Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation.

Background Transcatheter left atrial appendage closure (LAAC) with the WATCHMAN device has emerged as an alternative treatment option to oral anticoagulants. The WATCHMAN device was introduced in Japan in 2019, followed by the newer WATCHMAN FLX device in 2021. However, few studies have investigated sex differences in the outcomes of the LAAC procedure. Objective This study aimed to evaluate sex differences in LAAC procedures in Japan. To adjust for confounding factors, we employed two innovative matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). Methods The TERMINATOR (Transcatheter Modification of Left Atrial Appendage by Obliteration with Device) registry is a multicenter, real-world registry involving 23 institutions in Japan. This study enrolled 1,817 patients with atrial fibrillation who underwent LAAC at these institutions between September 2019 and September 2023. The primary efficacy endpoint was a composite of ischemic stroke, transient ischemic attack, or systemic embolism at 12 months. The primary safety endpoint was a composite of hemorrhagic stroke or anemia requiring transfusion at 12 months. The secondary endpoint was all-cause mortality through 12 months. A retrospective analysis was performed to compare clinical outcomes following LAAC, using propensity score matching (PSM) at a 1:1 ratio and IPTW to minimize potential bias. Results Of the 1,171 patients analyzed, 332 (28.4%) were women. Compared with men, women were older (78.1 ± 7.7 years vs. 74.86 ± 8.1 years; P < 0.001) and more likely to have paroxysmal atrial fibrillation (45.2% vs. 36.6%; P = 0.007). The CHA2DS2-VA and HAS-BLED scores were comparable between the sexes (4.4 ± 1.3 vs. 4.5 ± 1.4; P = 0.751 and 3.3 ± 0.8 vs. 3.3 ± 0.9; P = 1.000, respectively). After PSM, 330 men and 330 women were selected for the final analysis. As shown in the Kaplan–Meier analysis (Figure), no statistical differences were observed between the sexes in the primary efficacy and safety endpoints or the secondary endpoint. The IPTW method produced similar results. Conclusion In patients with atrial fibrillation undergoing LAAC, women demonstrated similar safety and efficacy outcomes compared with men.

BackgroundDespite guideline recommendations, evidence for the use of non–vitamin K antagonist oral anticoagulant (NOAC) monotherapy in patients with atrial fibrillation after implantation of a drug-eluting stent remains limited.MethodsIn this multicenter, randomized, open-label, noninferiority trial in South Korea, we assigned patients with atrial fibrillation who had undergone the implantation of a drug-eluting stent at least 1 year earlier in a 1:1 ratio to receive NOAC monotherapy or combination therapy (NOAC plus clopidogrel). The primary end point was net adverse clinical events, a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding at 12 months. The noninferiority margin was 3.0 percentage points.ResultsA total of 960 patients underwent randomization: 482 patients to receive monotherapy and 478 to receive combination therapy. The mean age of the patients was 71.1 years, and 21.4% were women. At 12 months, a primary end-point event had occurred in 46 patients (Kaplan–Meier estimate, 9.6%) in the monotherapy group and in 82 patients (Kaplan–Meier estimate, 17.2%) in the combination-therapy group, for an absolute difference of –7.6 percentage points (95.2% confidence interval [CI], −11.9 to −3.3; P<0.001 for noninferiority) and a hazard ratio of 0.54 (95.2% CI, 0.37 to 0.77; P<0.001 for superiority). Major bleeding or clinically relevant nonmajor bleeding occurred in 25 patients (5.2%) in the monotherapy group and in 63 patients (13.2%) in the combination-therapy group (hazard ratio, 0.38; 95% CI, 0.24 to 0.60).ConclusionsAmong patients with atrial fibrillation who had undergone implantation of a drug-eluting stent at least 1 year earlier, NOAC monotherapy was noninferior to combination therapy for net adverse clinical events. (Funded by Cardiovascular Research Center and Samjin Pharmaceutical; ADAPT AF-DES ClinicalTrials.gov number, NCT04250116.)

