Aug 2026· New England Journal of Medicine· 0 citations· 19 references
Medicine
TL;DR
Among patients with atrial fibrillation at intermediate risk for stroke, DOAC therapy led to a lower risk of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months than no anticoagulation.
Abstract
Background
Current U.S. and European guidelines recommend oral anticoagulation as a class IIa indication in patients with atrial fibrillation at intermediate risk for stroke; however, evidence from randomized trials is needed.
Methods
We conducted a multicenter, open-label, adjudicator-masked superiority trial in South Korea involving patients with atrial fibrillation and an intermediate risk of stroke (a score of 1 in men and 2 in women on the CHA2DS2-VASc scale; range, 0 to 9, with higher scores indicating a greater risk of stroke). Patients were randomly assigned in a 1:1 ratio to receive either direct oral anticoagulant (DOAC) therapy or no anticoagulation. The primary end point was a composite of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months.
Results
Of 1803 patients who underwent randomization, 902 were assigned to receive DOAC therapy and 901 were assigned to receive no anticoagulant therapy. The mean age of the patients was 60.4 years, and 23.7% were women. At 24 months, a primary end-point event had occurred in 4 patients (cumulative incidence, 0.5%) in the DOAC group and in 13 (cumulative incidence, 1.5%) in the no-anticoagulant group (difference, -1.0 percentage points; 95% confidence interval [CI], -2.0 to -0.1; P = 0.03; hazard ratio, 0.31; 95% CI, 0.10 to 0.94). Stroke occurred in 3 patients (cumulative incidence, 0.3%) in the DOAC group and in 10 (cumulative incidence, 1.1%) in the no-anticoagulant group. The incidence of systemic embolism and major bleeding appeared to be similar in the two trial groups, and no deaths from cardiovascular causes occurred in either group. Serious adverse events occurred in 80 patients (8.9%) in the DOAC group and in 84 (9.3%) in the no-anticoagulant group.
Conclusions
Among patients with atrial fibrillation at intermediate risk for stroke, DOAC therapy led to a lower risk of stroke, systemic embolism, major bleeding, or death from cardiovascular causes at 24 months than no anticoagulation. (Funded by the Ministry of Health and Welfare, South Korea, and others; SINGLE-AF ClinicalTrials.gov number, NCT04437654.).
BACKGROUND
Despite the growing use of catheter ablation for atrial fibrillation, large-scale studies assessing the efficacy and safety of oral anticoagulation (OAC) after ablation, particularly in patients with high stroke risk, remain limited.
METHODS
This prospective study enrolled consecutive patients from the China-AF (China Atrial Fibrillation) registry between August 2011 and June 2022. Stroke risk was stratified by CHA2DS2-VA score as low (0-1), intermediate (2), or high (≥3). The study end points were thromboembolism (ischemic stroke or systemic embolism), and bleeding (International Society on Thrombosis and Hemostasis major bleeding and clinically relevant non-major bleeding). A 6-month landmark analysis was applied to evaluate the association of OAC with end points using incidence rates and Cox models.
RESULTS
Among 13 669 patients (median follow-up, 4.0 years), 2637 continued and 11 032 discontinued OAC at the 6-month landmark. OAC was not associated with reduced thromboembolism risk across low- (adjusted hazard ratio [aHR], 1.11 [95% CI, 0.70-1.77]; P=0.649), intermediate- (aHR, 0.64 [95% CI, 0.36-1.16]; P=0.141) or high-stroke risk patients (aHR, 1.05 [95% CI, 0.74-1.48]; P=0.801). In contrast, continued OAC was associated with higher bleeding risk, including clinically relevant non-major bleeding across stroke risk strata, and International Society on Thrombosis and Hemostasis major bleeding among high-risk patients (aHR, 2.32 [95% CI, 1.19-4.50]; P=0.013). These results were consistent across subgroups and sensitivity analyses.
CONCLUSIONS
In this large, real-world cohort of patients with atrial fibrillation undergoing catheter ablation, continued OAC was not associated with lower thromboembolic risk, but with higher major bleeding risk among patients with CHA2DS2-VA scores ≥3. These findings support individualized post-ablation anticoagulation strategies and warrant future investigation.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT06987825.
Lan Ren, Xiaodong Peng, Sitong Li et al.· Journal of the American Hear...· 0 citations
BACKGROUND
Whether direct oral anticoagulants (DOACs) are a safe and effective alternative to warfarin in patients with atrial fibrillation and mitral stenosis (AF-MS) remains controversial.
OBJECTIVE
To evaluate the effectiveness and safety of DOACs versus warfarin in patients with AF-MS.
