OBJECTIVE: Oral anticoagulants (OACs) reduce the risk of ischemic stroke but may increase the risk of major bleeding in patients with non-valvular atrial fibrillation (NVAF). Various risk scores, such as HAS-BLED, ATRIA, ORBIT, and DOAC, have been proposed to assess the risk of major bleeding in patients with NVAF receiving OACs. However, limited data are available regarding bleeding risk stratification in Japanese patients with NVAF.
METHODS: Of the 16,098 NVAF patients from the J-RISK AF study, the combined data of the five major AF registries in Japan (J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and Hokuriku-Plus AF Registry), we analyzed 11,539 patients receiving OACs (median age, 71 years old; women, 29.6%; median CHA2DS2-VASc score, 3).
RESULTS: During the 2-year follow-up period, major bleeding occurred in 274 patients (1.3% per patient-year). In a multivariate Cox proportional hazards analysis, an advanced age, hypertension (systolic blood pressure ≥ 150 mmHg), bleeding history, anemia, thrombocytopenia, and concomitant antiplatelet agents were significantly associated with a higher incidence of major bleeding. We developed a novel risk stratification system, HED-[EPA]2-B3 score, which had a better predictive performance for major bleeding (C-statistics 0.67, [95% confidence interval, 0.63-0.70]) than the HAS-BLED (0.64, [0.60-0.67], P for difference 0.02) and ATRIA (0.63, [0.60-0.66], P for difference ＜0.01) scores. Furthermore, it was non-significantly higher than the ORBIT (0.65, [0.62-0.68], P for difference 0.07) and DOAC (0.65, [0.62-0.68], P for difference 0.17) scores.
CONCLUSIONS: Our novel risk stratification system, the HED-[EPA]2-B3 score, may be useful for identifying Japanese patients receiving OACs at a risk of major bleeding.

UNASSIGNED: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks.
UNASSIGNED: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk.
UNASSIGNED: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events.
UNASSIGNED: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk.
UNASSIGNED: Clinicaltrials.gov: NCT05801068.

OBJECTIVE: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear.
RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005).
CONCLUSIONS: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

OBJECTIVE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC.
METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis.
RESULTS: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome.
CONCLUSIONS: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.

The association between cancer and stroke or bleeding outcomes in atrial fibrillation is unclear. We sought to examine how certain types of cancer influence the balance between stroke and bleeding risk in patients with nonvalvular atrial fibrillation (NVAF).
We estimated stroke and bleeding risk among adult patients with NVAF and certain types of cancer (breast, prostate, colorectal, lung, and hematological cancer) from 2009 to 2019 based on data from the UK Clinical Practice Research Datalink GOLD and Aurum databases. The control group included patients with NVAF only. Of 177 065 patients with NVAF, 11379 (6.4%) had cancer (1691 breast, 3955 prostate, 1666 colorectal, 2491 hematological, and 1576 lung). Compared with patients without cancer, stroke risk was higher in patients with breast cancer (adjusted hazard ratio [aHR], 1.20 [95% CI, 1.07-1.35) and with prostate cancer (aHR, 1.11 [95% CI, 1.01-1.12) if diagnosed within 6 months before NVAF. The risk of bleeding was increased in subjects with hematological cancer (aHR, 1.55 [95% CI, 1.40-1.71]), lung cancer (aHR, 1.49 [95% CI, 1.25, 1.77]), prostate cancer (aHR, 1.38 [95% CI, 1.28-1.49]), and colorectal cancer (aHR, 1.36 [95% CI, 1.21-1.53]), but not for subjects with breast cancer. The more recent the cancer diagnosis before NVAF diagnosis (within 6 months), the higher the risk of bleeding.
Breast and prostate cancer are associated with increased stroke risk, whereas in some cancer types, the risk of bleeding seemed to exceed stroke risk. In these patients, prescribing of oral anticoagulant should be carefully evaluated to balance bleeding and stroke risk.

UNASSIGNED: Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market.
UNASSIGNED: To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF).
UNASSIGNED: Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dispensations during 2014-2022 were applied. Data on electronic dispensations during 2015-2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data.
UNASSIGNED: In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users declined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014-2018, and apixaban during 2019-2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of individuals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF.
UNASSIGNED: The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive.

Evidence regarding the risks of serious hypoglycaemia for patients with atrial fibrillation (AF) and diabetes mellitus (DM) taking antidiabetic medications with concurrent non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin is limited. This study aimed to investigate this knowledge gap.
This retrospective cohort study used nationwide data from Taiwan\'s National Health Insurance Research Database and included a total of 56 774 adult patients treated with antidiabetic medications and oral anticoagulants between 1 January 2012 and 31 December 2020. The incidence rate ratios (IRRs) of serious hypoglycaemia were estimated for patients taking antidiabetic drugs with NOACs vs. warfarin. Poisson regression models with generalized estimating equations accounting for intra-individual correlation across follow-up periods were used. Stabilized inverse probability of treatment weighting was used to create treatment groups with balanced characteristics for comparisons. Compared to concurrent use of antidiabetic drugs with warfarin, those with NOACs showed a significantly lower risk of serious hypoglycaemia (IRR = 0.73, 95% CI: 0.63-0.85, P < 0.001). In the analyses of each NOAC, patients taking dabigatran (IRR = 0.76, 95% CI: 0.63-0.91, P = 0.002), rivaroxaban (IRR = 0.72, 95% CI: 0.61-0.86, P < 0.001), and apixaban (IRR = 0.71, 95% CI: 0.57-0.89, P = 0.003) showed a significantly lower risk of serious hypoglycaemia than those taking warfarin.
In patients with AF and DM taking antidiabetic drugs, concurrent use of NOACs was associated with a lower risk of serious hypoglycaemia than concurrent use of warfarin.

UNASSIGNED: Edoxaban proved to be safe and effective also in fragile patients, but its administration through percutaneous endoscopic gastrostomy (PEG) has not been previously investigated. The purpose of this study was to evaluate the feasibility and the preliminary safety and efficacy profiles of edoxaban administered via PEG in patients with an indication for long-term oral anticoagulation.
UNASSIGNED: ORIGAMI was a prospective, single-arm, observational study (NCT04271293). Patients with PEG and an indication for long-term anticoagulation were prospectively enrolled. Crushed edoxaban at approved doses was administered via PEG. The primary endpoint was the composite of cardio-embolic events consisting of ischemic stroke, systemic embolism, or symptomatic deep venous thrombosis/pulmonary embolism (DVT/PE). Secondary endpoints were the number of bleeding events and edoxaban plasma concentrations at steady state. We here report the 12-month results.
UNASSIGNED: A total of 12 patients were enrolled. The main indication for PEG implantation was amyotrophic lateral sclerosis (10/12). The primary endpoint of cardio-embolic events did not occur in any patients at 12 months. All patients were in the therapeutic range of steady-state edoxaban plasma levels. Three minor bleedings were observed, while no major bleedings occurred during the observational period. A total of five patients died. All deaths were from non-cardiovascular causes and were consistent with the natural history of the pre-existing severe disease.
UNASSIGNED: Our study suggests that edoxaban administration via PEG is feasible and appears safe and effective in fragile, comorbid patients, resulting in therapeutic plasma concentrations of edoxaban.
UNASSIGNED: [ClinicalTrials.gov], identifier [NCT04271293].

Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen.

Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.
A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.
The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74-0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80-0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74-0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68-0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60-0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.
This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.