevalence of stroke and more chronic conditions than the original study.52 Therefore, this questionnaire could identify the stroke-free patients even the majority of the participants is long-standing persistent AF patients at high risk of stroke. Despite of its relatively low PPV results in a lower accuracy to identify subjects with stroke and/or transient ischaemic attack, the QVSFS questionnaire is still viable as a screening tool. Moreover, participants with at least one positive response are required to provide neurologic imaging findings such as cranial CT or MRI to reduce false positive.
In this study, the primary outcomes also include clinically relevant non-major bleeding events. Bleeding Academic Research Consortium (BARC) synthesised data from previous studies and proposed a standard bleeding definition for cardiovascular clinical studies.53 The definition of clinically relevant non-major bleeding events is quite similar to that of type 2 bleeding in BARC criteria, requiring medical intervention, hospitalisation or prompting evaluation. Therefore, several high-quality clinical trials have also used it as an endpoint event.7 9 54 We further take the clinically significant bleeding events as primary endpoints, which will clarify whether LAA clipping has a superior safety profile in terms of bleeding events compared with DOACs. On the other hand, both bleeding and ischaemic events are defined as primary endpoints in our study. Previous studies of LAA occlusion also included both of bleeding and ischaemic events as primary endpoints and concluded non-inferiority.46 55 However, LAA occlusion significantly increased the risk of device-related embolisation. Different from previous studies, this trial aims to investigate LAA clipping versus DOAC therapy for stroke prevention in AF patients with a superiority design. Also, since the LAA clip does not enter the heart chambers and is not in direct contact with the bloodstream, it might significantly reduce the risk of thrombosis, and thus the incidence of stroke and systemic embolisation.15 20 Therefore, this study could fill the research gap on the efficacy of LAA clipping versus DOAC therapy in stroke prevention in AF patients.
In conclusion, LAA-CLIP trial is the first study to investigate whether thoracoscopic LAA clipping is superior to DOAC therapy in stoke prevention among non-paroxysmal AF patients. The results of this study may provide a safer and more effective treatment option for the prevention of stroke and embolism in patients with AF.
Ethics and dissemination
The current study protocol has been reviewed and approved by the central ethics committee at Fuwai Hospital (approval number: 2023-2059). All the enrolled participants are required to signature a written informed consent prior any study-specific assessments. The results of this study will be disseminated through publications in peer-reviewed journals and conference presentations.
Ethics statements
Patient consent for publication
References
Footnotes
CY, HL and CL contributed equally.
Contributors CY and CL: conceptualisation, methodology, writing–original draft. HL: conceptualisation, methodology and writing–review and editing. WY: methodology. SC: software and formal analysis. YZ: methodology and resources. ZZ: supervision, project administration, funding acquisition.
Funding The LAA-CLIP trial is supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2021-I2M-1-063) and the State Sponsored Postdoctoral Researcher Programme (GZC20230304).
Disclaimer The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.