Dabigatran etexilate (Pradaxa®) is approved in the EU for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. In patients with NVAF in the phaseIII RE-LY trial, dabigatran etexilate dosages of 110 and 150mg twice daily were noninferior to warfarin with regard to the risk of stroke or systemic embolism (primary efficacy endpoint). The higher dosage was associated with a significantly lower risk of stroke or systemic embolism than warfarin, with no significant between-group difference in the risk of major bleeding (primary safety endpoint). Both dosages of dabigatran etexilate were associated with significantly lower rates of haemorrhagic stroke, intracranial bleeding and life-threatening major bleeding than warfarin. Dabigatran etexilate was also effective and generally well tolerated across various patient subgroups. The efficacy and tolerability of dabigatran etexilate was maintained for up to 6.7years in the RELY-ABLE extension study. Routine anticoagulation monitoring is not required in patients receiving dabigatran etexilate, and it is currently the only non-vitaminK antagonist oral anticoagulant (NOAC) with a specific reversal agent available. Although direct comparisons with other NOACs would be beneficial, dabigatran etexilate is a useful option for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Catheter ablation for atrial fibrillation (AF) is associated with a transitory increase in the risk of both thromboembolic and bleeding events. Evidence on the use of nonvitamin K antagonist oral anticoagulants (NOACs) in patients undergoing AF ablation mostly comes from small observational studies, underpowered to detect differences in clinical outcomes between NOACs and vitamin K antagonists (VKAs) treated patients. This updated meta-analysis aimed to determine the safety and efficacy of periprocedural anticoagulation with NOACs compared with VKAs in AF patients undergoing catheter ablation. We searched MEDLINE, Cochrane library, and web sources for randomized and observational studies comparing periprocedural treatment with NOACs and VKAs in patients undergoing AF ablation. The primary safety endpoint was major bleeding events, and the primary efficacy endpoint was thromboembolic events (a composite of systemic thromboembolism, transient ischemic attack, and stroke). A total of 29 studies with 12644 patients were included in the meta-analysis. Overall, patients on NOACs had a significantly lower risk of major bleeding compared to VKAs either in observational studies (Peto OR 0.68; 95% CI: 0.48-0.95; P=0.022; I2 =20%) or in RCTs (Peto OR 0.30; 95% CI: 0.14-0.62; P=0.001; I2 =28%). Uninterrupted NOACs reduced the risk of major bleeding when compared to uninterrupted VKAs (Peto OR 0.66; 95% CI: 0.45-0.96; P=0.028; I2 =1%), similarly, interrupted NOACs lowered the risk of major bleeding compared to interrupted VKAs (Peto OR 0.29; 95% CI: 0.13-0.66; P=0.003; I2 =0%; Pinteraction =0.076). The rate of thromboembolic complications was very low and did not significantly differ between the study groups either in observational studies (Peto OR 0.91; 95% CI: 0.49-1.67; P=0.755; I2 =0%) or in RCTs (Peto OR 0.14; 95% CI: 0.01-1.30; P=0.083; I2 =0%). Use of NOACs compared to VKAs significantly reduced the risk of bleeding in patients with AF ablation. Similarly, the risk of bleeding was lower with uninterrupted NOACs than with uninterrupted VKAs, and with interrupted NOACs than with interrupted VKAs. The rate of thromboembolic complications was extremely low in both study groups without any differences.

This observational study aimed to investigate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with malignancy. A total of 76 patients (mean age: 73.2 ± 8.9; 28 females) with AF and malignancy treated with NOAC were included in the analysis. The mean CHA2DS2-VASc and HAS-BLED scores were 3.2 ± 1.2 and 2.2 ± 0.9, respectively. The study population was taking dabigatran 150 mg (25%) twice daily (BID), apixaban 5 mg BID (25%), dabigatran 110 mg BID (24%), rivaroxaban 20 mg (18%) once a day (OD), rivaroxaban 15 mg OD (5%), or apixaban 2.5 mg OD (3%). NOAC therapy began, on average, 248 ± 238 days before malignancy diagnosis for an average duration of 1,000 ± 289 days. Stroke, transient ischemic attack, major and minor bleeding events, other adverse effects, and major cardiovascular complications during the follow-up period were collected. In our study population, no patients experienced thromboembolic events during therapy with any NOAC. We recorded a low global incidence of major bleeding (3.9%) with a mean annual incidence of 1.4%. No hemorrhagic stroke or subarachnoid hemorrhage was observed. Only nine patients (11.8%) experienced minor bleeding. According to our data, anticoagulation therapy with NOACs seems to be an effective and safe treatment strategy for nonvalvular AF patients with malignancy.

