Comparative effectiveness among thromboprophylaxis strategies after the Fontan operation: A systematic review and network meta-analysis.

INTRODUCTION: A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not yet been developed. METHOD: A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events associated with these regimens. RESULTS: A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs were shown to possess a highly favorable overall profile. CONCLUSION: Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrated significantly greater efficacy than aspirin; however, they did not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tended to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies.

Obese patients with atrial fibrillation are more efficiently protected from thrombosis under warfarin or xabans compared to non-obese patients; a systematic review and Meta-analysis of six randomized controlled trials.

INTRODUCTION: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. METHODS: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. RESULTS: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. CONCLUSIONS: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.

Utility of TTR-INR guided warfarin adjustment protocol to improve time in therapeutic range in patients with atrial fibrillation receiving warfarin.

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin.

Antithrombotic drug removal with hemoadsorption during off-pump coronary artery bypass grafting.

BACKGROUND: Patients requiring coronary artery bypass grafting (CABG) are often loaded with antithrombotic drugs (AT) and are at an increased risk for perioperative bleeding complications. Active AT removal by a hemoadsorption cartridge integrated in the cardiopulmonary bypass circuit is increasingly used in this setting to reduce bleeding, and herein we describe the extension of this application in patients on AT undergoing off-pump coronary artery bypass (OPCAB). METHODS: Ten patients (80% male; mean age: 67.4 ± 9.2years) were treated with ticagrelor (eight patients), rivaroxaban and ticagrelor (one patient), and rivaroxaban (one patient) prior to OPCAB surgery. AT's were discontinued one day before surgery in nine patients and on the day of surgery in one patient, and all patients were also on aspirin. The cohort mean EuroSCORE-II was 2.9 ± 1.5%. A hemoadsorption cartridge was integrated into a dialysis device (n=4) or a stand-alone apheresis pump (n=6) periprocedural, for a treatment time of 145 ± 33 min. Outcome measures included bleeding according to Bleeding Academic Research Consortium (BARC)-4 and 24-hour chest-tube-drainage (CTD). RESULTS: Mean operation time was 184 ± 35 min. All patients received a left internal thoracic artery with a mean of 2.3 ± 0.9 total grafts. One patient had a BARC-4 bleeding event and there were no surgical re-explorations for bleeding. Mean 24-hours CTD was 680 ± 307mL. During follow-up of 19.5 ± 17.0 months, none of the patients died or required further reinterventions. No device-related adverse events were reported. CONCLUSIONS: Hemoadsorption via a stand-alone apheresis pump during OPCAB surgery was feasible and safe. This innovative and new approach showed favorable bleeding rates in patients on antithrombotic drugs requiring bypass surgery.

Ex Vivo Antiplatelet Effects of Oral Anticoagulants.

BACKGROUND: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. METHODS: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. RESULTS: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. CONCLUSIONS: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

The Prescription trends and dosing appropriateness analysis of novel oral anticoagulants in ischemic stroke patients: a retrospective study of 9 cities in China.

Background: Novel oral anticoagulants (NOACs) have been recommended by guidelines as the first-line drugs for preventing cardiogenic stroke. We aimed to provide an overview of the prescription trends and dosing appropriateness of NOACs in China. Methods: We conducted a retrospective analysis of NOAC prescriptions using the Hospital Prescription Analysis Cooperation Project data from 2016 to 2022. Various patient features, such as gender, age, city, year, source, department visited, original diagnosis, dosing, cost, and insurance type, were collected and analyzed to examine the trends and dosing appropriateness of NOAC usage in ischemic stroke patients. Results: 62,014 NOAC prescriptions were analyzed, including 16,602 for dabigatran, 45,253 for rivaroxaban, and 159 for apixaban. 85.14% of the patients were aged 65 or above, and tertiary hospitals accounted for 95.97% of NOAC prescriptions. NOAC prescriptions rose from 1828 in 2016 to 13,998 in 2021 but dropped to 13,166 in 2022. The percentage of annual prescriptions for NOACs among stroke patients has increased from 0.05% in 2016 to 0.37% in 2022. Total drug cost increased from ¥704541.18 in 2016 to ¥4128648.44 in 2021, then decreased to ¥1680109.14 in 2022. Prescriptions were divided into 48,321 appropriate and 11,262 inappropriate dosing groups, showing significant differences in medications, age, year, city type, hospital level, source, insurance type, and department visited (all p < 0.001). The median drug cost for inappropriate dosing was higher than for appropriate dosing (¥55.20 VS ¥83.80). The top comorbidities in ischemic stroke patients were atrial fibrillation (35.30%), hypertension (32.75%), and coronary heart disease (16.48%). Conclusion: The application of NOACs in the Chinese population is increasing. Our findings highlight the frequent deviation from labeled dosing of NOACs in clinical practice. Continued efforts are necessary to promote the appropriate use of NOACs according to the standard dosage in the drug insert.

