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Background: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited., Aim: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI., Methods: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI., Results: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke., Conclusion: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI., (© 2024 Wiley Periodicals LLC.)

Background: Vitamin-K antagonists (VKAs) have widely been replaced by non-VKA oral anticoagulants (NOACs). This includes Austria, Germany and Switzerland, where as VKA, instead of warfarin, the much longer-acting phenprocoumon is used, which was not compared to NOACs in clinical trials., Methods: Using administrative data from a large German health insurance, we included all anticoagulation-naïve patients with a first prescription of a NOAC or VKA between 2012 and 2020. We analysed overall survival, major adverse cardiac and cerebrovascular events, major thromboembolic events and major bleeding., Results: Overall, 570,137 patients were included (apixaban: 26.9%, dabigatran: 4.6%, edoxaban: 8.8%, rivaroxaban: 39.1% and VKA: 20.7% of these 99.4% phenprocoumon). In the primary analysis using a 1:1 propensity score matching-cohort (PSM-cohort), a significantly higher overall mortality was found for apixaban, edoxaban and rivaroxaban (all p < 0.001) but not for dabigatran (p = 0.13) compared to VKA. In this PSM-cohort, 5-year mortality was 22.7% for apixaban versus 12.7% for VKA, 19.5% for edoxaban versus 11.4% for VKA, 16.0% for rivaroxaban versus 12.3% for VKA (all p < 0.001) and 13.0% for dabigatran versus 12.8% for VKA (p = 0.06). The observed effect was confirmed in sensitivity analyses using un-weighted and three different weighted Fine-Gray regression models on the basis of the entire cohort., Conclusions: In this large real-world analysis, apixaban, edoxaban and rivaroxaban, but not dabigatran, were associated with worse survival compared to VKA. These findings, consistent with a few other studies including phenprocoumon, cast profound doubts on the unreflected, general use of NOACs. Randomized trials should assess whether phenprocoumon might actually be superior to NOACs., (© 2024 BARMER Institut für Gesundheitssystemforschung and The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown., Methods: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI)., Results: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09-1.71), thrombotic events (HR 1.37, 95%CI 1.32-1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33-1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE., Conclusion: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis., (© 2024. The Author(s).)

Background: Acute pulmonary embolism (PE) is a life-threatening situation in cancer patients. In this situation, anticoagulant therapy is complex to administer due to the risk of bleeding. Only few studies have been conducted when these patients are admitted to the intensive care unit (ICU). The aim of this study was to assess the association between anticoagulation strategies as well as other factors with 90-day mortality in patients with cancer and PE admitted to ICU. Major bleeding was also evaluated according to the type of anticoagulation., Methods: Retrospective study carried out in 4 ICUs in France over a 12-year period (2009-2021). All patients with cancer and PE were included. An overlap propensity score weighting analysis was performed in the subgroup of patients treated with either unfractionated heparins (UFH) alone or low-molecular-weight heparins (LMWH) alone on 90-day mortality and major bleeding., Results: A total of 218 consecutive cancer patients admitted to ICU and presenting PE were included. The 90-day mortality rate was 42 % for the global cohort. After propensity score analysis in the subgroup of patients treated with either "UFH alone" (n = 80) or "LMWH alone" (n = 71), the 90-day mortality was similar in patients treated with UFH alone (42.6 %) vs LMWH alone (39.9 %): OR = 1.124, CI 95 % [0.571-2.214], p = 0.750. There was a significant increased toward major bleeding rates in the "UFH alone" group (25.5 %) as compared to "LMWH alone" group (11.5 %), p = 0.04., Conclusion: In 218 patients admitted to ICU and presenting PE, the 90-day mortality rate was 42 %. Treatment with UFH alone was associated with a mortality comparable to treatment with LMWH alone but it appeared to be more prone to major bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: This systematic review aims to evaluate and compare differences in clinical outcomes for adult patients diagnosed with ISSPE who were managed with anticoagulation vs clinical surveillance., Methods: PubMed, Embase, ProQuest, Cochrane, and Google Scholar were searched to identify studies evaluating the use of anticoagulation and/or clinical surveillance in patients diagnosed with ISSPE. The search included studies published up to August 3, 2023. Outcomes of interest included 90-day recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality rates., Results: Ten studies were included with a total of 1224 patients. Of these patients, 791 were treated with anticoagulation and 433 underwent surveillance. Studies found no difference in recurrent VTE rates, with the majority of studies reporting no recurrence. Of the studies that reported VTE recurrence, rates were .5% to 1.4% for the anticoagulation groups and 3.1% to 3.2% for the surveillance groups. Major bleeding rates were also similar. In anticoagulated patients, major bleeding rates ranged from 1% to 10%. In clinical surveillance patients, the majority found no rate of major bleeding, with 2 studies reporting rates of .8% to 3.2%. Mortality rates ranged widely with no significant differences reported., Conclusion: Clinical surveillance appears to be a safe and effective alternative to anticoagulation in patients with ISSPE. Ninety-day rates of recurrent VTE, major bleeding, and mortality were comparable between groups. These findings highlight the need for updated practice management guidelines to improve patient outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Falls are the leading cause of morbidity and mortality in the elderly. Non-valvular Atrial fibrillation (AF) is present in up to 9% of this group and often requires oral anticoagulation (OAC). The CHA 2 DS 2 -VASc and HAS-BLED scores are validated tools assessing risk of ischemic stroke from AF and major bleeding (MB) from OAC. It is unclear if these predictions remain accurate in post-fall patients. This study seeks to determine the stroke and major bleeding rate in atrial fibrillation patients after a ground level fall and identify if validated risk scoring systems accurately stratify risk in this cohort., Methods: Retrospective review of patients with AF presented to the emergency department after a fall. CHA 2 DS 2 -VASc and HAS-BLED scores were calculated. Follow up information was reviewed to 1 year. Patients were grouped according to discharge thromboprophylaxis plan (DTP): no treatment, Anti-platelet (AP), OAC, and AP + OAC. Outcomes were ischemic stroke, MB, or death at 1 year. Ischemic stroke and MB rates were calculated. Kruskal-Wallis, Χ 2 , Fisher's exact, and multivariable logistic regression were used to evaluate for clinical associations., Results: 192 patients were included. MB rate was 14.5 bleeds/100 person-years, and ischemic stroke rate was 10.9/100 person-years. There were no observed differences between DTPs. Overall, one-year mortality was 22.1%. On unadjusted analysis, CHA 2 DS 2 -VASc did associate with ischemic stroke (p = 0.03); HAS-BLED did not associate with MB (p = 0.17). After logistic regression accounting for known risk factors, neither system associated with ischemic stroke or MB., Conclusions: Fall patients are at higher risk for both ischemic stroke and MB compared to previously published reports. Current risk assessment tools should be used with caution. Further study of risk factors is warranted to guide medication decisions in these patients., Competing Interests: Declaration of Competing Interest No author that contributed to this work has any conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: The comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain., Objective: To compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban., Design, Setting, and Participants: Retrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older. Between January 1, 2013, and November 30, 2018, a total of 581 451 patients with atrial fibrillation began rivaroxaban or apixaban treatment and were followed up for 4 years, through November 30, 2018., Exposures: Rivaroxaban (n = 227 572) and apixaban (n = 353 879), either standard or reduced dose., Main Outcomes and Measures: The primary outcome was a composite of major ischemic (stroke/systemic embolism) and hemorrhagic (intracerebral hemorrhage/other intracranial bleeding/fatal extracranial bleeding) events. Secondary outcomes were nonfatal extracranial bleeding and total mortality (fatal ischemic/hemorrhagic event or other death during follow-up). Rates, hazard ratios (HRs), and rate differences (RDs) were adjusted for baseline differences in comorbidity with inverse probability of treatment weighting., Results: Study patients (mean age, 77.0 years; 291 966 [50.2%] women; 134 393 [23.1%] receiving reduced dose) had 474 605 person-years of follow-up (median [IQR] of 174 [62-397] days). The adjusted primary outcome rate for rivaroxaban was 16.1 per 1000 person-years vs 13.4 per 1000 person-years for apixaban (RD, 2.7 [95% CI, 1.9-3.5]; HR, 1.18 [95% CI, 1.12-1.24]). The rivaroxaban group had increased risk for both major ischemic events (8.6 vs 7.6 per 1000 person-years; RD, 1.1 [95% CI, 0.5-1.7]; HR, 1.12 [95% CI, 1.04-1.20]) and hemorrhagic events (7.5 vs 5.9 per 1000 person-years; RD, 1.6 [95% CI, 1.1-2.1]; HR, 1.26 [95% CI, 1.16-1.36]), including fatal extracranial bleeding (1.4 vs 1.0 per 1000 person-years; RD, 0.4 [95% CI, 0.2-0.7]; HR, 1.41 [95% CI, 1.18-1.70]). Patients receiving rivaroxaban had increased risk of nonfatal extracranial bleeding (39.7 vs 18.5 per 1000 person-years; RD, 21.1 [95% CI, 20.0-22.3]; HR, 2.07 [95% CI, 1.99-2.15]), fatal ischemic/hemorrhagic events (4.5 vs 3.3 per 1000 person-years; RD, 1.2 [95% CI, 0.8-1.6]; HR, 1.34 [95% CI, 1.21-1.48]), and total mortality (44.2 vs 41.0 per 1000 person-years; RD, 3.1 [95% CI, 1.8-4.5]; HR, 1.06 [95% CI, 1.02-1.09]). The risk of the primary outcome was increased for rivaroxaban in both those receiving the reduced dose (27.4 vs 21.0 per 1000 person-years; RD, 6.4 [95% CI, 4.1-8.7]; HR, 1.28 [95% CI, 1.16-1.40]) and the standard dose (13.2 vs 11.4 per 1000 person-years; RD, 1.8 [95% CI, 1.0-2.6]; HR, 1.13 [95% CI, 1.06-1.21]) groups., Conclusions and Relevance: Among Medicare beneficiaries 65 years or older with atrial fibrillation, treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.