ObjectiveCurrent guidelines endorse the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). However, little is known about their safety and efficacy in valvular heart...

Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. Purpose We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes in real-world clinical practice. Methods We evaluated 53,649 AF patients treated with a NOAC using Korean National Health Insurance Service database during the period from January 2013 to December 2016. NOAC doses were classified as either underdosed or overdosed, consistent with U.S. Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Results Overall, 16,757 NOAC-treated patients (31.2%) were underdosed, 4,492 were overdosed (8.4%), and 32,400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (71±8 and 75±7 years of age vs. 70±9 years of age, respectively; p&lt;0.001), more likely female (39% and 53% vs. 38%, respectively; p&lt;0.001), and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 vs. 4.5±1.8, respectively; p&lt;0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 vs. 4.03 events/100 patient-years, p&lt;0.001), major bleeding (4.77 vs. 2.94 events/100 patient-years, p&lt;0.001), and all-cause mortality (5.43 vs. 3.05 events/100 patient-years, p&lt;0.001) compared with label-adherent use. Figure 1 Conclusion In routine clinical practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with increased risk for stroke or systemic embolism, major bleeding, and all-cause mortality in Asian patient with AF.

Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking. To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF. A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025. The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423). The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes. Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]). Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy. ClinicalTrials.gov Identifier: NCT04432220.

Findings of prior studies about the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients (≥80 years of age) with atrial fibrillation (AF) are controversial. So we performed a meta-analysis to evaluate the efficacy and safety of NOACs versus vitamin K antagonists (VKAs) in patients (≥80 years of age) with AF. A systematic review of PubMed, Cochrane, Embase, Web of Science and Chinese BioMedical databases was conducted until 1 October 2022. Studies reporting the effects and safety of NOACs versus warfarin in patients (≥80 years of age) with AF were included. Two authors independently performed study selection and data extraction. Discrepancies were resolved by consensus or through an independent third reviewer. Data were synthesised according to the Preferred Reporting Items for Systematic Reviews guidelines. We identified 15 studies providing data of 70 446 participants (≥80 years of age) suffering from AF. According to the meta-analysis (odds ratio (OR) (95% confidence interval, CI)), NOACs conferred better efficacy profile than VKAs in stroke and systemic embolism (0.8 (0.73-0.88)) and all-cause mortality (0.61 (0.57-0.65)). Otherwise, NOACs conferred a better safety profile than VKAs in major bleeding (0.76 (0.70-0.83)) and intracranial haemorrhage (ICH; 0.57 (0.47-0.68)). In conclusion, for patients (≥80 years of age) with AF, the risks of stroke and systemic embolism, all-cause mortality, were lower in NOACs compared to warfarin. The risks of major bleeding and ICH were also lower in NOACs compared to warfarin. NOACs showed better efficacy and safety than warfarin.

Background and Purpose- Several randomized trials and real-world studies have reported the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in Asian patients with atrial fibrillation; and therefore, this meta-analysis was aimed to compare the effects of NOACs with warfarin for atrial fibrillation stroke prevention in Asians. Methods- The PubMed and Embase databases were searched from January 2009 to February 2019 for studies on comparisons of NOACs versus warfarin in Asians. Risk ratios (RRs) with 95% CIs were pooled using a random-effects model. Results- Five NOAC trials and 21 observational cohorts were included. For the NOAC trials, compared with warfarin, NOACs was associated with reduced risks of stroke or systemic embolism (RR, 0.73; 95% CI, 0.59-0.90), all-cause death (RR, 0.83; 95% CI, 0.73-0.95), major bleeding (RR, 0.59; 95% CI, 0.48-0.72), and intracranial bleeding (RR, 0.36; 95% CI, 0.26-0.49). For the real-world data, compared with warfarin, NOACs was associated with decreased rates of stroke or systemic embolism (RR, 0.75; 95% CI, 0.68-0.82), ischemic stroke (RR, 0.70; 95% CI, 0.59-0.83), myocardial infarction (RR, 0.74; 95% CI, 0.58-0.93), all-cause death (RR, 0.67; 95% CI, 0.59-0.77), major bleeding (RR, 0.63; 95% CI, 0.55-0.73), intracranial bleeding (RR, 0.50; 95% CI, 0.43-0.59), and gastrointestinal bleeding (RR, 0.65; 95% CI, 0.51-0.84). The results did not change in the subgroup analyses based on the type and dose of NOACs. Conclusions- Based on published NOAC trials and real-world studies, the use of NOACs is noninferior to warfarin in Asians with atrial fibrillation irrespective of the NOAC type and dose.