The safety and efficacy of NOACs versus LMWH for thromboprophylaxis after THA or TKA: A systemic review and meta-analysis.

The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49-0.71) and adverse events (RR: 0.96; 95%CI: 0.93-0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36-0.66), apixaban (RR: 0.54; 95%CI: 0.36-0.81) and edoxaban (RR:0.49; 95%CI: 0.32-0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80-1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33-0.65), advantage events (RR: 0.87; 95%CI: 0.82-0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53-0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.

Effect of direct oral anticoagulants on bleeding during and after cataract surgery.

PURPOSE: To assess the risk for intraoperative and postoperative ocular bleeding associated with direct oral anticoagulant treatment in patients undergoing phacoemulsification surgery. METHODS: Consecutive patients had phacoemulsification and intraocular lens implantation while taking uninterrupted direct oral anticoagulants (dabigatran, rivaroxaban, or apixaban). Gender and age-matched patients without antithrombotic therapy were used as the control group. Patients were examined one week postoperatively. Intraoperative and postoperative hemorrhagic and non-hemorrhagic complications were assessed. RESULTS: Forty patients (56 eyes) on direct oral anticoagulants and 120 patients (172 eyes) without anticoagulation, at a mean age of 77 years, had phacoemulsification. There was no significant difference between the groups in the rate of intraoperative and postoperative bleeding. One eye (1.8%) in the treatment group and 3 eyes (1.7%) in the control group had hyphema (p = 0.72). No patient had thromboembolic event during or after surgery. CONCLUSIONS: Cataract surgery was safely performed while continuing direct oral anticoagulation.

Dabigatran etexilate versus warfarin in cerebral venous thrombosis in Chinese patients (CHOICE-CVT): An open-label, randomized controlled trial.

BACKGROUND: The efficacy and safety of dabigatran etexilate for Chinese patients with cerebral venous thrombosis (CVT) has not been well established. METHODS: CHOICE-CVT was an exploratory, single-center, randomized, open-label study in the National Center for Neurological Disorders involving Chinese patients with CVT aged 18 to 80 years who were randomly assigned (1:1) to either dabigatran etexilate or warfarin. Oral anticoagulants were initiated after 10-15 days of LMWH. The primary efficacy and safety endpoints included the number of patients with recurrent CVT and/or deep venous thrombosis (DVT) and major clinical bleeding within 180 days. Secondary efficacy endpoints included venous recanalization and change in papilledema at day 180. Secondary safety outcomes comprised death, clinical nonmajor bleeding, and any bleeding. The study was registered with ClinicalTrials.gov under NCT03930940. RESULTS: Between October 2017 and February 2023, a total of 89 patients were enrolled and randomly assigned to receive either dabigatran etexilate (n = 44) or warfarin (n = 45). At day 180, the dabigatran etexilate group showed a statistically nonsignificant but likely clinically significant number of patients with recurrent CVT and/or DVT (8 (18.2%; 95% CI, 6.3-30.0) vs 3 (6.7%; 95% CI, 0.0-14.2), p = 0.099, with a power (1-ß) of 38.401%) compared with the warfarin group. The dabigatran etexilate group showed a comparable number of patients with clinical major bleeding (0 (0) vs 0 (0) p = 1.000), and clinical nonmajor bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 1 (2.2%; 95% CI, 0.0-6.7)) but demonstrated a lower risk of any bleeding (1 (2.3%; 95% CI, 0.0-6.9) vs 9 (20.0%; 95% CI, 7.8-32.2)) compared with the warfarin group. Most patients in both groups achieved venous recanalization according to the Modified Qureshi scale (27 (75%; 95% CI, 60.1-89.9) in the dabigatran etexilate group vs 34 (82.9%; 95% CI, 70.9-95.0) in the warfarin group) and exhibited improvement in papilledema as per the Frisén classification (35 (97.2%; 95% CI, 91.6-100.0) in the dabigatran etexilate group vs 37 (88.1%, 95% CI, 77.9-98.3) in the warfarin group). CONCLUSIONS: These findings regarding efficacy and safety support the consideration of dabigatran etexilate therapy as a viable treatment option for Chinese patients with CVT.