Introduction: Anticoagulation (AC) is associated with worse outcomes after trauma in some but not all studies. To further investigate the effect of AC on outcomes in patients with splenic injury, we analyzed the Trauma Quality Programs Participant Use File (PUF) METHODS: The 2017 PUF was used to identify adult (18+ y) with all mechanisms and grades of splenic injury. Demographics, comorbidities, hospital course and outcomes were compared between AC and non-AC patients., Results: A total of 18,749 patients were included, 622 were on AC. The AC patients were older but had comparable gender composition to non-AC patients. Injury Severity Score (18.2 versus 22.5) and rates of serious (AIS ≥ 3) injury were all lower in the AC group (P = 0.001). AC patients received fewer units of RBC (5.7 versus 8.0 units, P < 0.001) and FFP (3.9 versus 5.4 units, P < 0.001) in the first 24 h but underwent angiography at similar rates (23.6 versus 24.5%, P = 0.8). Among those who underwent angiography, patients were more likely to undergo embolization if they were on AC (89.7 versus 73.9%, P = 0.04). Rates of splenic surgery were comparable (19.3 versus 21.5%, P = 0.2) between AC versus non-AC patients. Median LOS was longer in AC patients (6.3 versus 5.6 d, P = 0.002). AC patients had a higher mortality (13.3 versus 7.0%, P = 0.001). In a multivariable binary logistic regression, AC was an independent risk factor for mortality with OR 1.4 (95% CI: 1.1-1.9) CONCLUSIONS: Anticoagulation is associated with increased mortality in patients with splenic injury., Competing Interests: Disclosure The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Published by Elsevier Inc.)

Background: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis., Methods: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis., Results: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029)., Conclusion: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding., (© 2021. The Author(s).)

Objectives: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival., Design: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019)., Setting: Hospitalized patients with coronavirus disease 2019., Patients: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients., Interventions: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient., Measurements and Main Results: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation., Conclusions: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation., Competing Interests: Drs. Romero and García Aguado received support for article research from the National Institutes of Health. Dr. Moreno Munguia received support for article research from Instituto de Investigación Sanitaria del Hospital Clínico San Carlos. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40-0.62; I 2 : 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15-0.60; I 2 : 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60-4.00; I 2 : 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients., Competing Interests: The authors report no conflict of interest related to the current work. A.D.C. reports grants from ERAB (the European Foundation for Alcohol Research), outside the submitted work. Dr. Costanzo reports grants from ERAB (the European Foundation for Alcohol Research), personal fees from The Dutch Beer Institute foundation—The Brewers of Europe, outside the submitted work., (Thieme. All rights reserved.)

Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19)., Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival., Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used., Setting: 67 hospitals in the United States., Participants: Adults with COVID-19 admitted to a participating ICU., Measurements: Time to death, censored at hospital discharge, or date of last follow-up., Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35])., Limitation: Observational design., Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation., Primary Funding Source: None.

Background: Hypercoagulability may contribute to COVID-19 pathogenicity. The role of anticoagulation (AC) at therapeutic (tAC) or prophylactic doses (pAC) is unclear., Objectives: We evaluated the impact on survival of different AC doses in COVID-19 patients., Methods: Retrospective, multi-center cohort study of consecutive COVID-19 patients hospitalized between March 13 and May 5, 2020., Results: A total of 3480 patients were included (mean age, 64.5 years [17.0]; 51.5% female; 52.1% black and 40.6% white). 18.5% (n = 642) required intensive care unit (ICU) stay. 60.9% received pAC (n = 2121), 28.7% received ≥3 days of tAC (n = 998), and 10.4% (n = 361) received no AC. Propensity score (PS) weighted Kaplan-Meier plot demonstrated different 25-day survival probability in the tAC and pAC groups (57.5% vs 50.7%). In a PS-weighted multivariate proportional hazards model, AC was associated with reduced risk of death at prophylactic (hazard ratio [HR] 0.35 [95% confidence interval {CI} 0.22-0.54]) and therapeutic doses (HR 0.14 [95% CI 0.05-0.23]) compared to no AC. Major bleeding occurred more frequently in tAC patients (81 [8.1%]) compared to no AC (20 [5.5%]) or pAC (46 [2.2%]) subjects., Conclusions: Higher doses of AC were associated with lower mortality in hospitalized COVID-19 patients. Prospective evaluation of efficacy and risk of AC in COVID-19 is warranted., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: We sought to evaluate the efficacy and safety of bivalirudin versus heparin in patients with coronary artery disease undergoing transradial artery coronary intervention (TRI)., Background: Bivalirudin and radial artery access are independently associated with improved cardiovascular outcomes. However, data supporting a strategy of combining both to achieve additive improvements in cardiovascular outcomes provide conflicting results., Methods: A systematic search was performed to identify randomized controlled trials (RCTs) of bivalirudin, in which vascular access sites were reported. The primary outcome was net adverse clinical events (NACE) at 30 days. Secondary outcomes were long-term NACE, short-, and long-term major adverse cardiovascular events, all-cause mortality, myocardial infarction, unplanned revascularization, stent thrombosis, and major bleeding., Results: We identified 10 RCTs, including 16,328 patients who underwent TRI (mean age 64.6 ± 15.7 years, 72.5% male). Bivalirudin use was associated with decreased 30-day NACE compared with heparin (6.3 vs. 7.4%; risk ratio [RR] = 0.87; 95% confidence interval [CI] = 0.76-0.99; p = .04; number needed to treat = 91). No significant interactions were observed based on clinical presentation, administration of P2Y 12 inhibitors, or glycoprotein IIb/IIIa-receptor inhibitors (GPI) use. There were no significant differences between groups in any prespecified secondary outcomes. There was, however, a significant reduction of major bleeding in the bivalirudin group compared with heparin when used in combination with routine GPI (RR = 0.41; 95% CI = 0.19-0.90; p = .03)., Conclusions: Among patients undergoing TRI, use of bivalirudin was associated with significantly reduced 30-day NACE compared with heparin. There was no significant difference in long term NACE, ischemic, or bleeding events compared with heparin., (© 2020 Wiley Periodicals, Inc.)

Background: Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs)., Objective: To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription., Methods: Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test., Results: A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions., Conclusion: Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Objectives: This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH)., Background: PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH., Methods: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE., Results: The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days., Conclusions: Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications., (© 2019 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence supporting the preferential use of direct anticoagulants (DOACs) in patients with cancer, instead, is less robust so far. We therefore aimed to assess in an updated meta-analysis of randomized controlled trials whether the use of DOACs may be associated with a more favorable profile when compared to LMWH. We performed a meta-analysis of RCTs enrolling patients with VTE and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% CIs for recurrence of VTE, major bleeding, and mortality comparing subjects treated with DOACs with those with LMWH. After study selection, three RCTs (HOKUSAI-Cancer, SELECT-D and ADAM-VTE) were included for the analysis with an overall population of 1739 patients. DOACs patients had a lower incidence of 6-month recurrent VTE when compared to LMWHs (RR 0.56, 95% CI 0.40-0.79; p < 0.001). Incidence of major bleeding was not significantly different between DOACs and LMWH treated patients (RR 1.56, 95% CI 0.95-2.47, p = n.s.), and mortality rates were comparable (RR 1.03, 95% CI 0.91-2.47, p = n.s.). In a meta-analysis of RCTs therapy with DOACs was superior to LMWH in terms of efficacy and lower recurrence of VTE with a comparable safety profile in terms of bleeding events and complications.