AimsLittle is known about the effects of mental health conditions (MHCs) on the utilization of oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients. We aimed to assess whether MHCs affect initiation of OAC therapy among AF patients with special focus on non-vitamin K antagonist oral anticoagulants (NOACs).Methods and resultsThe Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry included all 239 222 patients diagnosed with incident AF during 2007–18 in Finland identified from national registries covering primary to tertiary care and drug purchases. Patients with previous depression, bipolar disorder, anxiety disorder, or schizophrenia diagnosis or a fulfilled psychiatric medication prescription within the year preceding the AF diagnosis were classified to have any MHC. The main outcome was OAC initiation, defined as first fulfilled OAC prescription after AF diagnosis. The patients’ mean age was 72.7 years and 49.8% were female. The prevalence of any MHC was 19.9%. A lower proportion of patients with any MHC compared with those without MHCs were initiated on OAC therapy (64.9% vs. 73.3%, P < 0.001). Any MHC was associated with lower incidence of OAC initiation [adjusted subdistribution hazard ratio (aSHR) 0.867; 95% confidence interval (CI) 0.856–0.880], as were depression (aSHR 0.868; 95% CI 0.856–0.880), bipolar disorder (aSHR 0.838; 95% CI 0.824–0.852), anxiety disorder (aSHR 0.840; 95% CI 0.827–0.854), and schizophrenia (aSHR 0.838; 95% CI 0.824–0.851), during the entire follow-up. Any MHC remained associated with impaired incidence of OAC initiation also in the NOAC era during 2015–18 (aSHR 0.821; 95% CI 0.805–0.837).ConclusionMHCs are common among AF patients, and they are associated with a lower rate of OAC initiation even during the NOAC era.

The PROTECT AF and PREVAIL trials demonstrated that the WATCHMAN left atrial appendage (LAA) closure device is a reasonable alternative to warfarin therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in the USA and Europe. We conducted the SALUTE trial to confirm the safety and efficacy of the LAA closure therapy for patients with NVAF in Japan. A total of 54 subjects (including 12 Roll-in) with NVAF who had a CHA2DS2-VASc score ≥2 were enrolled. All subjects were successfully implanted with the LAA closure device. No serious adverse events related to the primary procedure-safety endpoint occurred. The 2nd co-primary endpoint was a composite of all stroke, systemic embolism and cardiovascular/unexplained death. One ischemic stroke (1/42) occurred during the 6-month follow-up. The effective LAA closure rate defined as the 3rd co-primary endpoint was 100% (42/42) at both 45-day and 6-month follow-up. The procedural safety and 6-month results from the SALUTE trial demonstrated that the LAA closure device was safe and effective, similar to the results of large-scale randomized clinical trials, and provides a novel perspective of LAA closure for Japanese patients with NVAF in need of an alternative to long-term oral-anticoagulation. (Trial Registration: clinicaltrials.gov Identifier NCT 03033134).

Percutaneous left atrial appendage (LAA) closure is an emerging option for patients with atrial fibrillation at high risk for cerebrovascular events. The multicenter FLAAC registry (French Nationwide Observational LAA Closure Registry) was established to assess LAA closure outcomes in everyday practice. Four hundred thirty-six patients referred from April 2013 to September 2015 to 33 French interventional cardiology centers for percutaneous LAA closure were included prospectively in the FLAAC registry. Mean age was 75.4±0.4 years. The stroke risk was high (mean CHA2DS2-VASc score, 4.5±0.1) and most patients had experienced clinically significant bleeding (HAS-BLED score, 3.1±0.05). The device used was Amplatzer LAA occluder in 58% and the Watchman device in 42% of the patients. The procedural success rate was 98.4%. Median postprocedure follow-up was 12.0 (11.8-12.0) months and a single patient was lost to follow-up. During the periprocedural and subsequent follow-up period, procedure-related severe adverse events occurred in 21 (4.9%) and 10 (2.3%) patients, respectively. One-year cumulative incidences of ischemic stroke and cerebral hemorrhage were 2.9% (1.6-5.0) and 1.5% (0.7-3.2), respectively. Overall, 1-year mortality was 9.3% (6.9-12.5) with 7 of the 39 deaths related or possibly related to the device or procedure. This nationwide prospective registry shows that, in the French population, LAA closure is mainly used in patients with high comorbidity rates and a poor prognosis. LAA closure in such patients seems reasonable to decrease the stroke rate. The overall health status of these patients should be taken into account during the preprocedural evaluation process. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02252861.