Comparative Costs to Medicare and Medicare Beneficiaries of Alternative AF Stroke Risk Reduction Strategies.

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

Multiple thromboses, including intracardiac thrombi, accompanied by HIT during ECMO successfully treated with NOACs: A case report.

INTRODUCTION: Unfractionated heparin remains the mainstay of anticoagulation therapy during extracorporeal membrane oxygenation (ECMO) maintenance. However, its continued use in clinical practice exposes patients to the risk of developing heparin-induced thrombocytopenia (HIT). CASE REPORT: A 50-year-old male was diagnosed with multiple thromboses, including an intracardiac thrombi, accompanied by HIT during ECMO after cardiogenic shock related to acute myocardial infarction. The patient was successfully treated with new oral anticoagulants (NOAC), without significant complications. DISCUSSION: HIT during ECMO resulting in multiple thromboses is rare. To our knowledge, this is the first reported case of NOAC use in this context. CONCLUSION: Although thrombocytopenia and thrombosis can occur for various reasons during ECMO maintenance, it is important to consider HIT as a potential cause. NOACs can be considered as a therapeutic option.

Real-world national trends and influencing factors preference of non-vitamin K antagonist oral anticoagulants in China.

Backgrounds: Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as the first choice over warfarin for non-valvular atrial fibrillation (AF). However, there is limited data about their usage in mainland China. Methods: Prescriptions of patients diagnosed with AF and containing OACs were extracted from Hospital Prescription Cooperation Project from January 2016 to March 2021. The primary outcome was the changing percentage of different OACs. The secondary outcomes were frequencies as well as factors with the choice of different OACs and dosage of NOACs. Univariate and Multivariate logistic regressions were conducted to explore possible factors. All statistical analyses were performed using SAS software (Version 9.4). Results: Among the 220,083 distinct prescriptions diagnosed with AF and prescribed with OACs, the percentage of NOACs increased over years, exceeding warfarin in 2018. Until March 2021, 83.53% of included patients were prescribed with NOACs. Rivaroxaban (62.25%) and dabigatran (37.65%) were the most commonly prescribed NOACs. Low dosage was common for NOACs (44.54%), this was mainly driven by rivaroxaban, 67.98% of which were low dosage. Multivariate logistic regression indicated that several factors were positively associated with the preference of low dosage, including outpatients (OR 1.32, 95% CI 1.26-1.39), patients with hypertension (OR 1.49, 95% CI 1.40-1.58), acute coronary syndrome (OR 1.17, 95% CI 1.12-1.22), stroke (OR 1.42, 95% CI 1.33-1.52), and kidney disease (OR 1.63, 95% CI 1.34-1.97), as well as concomitantly using antiplatelet agents (OR 1.52, 95% CI 1.40-1.66), and steroids (OR 1.76, 95% CI 1.50-2.07). On the contrary, they were less common in health insurance holder (OR 0.79, 95% CI 0.75-0.84), patients taking apixaban (vs. rivaroxaban, OR 0.39, 95% CI 0.18-0.81), dabigatran (vs. rivaroxaban, OR 0.01, 95% CI 0.01-0.01), edoxaban (vs. rivaroxaban, OR 0.36, 95% CI 0.23-0.55), diagnosed with heart failure (OR 0.87, 95% CI 0.81-0.93), deep vein thrombosis (OR 0.36, 95% CI 0.29-0.46), pulmonary embolism (OR 0.35, 95% CI 0.28-0.43), and peripheral artery disease (OR 0.68, 95% CI 0.55-0.85). Conclusion: The usage of OACs for AF was overall complying with updated guidelines. Low dosage was common for NOACs, further studies were warranted to verify its effectiveness and explore the underlying mechanism.