Objectives: The aim of this study was to evaluate whether protamine administration for heparin reversal after transcatheter aortic valve replacement (TAVR) reduces bleeding complications and affects patient outcomes., Background: Occurrence of major bleeding complications in patients undergoing TAVR is associated with increased morbidity and mortality., Methods: This study included 873 patients undergoing TAVR, of whom 677 received protamine for heparin reversal. Standard access management included the use of pre-closure devices, manual compression, and percutaneous transluminal angioplasty or implantation of a covered stent graft, if necessary. The study complied with Good Clinical Practice guidelines and was approved by the local ethics committee. Written informed consent was obtained from all patients., Results: The primary endpoint, a composite of 30-day all-cause mortality and life-threatening and major bleeding, occurred less frequently in the protamine administration group (3.2%) compared with the control group (8.7%) (p = 0.003). This was driven mainly by lower rates of life-threatening and major bleeding in the protamine group (0.1% vs. 2.6% [p < 0.001] and 1.0% vs. 4.1% [p = 0.008], respectively). Furthermore, protamine administration resulted in a significantly shorter hospital stay (11.1 ± 5.8 days vs. 12.7 ± 7.8 days; p = 0.05). In the overall cohort, stroke was observed in 1.9% and myocardial infarction in 0.2% of patients, with no significant difference between the groups (p > 0.05). Multivariate analysis revealed that only protamine administration (odds ratio: 0.24; 95% confidence interval: 0.10 to 0.58; p = 0.001) and acute kidney injury (odds ratio: 5.82; 95% confidence interval: 2.02 to 16.77; p = 0.001) were independently associated with the primary endpoint., Conclusions: Protamine administration resulted in significantly lower rates of life-threatening and major bleeding complications compared with patients without heparin reversal. Occurrence of stroke and myocardial infarction was not increased by protamine administration., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- Guideline adherent oral anticoagulant (OAC) management of patients with nonvalvular atrial fibrillation has been associated with improved outcomes, but limited data are available from Asia. We aimed to investigate outcomes in patients who received guideline compliant management compared with those who were OAC undertreated or overtreated, in a large nationwide multicenter cohort of patients with nonvalvular atrial fibrillation in Thailand. Methods- Patients with nonvalvular atrial fibrillation were prospectively enrolled from 27 hospitals-all of which are data contributors to the COOL-AF Registry (Cohort of Antithrombotic Use and Optimal INR Level in Patients With Non-Valvular Atrial Fibrillation in Thailand). Patients were categorized as follows: (1) guideline adherence group when OAC was given in high-risk or intermediate-risk, but not in low-risk patients; (2) undertreatment group when OAC was not given in the high-risk or intermediate-risk groups; and (3) overtreatment group when OAC was given in the low-risk group or when OAC was given in combination with antiplatelets without indication. Results- A total of 3327 patients who had follow-up clinical outcome data were included. The mean age of patients was 67.4 years and 58.1% were male. The numbers of patients in the guideline adherence group, undertreatment group, and overtreatment group were 2267 (68.1%), 624 (18.8%), and 436 (13.1%) patients, respectively. The overall rate of ischemic stroke, major bleeding, all bleeding, and death was 3.0%, 4.4%, 15.1%, and 7.8%, respectively. Undertreated patients had a higher risk of ischemic stroke and death compared with guideline adherent patients, and overtreated patients had a higher risk of bleeding and death compared with OAC guideline-managed patients. Conclusions- Adherence to OAC management guidelines is associated with improved clinical outcomes in Asian nonvalvular atrial fibrillation patients. Undertreatment or overtreatment was found to be associated with increased risk of adverse outcomes compared with guideline-adherent management.

Objectives: Patients with major bleeding are commonly admitted to the ICU. A growing number are on either oral or parenteral anticoagulation, but the impact of anticoagulation on patient outcomes is unknown. We sought to examine this association between anticoagulation therapy and mortality, as well as the independent effects of warfarin compared to direct oral anticoagulants., Design: Analysis of a prospectively collected registry (2011-2017) of consecutive ICU patients admitted with major bleeding (as defined by International Society on Thrombosis and Haemostasis clinical criteria)., Setting: Two hospitals within a single tertiary care level hospital system., Patients: We analyzed 1,598 patients identified with major bleeding, of which 245 (15.3%) had been using anticoagulation at the time of ICU admission. Of patients on anticoagulation, 149 were using warfarin, and 60 were using a direct oral anticoagulant., Interventions: None., Measurements and Main Results: The primary outcome, in-hospital mortality, was analyzed using a multivariable logistic regression model. Patients with anticoagulation-associated major bleeding had higher in-hospital mortality (adjusted odds ratio, 1.49; 95% CI, 1.16-1.92). Among survivors, anticoagulation use was associated with longer median hospital length of stay, and higher mean costs. No differences in hospital mortality were seen between warfarin- and direct oral anticoagulant-associated major bleeding. Patients with warfarin-associated major bleeding had longer median length of stay (11 vs 6 d; p = 0.02), and higher total costs than patients with direct oral anticoagulant-associated major bleeding., Conclusions: Among ICU patients admitted with major bleeding, pre-admission anticoagulation use was associated with increased hospital mortality, prolonged length of stay, and higher costs among survivors. As compared to direct oral anticoagulants, patients with warfarin-associated major bleeding had increased length of stay and costs. These findings have important implications in the care of ICU patients with major bleeding.

Background: Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients., Methods: A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days., Results: The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke., Conclusions: In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.