Introduction: While appropriate oral anticoagulation in atrial fibrillation (AF) can significantly reduce the risk of stroke and is supported by evidenced-based guidelines, evidence suggests that it remains underused, or is used inappropriately. There is currently little data regarding clinicians’ perspectives on stroke prophylaxis in AF since the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs). Aims: To evaluate Australian clinicians’ attitudes in their prescribing of anticoagulants for stroke prevention in AF, including their perceptions of the safety and effectiveness of the NOACs and preferred agents. Methods: A vignette-based survey was distributed to a random sample of Australian cardiologists and general practitioners (GPs) (n=500 each), and an online version of the survey was distributed via email to all clinicians affiliated with the three major Tasmanian public hospitals. Clinicians were asked to indicate their preferred anticoagulant treatment for seven fictional patients with AF. Prescribing choices were compared against expert consensus. Additional multiple-choice and Likert-item questions addressed their use of guidelines and risk stratification tools, attitudes and perceptions. Results: Of 174 respondents (39 GPs, 40 cardiologists and 95 other hospital-based clinicians), 88% reported routinely using an AF stroke risk stratification tool but only 44.5% routinely used a bleeding risk score. Fifty-three per cent of cardiologists, 49% of GPs and 32% of other hospital-based clinicians agreed with the expert panel’s prescribing choices for four or more vignettes; this was unrelated to use of scoring tools and guidelines (p>0.05). Cardiologists were significantly (p = 0.005) more likely to favour a NOAC, with apixaban being the preferred agent. Choice of anticoagulant was also influenced by clinicians’ knowledge and confidence. Discussion: This study demonstrated that prescribing patterns varied between cardiologists, GPs and other hospitalbased clinicians. Concerns over the safety of NOACs were identified as potential barriers to their utilisation by GPs and other hospital-based clinicians. Results from the vignettes demonstrated sub-optimal prescribing choices amongst all clinicians. Further education is required to ensure all clinicians are educated and confident prescribing stroke prophylaxis in AF.

Objective We aimed to further investigate the efficacy and safety of low-dose NOACs by performing a meta-analysis of cohort studies. Background Meta-analyses of randomized controlled trials (RCTs) have demonstrated that low-dose non-vitamin K antagonist oral anticoagulants (NOACs) showed inferior efficacy compared with standard-dose NOACs, although they are still frequently prescribed for patients with atrial fibrillation (AF) in the clinical practice. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE were systematically searched from the inception to September 9, 2021, for cohort studies that compared the efficacy and/or safety of low-dose NOACs in patients with AF. The primary outcomes were ischemic stroke and major bleeding, and the secondary outcomes were mortality, intracranial hemorrhage (ICH), and gastrointestinal hemorrhage (GH). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with the random-effect model. Results Twenty-five publications involving 487856 patients with AF were included. Compared with standard-dose NOACs, low-dose NOACs had comparable risks of ischemic stroke (HR = 1.03, 95% CI 0.96 to 1.11), major bleeding (HR = 1.12, 95% CI 0.97 to 1.28), ICH (HR = 1.09, 95% CI 0.88 to 1.36), and GH (HR = 1.11, 95% CI 0.92 to 1.33), except for a higher risk of mortality (HR = 1.41, 95% CI 1.21 to 1.65). Compared with warfarin, low-dose NOACs were associated with lower risks of ischemic stroke (HR = 0.72, 95% CI .67 to 0.78), mortality (HR = 0.67, 95% CI 0.59 to 0.77), major bleeding (HR = 0.64, 95% CI 0.53 to 0.79), ICH (HR = 0.57, 95% CI 0.42 to 0.77), and GH (HR = 0.78, 95% CI 0.64 to 0.95). Conclusions Low-dose NOACs were comparable to standard-dose NOACs considering risks of ischemic stroke, major bleeding, ICH, and GH, and they were superior to warfarin. Low-dose NOACs might be prescribed effectively and safely for patients with AF. Considering limitations, further well-designed prospective studies are foreseen.