Efficacy and Safety of Novel Oral Anticoagulants in Atrial Fibrillation: A Systematic Review.

In recent times, novel oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs) have emerged as an alternative to the traditionally used Vitamin K oral antagonists (VKA) like warfarin for the treatment of atrial fibrillation (AF). This systematic review and meta-analysis aims to evaluate the efficacy and safety of NOACs in patients with AF and, thus, the related thromboembolic risks and sequelae. Of the 131 published articles we examined, 11 were included in an in-depth systematic review. The articles we reviewed were from the past ten years, from 2013 onward. The analysis derived the efficacy and safety of NOACs in patients with AF and also included different patients' baseline characteristics and subgroups. This systematic review reiterates previous research findings of superior efficacy and safety of the use of NOACs in the AF population and also illuminates certain head-to-head comparisons of individual NOACs with warfarin. It digressed into subgroups of patients with different baseline characteristics to provide evidence and support the existing guidelines for the use of NOACs in the treatment of AF. Overall, there is marked efficacy and safety of NOACs in patients with AF, be they elderly or Asian, with decreased renal function, or with other comorbidities. Adherence to NOACs was also satisfactory. Despite such a review, there needs to be more research on vast subgroups and also on reversal antidotes like andexanet alfa and idarucizumab, as well as more head-to-head analysis between NOACs over a long duration of study, which would provide more answers and pinpoint reasons as to the differences that exist between demographics and subgroups in the usage of NOACs.

Prolonged Secondary Stroke Prevention with Edoxaban: A Long-Term Follow-Up of the SATES Study.

BACKGROUND: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. METHODS: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. RESULTS: Sixty-three subjects (median age 81.0 (73.5-88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2-5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.

A Rare Case of Apixaban-Induced Subdural Hematoma in Elderly Heart Failure Patient.

New oral anticoagulants (NOACs) have become more popular in the last few decades. Although apixaban has been proven to be safer than warfarin and causes less hemorrhage in comparison to other NOACs, it still poses a risk of spontaneous bleeding. We present here an 81-year-old male known case of heart failure with reduced ejection fraction (HFrEF) associated with an apical thrombus of 0.93×1.29 cm who presents with cognitive decline, slurred speech, and right side weakness following apixaban use for his apical thrombus. On further evaluation of non-contrast brain computerized tomography (CT), there was a large extra-axial subacute subdural hematoma with thick septations in the left parietal region, measuring 2.6 cm in thickness, causing an a mass effect, and an a midline shift of 1 mm. Following neurosurgery, cardiology, and anesthesiology discussions, the surgery was deferred due to his age and coexisting conditions with regular follow-ups. The patient has now gained full consciousness and is currently undergoing physiotherapy. This case highlights an elderly patient with apixaban-induced subdural hemorrhage, which is a rare entity in the medical literature. Although apixaban is safer than other NOACs, it may cause subdural hemorrhage.

Clinical outcomes in elderly atrial fibrillation patients at increased bleeding risk treated with very low dose vs. regular-dose non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.

AIMS: The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) [edoxaban 15 mg o.d., dabigatran 110 or 150 o.d., apixaban 2.5 mg o.d., or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or <10 mg o.d.] vs. regular-dosage (RD) NOACs (edoxaban 60/30 mg o.d. or other labeling-dosage NOACs) among a real-world cohort of elderly atrial fibrillation (AF) population similar to the ELDERCARE-AF cohort. METHODS AND RESULTS: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7294 and 4151 consecutive AF patients aged 80 years or older with a CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack (2 points) score ≥2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from 1 June 2012 to 31 December 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (31 December 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation [hazard ratio (HR): 1.54, 95% confidential interval (CI): 1.09-2.18; P = 0.014), venous thrombosis (HR: 3.75, 95% CI: 1.56-8.97; P = 0.003), and all-cause mortality (HR: 1.21, 95% CI: 1.15-1.29; P <0.001) compared with RD NOACs. VLD NOACs showed worse outcomes in most net clinical outcome (NCO) benefits. The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05). CONCLUSION: Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared with that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk.