Introduction: Coagulopathy due to warfarin in patients with major bleeding was traditionally reversed with fresh frozen plasma and intravenous (IV) vitamin K, but prothrombin complex concentrates (PCC) are increasingly used in the treatment of these patients. Factor Eight Inhibitor Bypassing Activity (FEIBA) is an activated four-factor PCC most commonly used in patients with hemophilia. We aimed to evaluate the efficacy and safety of FEIBA and IV vitamin K for the reversal of warfarin-associated coagulopathy in patients with major bleeding, by measuring the percentage of patients who achieved target INR ≤ 1.5 and the incidence of thrombotic adverse events (TAE)., Methods: In this prospective observational study, we enrolled patients presenting to the Emergency Department (ED) with warfarin associated coagulopathy (INR > 1.5) and major bleeding. Patients received FEIBA using an INR based dosing strategy and IV vitamin K., Results: In 43 patients, median initial INR was 4.0 (2.7, 7.3 interquartile range (IQR)). Median time to result the second INR was 45 min (38, 55 IQR) and the median INR was 1.4 (1.3, 1.6 IQR). Out of the 43 patients, 93% achieved the target INR of ≤1.5. In-hospital mortality was 40% (17 patients). There were 11 TAEs in 6 patients (14%); 4 events in 2 patients (5%) were attributed to FEIBA., Conclusion: A protocolized use of FEIBA and IV vitamin K resulted in the efficacious reversal of warfarin-induced coagulopathy in patients with major bleeding. TAEs occurred in 14% of patients and were attributed to FEIBA in 5% of patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Most real-world studies on anticoagulants have been based on health insurance databases or performed in secondary care. The aim of this study was to compare safety and effectiveness between patients treated with vitamin K antagonists (VKAs) and patients treated with direct oral anticoagulants (DOACs) in a general practice setting., Methods: The CACAO study (Comparison of Accidents and their Circumstances with Oral Anticoagulants) is a multicenter prospective cohort study conducted among ambulatory patients taking an oral anticoagulant. Participants were patients from the study's cross-sectional phase receiving oral anticoagulants because of nonvalvular atrial fibrillation, for secondary prevention of venous thromboembolism, or both. They were followed as usual for 1 year by their general practitioners, who collected data on changes in therapy, thromboembolic events, bleeding, and deaths. All events were adjudicated by an independent committee. We used a propensity score and a Cox regression model to derive hazard ratios., Results: Between April and December 2014, a total of 3,082 patients were included. At 1 year, 42 patients (1.7%) had experienced an arterial or venous event; 151 (6.1%) had experienced bleeding, including 47 (1.9%) who experienced major bleeding; and 105 (4.1%) had died. There was no significant difference between the VKA and DOAC groups regarding arterial or venous events, or major bleeding. The VKA group had a lower risk of overall bleeding (hazard ratio = 0.65; 95% CI, 0.43-0.98) but twice the risk of death (hazard ratio = 1.98; 95% CI, 1.15-3.42)., Conclusions: VKAs and DOACs had fairly similar safety and effectiveness in general practice. The substantially higher incidence of deaths with VKAs is consistent with known data from health insurance databases and calls for further research to understand its cause., (© 2020 Annals of Family Medicine, Inc.)

Aims: The aim of this study was to describe the use of antithrombotic therapy following a bleeding event among patients with myocardial infarction (MI), and the associated risk of major adverse cardiac events (MACE)., Methods and Results: Using Danish nationwide registries, patients hospitalized with a bleeding event within 1 year after MI were identified. Antithrombotic treatment with aspirin, clopidogrel, and/or vitamin K antagonists (VKA) was determined at the bleeding and at Day 90 and 180 post-bleed. Based on guidelines, patients were stratified into four groups: expected, reduced, discontinued, or intensified treatment. Risk of MACE (ischaemic stroke, MI, or death) within the first year was assessed by Cox proportional hazard models. A total of 3324 patients with a bleeding after MI were included. At Day 90 post-bleed, 1052 (31.7%) received expected antithrombotic treatment, 1301 (39.2%) reduced, 164 (4.9%) intensified, and 807 (24.3%) no treatment. Major adverse cardiac events occurred in 637 (19.2%) patients. With dual antiplatelet therapy as reference, adjusted hazard ratios for MACE were: aspirin 1.81 (1.06-3.09), clopidogrel 1.08 (0.64-1.82), VKA 1.08 (0.47-2.48), VKA + aspirin 1.97 (0.95-4.07), VKA + clopidogrel 0.26 (0.03-1.91), triple 1.73 (0.50-5.95), and no treatment 1.93 (1.11-3.36)., Conclusion: The majority of MI patients reduced or discontinued their antithrombotic therapy post-bleed. Patients in monotherapy with aspirin or no treatment post-bleed had a higher risk of MACE Further studies of optimal antithrombotic treatments after a bleed are needed., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and its prevalence increases with age. Few data are available about the clinical performance of direct oral anticoagulant (DOACs) in patients aged ≥ 80 years with AF. The aim of our propensity score matched cohort study was to compare the safety and efficacy of DOACs versus well-controlled VKA therapy among octogenarians with AF in real life setting. Data for this study were sourced from the multicenter prospectively maintained Atrial Fibrillation Research Database (NCT03760874), which includes all AF patients followed by the participating centers, through outpatient visits every 3 to 6 months. The database was queried for AF patients aged ≥ 80 years who received DOACs or VKAs treatment. The primary effectiveness endpoint was the occurrence of thromboembolic events (a composite of stroke, transient ischemic attack, systemic embolism); the primary safety endpoint was the occurrence of major bleeding; the secondary endpoint was all-cause mortality. The database query identified 774 AF patients aged ≥ 80 years treated with VKAs and 279 with DOACs. Propensity score (2:1) matching selected 252 DOAC and 504 VKA recipients. The mean follow-up was 31.07 ± 14.09 months. The incidence rate of thromboembolic events was 13.79 per 1000 person-years [14.80 in DOAC vs 13.34 in VKA group, Hazard Ratio 1.10; 95% confidence interval (CI) 0.49 to 2.45; P = 0.823]. The incidence rate of intracranial hemorrhage (ICH) was 8.06 per 1000 person-years (3.25 in DOAC vs 10.23 in VKA group, HR 0.33; 95% CI 0.07 to 1.45; P = 0.600). Through these incidence rates, we found a positive net clinical benefit (NCB) of DOACs over VKAs, equal to + 9.01. The incidence rate of all-cause mortality was 105.05 per 1000 person-years (74.67 in DOAC vs 118.67 in VKA group, Hazard Ratio 0.65; 95% CI 0.47 to 0.90; P = 0.010). The concomitant use of antiinflammatory drugs (HR 7.90; P < 0.001) were found to be independent predictor of major bleeding. Moreover, age (HR 1.17; P < 0.002) and chronic kidney disease (HR 0.34; P = 0.019) were found to be independently associated with thromboembolic events. In our study no significant difference in terms of both thromboembolic and major bleeding events, but a significant lower incidence of all-cause mortality, was detected in AF patients aged ≥ 80 years treated with DOACs vs VKAs.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major risk factor for stroke. The number of patients with AF is predicted to increase in the next few decades. AF has also negative impact on quality of life as well as it significantly increases the risk of cardiovascular disease and overall mortality. Because the stroke is a pivotal outcome of AF, its prevention with the use of anticoagulation therapy constitutes an important component of AF management. The decision on oral anticoagulants' prescription should be based on appropriate risk stratification to allow for comprehensive assessment of benefit/hazard ratio of stroke and bleeding along with patients' preference. Several risk scores for stroke and bleeding as well as for stroke and systemic embolism have been developed, mainly in patients on vitamin K antagonists. AF guidelines stress the need for repetitive evaluation of thromboembolic and bleeding risks to tailor optimal AF management. Indeed, risk is not a static "one off" process and it should be adjusted for dynamic nature of risk factors. However, most risk scores are calculated according to baseline characteristics of patients, but the older the patients get, the more comorbidities they acquire, which influences stroke risk significantly. Hence, the default management of every patient with AF should include a regular reassessment of stroke and bleeding risk factors.