DESIGN
Observational cohort study using target trial emulation.
SETTING
Population-wide insurance claims data in Taiwan.
PARTICIPANTS
Patients diagnosed with AF-MS and prescribed either DOACs or warfarin between 1 January 2011 and 31 December 2021 were included in the study.
INTERVENTION
DOACs or warfarin.
MEASUREMENTS
Absolute risk differences (RDs) and risk ratios (RRs) at 1 year and 5 years of follow-up for ischemic stroke, systemic embolism, composite stroke, myocardial infarction (MI), intracranial hemorrhage, gastrointestinal bleeding, bleeding at other critical sites, and all-cause death.
RESULTS
Compared with warfarin, DOACs were associated with an increased risk for ischemic stroke (RD, 4.97 percentage points [95% CI, 1.27 to 8.57 percentage points]; RR, 1.22 [CI, 1.05 to 1.41]) and composite stroke (RD, 5.56 percentage points [CI, 1.77 to 8.97 percentage points]; RR, 1.23 [CI, 1.07 to 1.42]) and a decreased risk for MI (RD, -1.61 percentage points [CI, -3.17 to -0.03 percentage points]; RR, 0.61 [CI, 0.37 to 0.99]) at the 1-year follow-up. Rivaroxaban increased the risk for ischemic stroke during both short- and long-term follow-up periods. The 2 groups did not differ in risks for bleeding or all-cause death.
LIMITATION
Limited sample size, lack of detailed information on MS severity, and lack of international normalized ratio measurements.
CONCLUSION
In Asian patients with AF-MS, DOACs were associated with an increased 1-year risk for stroke but a decreased risk for MI compared with warfarin.
PRIMARY FUNDING SOURCE
Research Grants Council of Hong Kong.
Yu Yang, Chin-Yao Shen, M. Cheng et al.· Annals of Internal Medicine· 0 citations
Perceived risk of bleeding was the leading cause for non-treatment with OACs in high-risk AF patients, and risk prediction modelling indicated that the benefits of anticoagulation in stroke and mortality reduction outweigh the risk of bleeding.
A. Kakkar, Marc P Bonaca, Robert P. Giugliano et al.· PLoS ONE· 0 citations
BackgroundNew-onset atrial fibrillation (AF) is a common complication of sepsis, affecting 5-25% of patients, and is associated with increased mortality and ischemic stroke. With limited high-quality evidence, the net clinical benefit of early oral anticoagulant (OAC) initiation in this high-risk setting remains uncertain.MethodsAdults ≥18 hospitalized with sepsis who developed new-onset AF within 3 days were identified from the TriNetX database. Cohort one included patients who received at least three doses of OAC within 3 days after AF onset and was compared to those who did not receive OAC (cohort two). Propensity score matching (1:1; 90 covariates; caliper 0.1) was employed to balance the groups. The primary outcomes assessed were evaluated at 7, 14, and 30 days. Risk ratios and risk differences with 95% confidence intervals were estimated using intention-to-treat analysis.ResultsAmong 136,172 eligible patients, 10,773 were matched per group. Early OAC use was associated with significantly lower mortality at 7, 14, and 30 days (RR 0.19-0.35; all p < 0.001) and reduced ischemic stroke risk across the same intervals (RR 0.74-0.83; p ≤ 0.004). Major bleeding rates were also lower (RR 0.40-0.49; all p < 0.001). MACEs showed a modest reduction at 7 days (RR 0.92; p = 0.001) but not afterward. Thromboembolic events were similar beyond the first week. The need for thrombolytics (RR 0.55-0.59) and anti-hemorrhagic therapy (RR≈0.69) consistently remained lower with OACs (all p < 0.001). Falsification outcomes were neutral, except for a minimal late increase for osteoarthritis at 30 days (RR 1.16; p = 0.03).ConclusionIn sepsis-associated NOAF, early OAC initiation was associated with reduced short-term mortality and ischemic stroke without excess bleeding or thromboembolic risk. The large magnitude of mortality benefit and paradoxical reduction in bleeding likely reflect residual confounding by clinical stability and patient selection. Findings warrant cautious interpretation given the observational design; prospective trials are needed.