Revolutionizing Treatment for Chronic Subdural Hematoma: Promising Outcomes With Middle Meningeal Artery Embolization.

Chronic subdural hematoma (cSDH) is a common condition that typically requires surgical intervention. Middle meningeal artery embolization (MMAE) has emerged as a potential alternative treatment option, although the choice of embolization material remains a topic of debate. In this case series, we report on the outcomes of 10 patients with cSDH who underwent MMAE. Most patients experienced symptom relief and a significant reduction in cSDH size post-procedure. Despite the presence of comorbidities and risk factors, most patients had positive outcomes following MMAE treatment. Only one patient required surgical intervention after the MMAE procedure due to the progression of symptoms, while MMAE successfully prevented recurrence in most patients. Our findings suggest that MMAE can be a promising treatment option for selected patients with cSDH. However, further studies are needed to compare the efficacy and safety of different embolization materials in MMAE procedures for cSDHs.

Pleiotropic effects of NOACs with focus on edoxaban: scientific findings and potential clinical implications.

Non-vitamin K antagonist oral anticoagulants (NOACs) are well-established as inhibitors of factor Xa (FXa) and thrombin in the treatment and prevention of thrombosis. However, there is growing evidence that beneficial outcomes might be based on additional pleiotropic effects beyond anticoagulation. FXa and thrombin are also known to activate protease-activated receptors (PARs), which can mediate pro-inflammatory and pro-fibrotic effects. Since PAR­1 and PAR­2 play an important role in the development of atherosclerosis, the inhibition of this pathway represents an interesting potential target for preventing the progression of atherosclerosis and fibrosis. This review focuses on potential pleiotropic effects of FXa inhibition with edoxaban seen in a variety of studies in different in vitro and in vivo test systems. As common findings from these experiments, edoxaban was able to attenuate FXa- and thrombin-induced pro-inflammatory and pro-fibrotic effects and decrease pro-inflammatory cytokine expression. In some, but not all experiments edoxaban was also shown to decrease the levels of PAR­1 and PAR­2 expression. Further studies are required to clarify the clinical implications of the pleiotropic effects mediated by NOACs.

Non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients without previous oral anticoagulants or stable under warfarin: a nationwide cohort study.

AIMS: Investigations on non-VKA oral anticoagulants (NOACs) for atrial fibrillation (AF) patients without taking any oral anticoagulants (OACs) or staying well on warfarin were limited. We aimed to investigate the associations between stroke prevention strategies and clinical outcomes among AF patients who were previously well without taking any OACs or stayed well on warfarin for years. METHODS AND RESULTS: The retrospective analysis included a total of 54 803 AF patients who did not experience an ischaemic stroke or intra-cranial haemorrhage (ICH) for years after AF was diagnosed. Among these patients, 32 917 patients who did not receive OACs were defined as the 'original non-OAC cohort' (group 1), and 8007 patients who continuously received warfarin were defined as the 'original warfarin cohort' (group 2). In group 1, compared to non-OAC, warfarin showed no significant difference in ischaemic stroke (aHR 0.979, 95%CI 0.863-1.110, P = 0.137) while those initiated NOACs were associated with lower risk (aHR 0.867, 95%CI 0.786-0.956, P = 0.043). When compared to warfarin, the composite of 'ischaemic stroke or ICH' and 'ischaemic stroke or major bleeding' was significantly lower in the NOAC initiator with an aHR of 0.927 (95%CI 0.865-0.994; P = 0.042) and 0.912 (95%CI 0.837-0.994; P < 0.001), respectively. In group 2, when compared to warfarin, those shifted to NOACs were associated with a lower risk of ischaemic stroke (aHR 0.886, 95%CI 0.790-0.993, P = 0.002) and major bleeding (aHR 0.849, 95%CI 0.756-0.953, P < 0.001). CONCLUSIONS: The NOACs should be considered for AF patients who were previously well without taking OACs and those who were free of ischaemic stroke and ICH under warfarin for years.