Background: Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting., Methods: We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF., Results: From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63-0.78]), acute myocardial infarction (0.67; [0.57-0.79]), all-cause mortality (0.62; [0.56-0.69]), major bleeding (0.59; [0.50-0.69]), intracranial hemorrhage (0.50; [0.40-0.62]), gastrointestinal bleeding (0.66; [0.46-0.95]), and any bleeding (0.82; [0.73-0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs., Conclusions: The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.

Background: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking., Methods: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients., Results: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA 2 DS 2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months., Conclusions: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

Backgrounds: Left atrial appendage occlusion (LAAO) offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation (AF). The aim of this study was to present long-term clinical outcomes of LAAO in patients with a high risk of stroke and thromboembolic events (CHA 2 DS 2 -VAS-score ≥ 2) and bleeding (HAS-BLED score ≥ 2)., Material and Methods: A prospective, single-center study was performed in 120 patients who were screened for LAAO with the LARIAT. Out of these 89 patients were underwent LARIAT placement, were 57 had high risk of thromboembolic and bleeding risk (LAA group). Control Group consisted of patients and 31 who screened out from the LARIAT and did not undergo LAAO., Results: The mean CHA 2 DS 2 -VAS-score was 3.6 ± 1.5 versus 3.1 ± 1.2 and HAS-BLED score was 3.6 ± 1 versus 3 ± 1 compare LAA group versus control group. There were no thromboembolic events in the LAA group. In the control group thromboembolic events were observed in 9.6% (P = 0.017). Annual mortality rate was 1.8% in LAA group and 3.2% in control group (P < 0.05). Estimated bleeding risk reduction in LAA group was 62.2%., Conclusions: Long-term data confirmed that left atrial appendage closure with the LARIAT device is an effective and safe treatment in nonvalvular AF patients with high risk of stroke and bleeding., (© 2019 Wiley Periodicals, Inc.)

Purpose: To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin., Methods: We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied., Results: Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5-9 drugs, and 16% used ≥ 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0-4 vs 5-9 vs ≥ 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74-0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84-0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38-0.70) compared with warfarin., Conclusions: DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs.

Objectives . To examine the long-term risk of thromboembolism and bleeding in patients with atrial fibrillation comparing patients with and without recent breast cancer in subgroups with or without anticoagulation therapy, respectively. Design . Using nationwide registries, patients with breast cancer from 1998-2015 and subsequent atrial fibrillation within 3 years were stratified on anticoagulation and matched 1:3 on age, sex and comorbidities with atrial fibrillation patients without breast cancer. Risks of thromboembolism and bleeding were estimated by Aalen-Johansen and multivariable cox regression models. Results . Atrial fibrillation patients with and without anticoagulation were matched, respectively (201 and 525 with breast cancer matched with 603 and 1,575 without breast cancer). In patients with CHA 2 DS 2 -VASc-score >1 and anticoagulation the three years risks of thromboembolism were 4.2% (95% confidence interval (CI) 1.1-7.3) and 3.2% (CI 1.5-4.9) in patients with and without breast cancer. The risks of bleeding were 5.3% (CI 1.7-8.9) and 5.1% (CI 3.0-7.1), respectively. Breast cancer was associated with a similar risk of thromboembolism in patients with and without anticoagulation, respectively (Hazard ratio (HR) 1.10, CI 0.63-1.92 and HR 1.11, CI 0.82-1.50) and a similar risk of bleeding in patients with and without anticoagulation, respectively (HR 1.01, CI 0.56-1.84 and HR 0.85, CI 0.57-1.27) compared with the matched controls. Conclusions . Breast cancer was not associated with altered risk of thromboembolism or bleeding in patients with atrial fibrillation irrespective of treatment with anticoagulation. Our analyses suggest that atrial fibrillation diagnosed in patients with breast cancer should be considered as primary atrial fibrillation.

This study aimed to investigate the effects of anticoagulants on ultra-aged patients with nonvalvular atrial fibrillation (AF). We retrospectively studied 320 consecutive patients with AF (median age, 91 years; range 90-100.1 years). Patients were categorized as follows: patients taking direct oral anticoagulant (DOAC group, n = 93), those taking warfarin (warfarin group, n = 147), and those not taking oral anticoagulants (non-OAC group, n = 80). During the follow-up periods (median 3.00 years; first and fourth quantiles, 1.13 and 4.56 years, respectively), in thromboembolic events, the DOAC, warfarin, and non-OAC groups showed the lowest (0%, 0/93; 0%/year), intermediate (4.7%, 7/149; 1.43%/year), and highest (5%, 4/80; 2.65%/year) incidence rates, respectively. In major bleeding events, the DOAC, warfarin, and non-OAC groups showed the highest (9.67%, 9/96; 5.00%/year), intermediate (8.1%, 12/149; 2.46%/year), and lowest (0%, 0/80; 0%/year) incidence rates, respectively. These differences in the relationships of the 3 groups were statistically significant. Confounding factors did not affect these results. Bruises associated with impairment of motor function with aging caused major bleeding in approximately 60% of major bleeding cases. The Cox proportional hazards model revealed that warfarin decreased mortality, whereas antiplatelet drugs increased mortality. In conclusion, DOACs had considerably high incidence of major bleeding events, whereas absence of OAC treatment was associated with substantially high thromboembolic events. Warfarin showed acceptable incidence ratios of both events. At present, warfarin is thus believed to be adequate for ultra-aged (≥90 years) patients with nonvalvular AF. Avoidance of bruises was important to prevent major bleeding events. Antiplatelet drugs were suggested not to be adequate for these patients.