A. Qadeer, Michele Fouad, Doaa Bayomi et al.· Journal of Intensive Care Me...· 0 citations
Background: Anticoagulation is crucial for preventing stroke and Atrial Fibrillation (AF) is a significant risk factor for thromboembolism. However, because of changed medication metabolism and coagulation profiles, treating anticoagulation in patients with concurrent Liver Disease (LD) is difficult. The safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin in patients with AF and LD are compared in this meta-analysis. Methods: A comprehensive literature search was implemented through January 2025. The study included ten observational studies that involved 417,754 patients with AF and LD. The outcomes that were evaluated included all-cause mortality, intracranial hemorrhage, stroke or systemic embolism, major bleeding and gastrointestinal bleeding. Random-effects models were employed to calculate pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs). The I² statistic was employed to evaluate heterogeneity. Results: DOACs were associated with substantially reduced risks of all-cause mortality (OR = 0.76, 95% CI: 0.58-0.99; p = 0.04), intracranial hemorrhage (OR = 0.48, 95% CI: 0.24-0.94; p = 0.03) and major bleeding (OR = 0.65, 95% CI: 0.49-0.87; p = 0.003) compared to warfarin. There were no significant differences observed in the incidence of stroke or systemic embolism (OR = 0.76, 95% CI: 0.56-1.02; p = 0.07) or gastrointestinal hemorrhage (OR = 0.97, 95% CI: 0.79-1.20; p = 0.81). Substantial heterogeneity was observed among outcomes (I²>90% in multiple analyses). Conclusion: It appears that DOACs provide comparable efficacy and enhanced safety in patients with AF and LD when compared to warfarin. Nevertheless, the observational design of the included studies and the substantial heterogeneity of the data necessitate caution in the interpretation of these results. Additional randomized controlled trials are required to verify these findings and inform clinical decision-making.
Mohamed S. Imam, Fahad Saeed Algahtani, Asim Abdullah Saleh Alqahtani et al.· Journal of Pioneering Medica...· 0 citations
BACKGROUND AND AIMS
Randomized trials demonstrated that in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) direct oral anticoagulants (DOAC) and a P2Y12 inhibitor reduce bleeding compared with vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT) with no increase in ischemic risk; however, important gaps in knowledge remain, limiting certainty and generalizability of these findings.
METHODS
In this patient-level meta-analysis of randomized trials evaluating antithrombotic strategies in patients with AF undergoing PCI, Cox proportional hazard models, stratified by trial, were used to estimate hazard ratios and 95% confidence intervals (HR, 95%CI). The primary efficacy and safety outcomes were the composite of cardiovascular death, myocardial infarction, or stroke, and TIMI major bleeding, respectively. The study was registered in PROSPERO (CRD420251130025).
RESULTS
Six trials (10,634 patients) comparing DOAC plus P2Y12 inhibitor (4,083), VKA plus single antiplatelet therapy (SAPT, 1,247), VKA plus DAPT (3,715), and DOAC plus DAPT (1,589) were included. The transition from DAPT to SAPT was recommended at 1 (1-3) and 3 (1-7) days in the DOAC plus P2Y12 inhibitor and VKA plus SAPT groups, respectively. At 1 year, the risk of the primary efficacy outcome did not differ across the antithrombotic strategies (reference group: VKA plus DAPT; DOAC plus P2Y12 inhibitor: HR 1.16, 95%CI 0.97-1.41; VKA plus SAPT: 1.14, 0.85-1.54, DOAC plus DAPT: 0.99, 0.75-1.30), without any statistically significant interaction between treatment effects and all prespecified subgroups, including age, sex, bleeding risk, and thrombotic risk. However, 14-day landmark analysis showed an increased risk of myocardial infarction and definite/probable stent thrombosis in patients receiving DOAC plus P2Y12 inhibitor or VKA plus SAPT in the early phase after PCI. DOAC plus P2Y12 inhibitor reduced the risk of the primary safety outcome compared with VKA plus DAPT (0.48, 0.38- 0.65) and VKA plus SAPT (0.62, 0.40-0.97); only a borderline reduction was observed compared to DOAC plus DAPT (0.66, 0.44-1.01). DOAC plus P2Y12 inhibitor reduced intracranial hemorrhage compared with VKA plus DAPT (0.21, 0.07-0.64).
CONCLUSIONS
In patients with AF undergoing PCI, the risk of cardiovascular death, myocardial infarction, or stroke did not significantly differ according to whether patients received a DOAC or VKA, whereas a modest increase in risk with single compared with dual antiplatelet therapy cannot be excluded, given the higher risk of early coronary events. DOACs compared with VKAs reduced the risk of bleeding across all severity grades, including intracranial hemorrhage, whereas omission of a second antiplatelet agent reduced the risk of TIMI major or minor bleeding.
M. Chiarito, R. Mehran, Michael C. Gibson et al.· European Heart Journal· 0 citations
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