Although postdischarge bleeding (PDB) is known to negatively affect long-term outcome in patients undergoing percutaneous coronary intervention (PCI) with antiplatelet therapy (APT), the prognostic importance of PDB in patients who require both oral anticoagulants (OACs) and APT has not been fully elucidated. Among 3718 consecutive patients who underwent PCI, 302 patients were treated with both OACs and APT. We evaluated the association between PDB and 3-year all-cause mortality, as estimated by a time-updated Cox proportional hazard regression model. We performed nearest-neighbor matching on the propensity score to adjust the differences in baseline characteristics. Among 302 patients treated with OACs and APT, PDB was observed in 98 patients at a median time of 239 days. Patients experienced PDB had significantly higher incidence of 3-year all-cause mortality in the overall cohort and 94 propensity-score-matched pairs (hazard ratio 6.21, 95% confidence interval 3.29-11.72, P < 0.0001; and hazard ratio 6.13, 95% confidence interval 2.68-14.02, P < 0.0001, respectively). The risk of subsequent mortality was the highest within 180 days after PDB (58.3% within 180 days and 75.0% within 1 year). In conclusion, PDB was significantly associated with long-term mortality in patients taking both OACs and APT after PCI.

Objectives: The purpose of the study was to investigate the impact of oral anticoagulation (OAC) type on clinical outcomes 1 year after transcatheter aortic valve replacement (TAVR)., Background: Non-vitamin K oral anticoagulants (NOACs) are superior to vitamin K antagonists (VKAs) in nonvalvular atrial fibrillation (AF), while their comparative performance among patients in need of OAC undergoing TAVR is underinvestigated., Methods: The study enrolled 962 consecutive patients who underwent TAVR in 4 tertiary European centers and were discharged on either NOACs (n = 326) or VKAs (n = 636). By using propensity scores for inverse probability of treatment weighting (IPTW), the comparison of treatment groups was adjusted to correct for potential confounding., Results: Mean age and Society of Thoracic Surgeons score of the population were 81.3 ± 6.3 years and 4.5% (interquartile range: 3.0% to 7.3%); 52.5% were women and a balloon-expandable valve was used in 62.7% of cases. The primary outcome of interest, combined incidence of all-cause mortality, myocardial infarction, and any cerebrovascular event at 1-year after TAVR, was 21.2% with NOACs versus 15.0% with VKAs (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.00 to 2.07; p = 0.050, IPTW-adjusted). The 1-year incidence of any Bleeding Academic Research Consortium bleeds and all-cause mortality were comparable between the NOAC and VKA groups, 33.9% versus 34.1% (HR: 0.97; 95% CI: 0.74 to 1.26; p = 0.838, IPTW-adjusted) and 16.5% versus 12.2% (HR: 1.36; 95% CI: 0.90 to 2.06; p = 0.136, IPTW-adjusted), respectively., Conclusions: Chronic use of both NOACs and VKAs among patients in need of OAC after TAVR are comparable regarding 1-year bleeding risk. The higher ischemic event rate observed with NOACs needs to be evaluated in large randomized trials., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications., Background: PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols., Methods: This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events., Results: A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%). VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%)., Conclusion: 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding., (© 2019 British Blood Transfusion Society.)

Background: Prothrombin complex concentrate (PCC) is widely used to reverse the action of direct oral anticoagulants (DOACs) in accordance with current guidelines and because of a lack of specific reversal agents. Indications, clinical characteristics and patient outcomes of patients might differ in comparison to reversal of vitamin K antagonists where reversal with PCC is well established., Methods: Our cohort study explores patient characteristics, indications and clinical outcomes for reversal of all DOAC patients receiving PCC at our university emergency department from 01.06.2012 to 01.07.2017, in comparison with patients on VKA., Results: Out of 199,982 consultations, we studied 346 patients who were given PCC for reversal of either DOAC (n = 74) or VKA (n = 272). The most common reason for treatment was acute bleeding; in 86.7% of both groups. 37.3% of bleeding was traumatic (p = 0.666). The most frequent bleeding location was intracranial (61.6%, p = 0.881). Gastrointestinal bleeding was more often found in the DOAC group (18.9% vs. 8.8%, p = 0.014). More erythrocyte concentrates (ECs) were given to DOAC patients with blood transfusion (p = 0.014). Tranexamic acid was used more often in DOAC patients than in VKA patients (28.4% vs. 7.4%, p < 0.001). No significant group differences were found for the following patient outcomes: in-hospital mortality, ICU stay, and length of stay at the ICU or in hospital., Conclusion: In DOAC treated patients, PCC was applied more often because of gastrointestinal bleeding and patients received higher numbers of ECs as well as tranexamic acid. No differences were observed with regard to important clinical outcomes.

Objectives: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) including the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for patients with atrial fibrillation (AF)., Design: Network meta-analysis. Two authors independently extracted data. All authors evaluated overall confidence in the evidence., Results: Eighteen RCTs included in our review, a total of 78,796 patients with AF, with sample sizes from 90 to 21,105 patients. Apixaban 5 mg (OR: 0.79, 95% CI: 0.66 to 0.95), dabigatran 110 mg (0.91, 0.74-1.12), dabigatran 150 mg (0.66, 0.53-0.82), edoxaban 60 mg (0.87, 0.74-1.02), and rivaroxaban 20 mg (0.88, 0.74-1.03) reduced the risk of stroke or systemic embolism compared with warfarin. Dabigatran 150 mg had the highest P-score for reducing stroke or systemic embolic events. The risk of haemorhagic stroke and all-cause mortality was lower with all NOACs than with warfarin. Apixaban 5 mg (0.69, 0.60-0.80), dabigatran 110 mg (0.80, 0.69-0.93), dabigatran 150 mg (0.93, 0.80-1.08), edoxaban 30 mg (0.46, 0.40-0.54), and edoxaban 60 mg (0.78, 0.69-0.90) reduced the risk of major bleeding compared with warfarin. Edoxaban 30 mg had the highest P-score for reducing major bleeding. The plots of P-scores rank showed that apixaban offered the most favorable balance of efficacy and safety., Conclusions: This study adds an attempt for treatment ranking of both efficacy and safety outcomes. Future trials comparing directly NOACs are needed in order to provide conclusive proofs for these results and not only circumstantial evidence offered by a network meta-analysis.

Patients receiving vitamin K antagonists (VKAs) with an international normalized ratio (INR) between 4.5 and 10 are at increased risk of bleeding. We systematically reviewed the literature to evaluate the effectiveness and safety of administering vitamin K in patients receiving VKA therapy with INR between 4.5 and 10 and without bleeding. Medline, Embase, and Cochrane databases were searched for relevant randomized controlled trials in April 2018. Search strategy included terms vitamin K administration and VKA-related terms. Reference lists of relevant studies were reviewed, and experts in the field were contacted for relevant papers. Two investigators independently screened and collected data. Risk ratios (RRs) were calculated, and certainty of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. Six studies (1074 participants) were included in the review and meta-analyses. Pooled estimates indicate a nonsignificant increased risk of mortality (RR = 1.42; 95% confidence interval [CI], 0.62-2.47), bleeding (RR = 2.24; 95% CI, 0.81-7.27), and thromboembolism (RR = 1.29; 95% CI, 0.35-4.78) for vitamin K administration, with moderate certainty of the evidence resulting from serious imprecision as CIs included potential for benefit and harm. Patients receiving vitamin K had a nonsignificant increase in the likelihood of reaching goal INR (1.95; 95% CI, 0.88-4.33), with very low certainty of the evidence resulting from serious risk of bias, inconsistency, and imprecision. Our findings indicate that patients on VKA therapy who have an INR between 4.5 and 10.0 without bleeding are not likely to benefit from vitamin K administration in addition to temporary VKA cessation., (© 2019 by The American Society of Hematology.)

Background Available outcomes data for anticoagulation therapy in adults with congenital heart disease ( CHD ) provide assessment of global risk of this therapy for CHD patients (a heterogeneous population), but the risk of complications for the different CHD diagnoses is unknown. The purpose of the study was to describe the indications for anticoagulation, and the incidence and risk factors for major bleeding complication in adults with tetralogy of Fallot. Methods and Results We queried Mayo Adult Congenital Heart Disease (MACHD) database for tetralogy of Fallot patients (aged ≥18 years) that received anticoagulation, 1990-2017. Of 130 patients (42±14 years, 75 men [58%]), warfarin and direct oral anticoagulants were used in 125 (96%) and 5 (4%), respectively because atrial arrhythmias (n=109), mechanical prosthetic valve (n=29), intracardiac thrombus (n=4), pulmonary embolism (n=6), stroke (n=3), and perioperative anticoagulation (n=44). The median hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score for the entire cohort was 1 (0-2) and 27 (21%) had hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2. There were 14 minor bleeding events (1.6% per year) and 11 major bleeding events (1.3% per year) in 8 patients during median follow-up of 74 months (856 patient-years). Mechanical prosthesis (hazard ratio 1.78, CI 1.29-3.77, P=0.021) and hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2 (hazard ratio 1.41, CI 1.03-3.88, P=0.046) were risk factors for major bleeding events. All-cause mortality was higher in patients with major bleeding events (n=6, 75%) compared with patients without major bleeding events (n=25, 21%), P=0.001. Conclusions Considering the heterogeneity of the CHD population, data from the current study may be better suited for clinical decision-making in tetralogy of Fallot patients.

Background Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in-hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results From the nationwide SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Ad verse Outcomes With Early Implementation of the ACC /AHA Guidelines) scores. Internal and temporal validity was assessed. In-hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C-reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall ( C-index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions The 5-item SWEDEHEART score discriminates in-hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.

Objectives: To assess the efficacy and safety of bivalirudin during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in high-bleeding-risk elderly patients., Background: Bivalirudin reduces PCI-related bleeding; however, its efficacy and safety in patients with CTO, especially elderly patients with a high bleeding risk, remain unclear., Methods: This single-center prospective randomized controlled trial assigned 123 high-bleeding-risk elderly patients with CTO to either the unfractionated heparin (UFH) group (n = 55) or the bivalirudin group (n = 68). The primary efficacy endpoint was the incidence of major adverse cardiac events (MACEs) during hospitalization and at the 6-month follow-up. The safety endpoint was bleeding or procedure (access)-related complications after PCI., Results: MACE incidence was 17.6% and 20.0% in the bivalirudin and UFH groups, respectively (P = 0.82). Bleeding Academic Research Consortium (BARC) type 1-2 bleeding events during hospitalization were comparable between the groups (UFH: 10.9% vs. bivalirudin: 8.8%, P = 0.77). No BARC type 3-5 bleeding events or severe procedure (access)-related complications (subcutaneous hematoma >5 cm) occurred in either group. At the 6-month follow-up, MACE incidence was comparable between the groups (UFH: 3.6% vs. bivalirudin: 1.5%, P = 0.59). The Kaplan-Meier analysis revealed that MACE-free survival rates were comparable between the groups (P = 0.43). One case of BARC type 3-5 bleeding (fatal intracranial hemorrhage) was observed in the UFH group at the 6-month follow-up., Conclusions: Bivalirudin and UFH showed comparable efficacy and safety in elderly patients with a high bleeding risk, undergoing PCI for CTO lesions., (© 2019 Wiley Periodicals, Inc.)

Aim: There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear., Methods: Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight., Results: Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03)., Conclusion: Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women., (© 2017 Asian Pacific Society of Nephrology.)

Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (> 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation., (© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Aims: Females with atrial fibrillation (AF) have been suggested to carry a higher risk for thromboembolic events than males. We compared the residual risk of stroke, bleeding events, and cardiovascular and all-cause mortality among female and male AF patients taking warfarin., Methods and Results: Data from several nationwide registries and laboratory databases were linked with the civil registration number of the patients. A total of 54 568 patients with data on the quality of warfarin treatment (time in therapeutic range) 60 days prior to the events were included (TTR60). Gender differences in the endpoints were reported for the whole population, pre-specified age groups, and different TTR60 groups. During the 3.2 ± 1.6 years follow-up, there were no differences in the adjusted risk of stroke [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.91-1.03, P = 0.304] between the genders. Cardiovascular mortality (HR 0.82, 95% CI 0.78-0.88, P < 0.001) and all-cause mortality (HR 0.79, 95% CI 0.75-0.83, P < 0.001) were lower in women when compared with men. There were no differences in the risk of stroke, cardiovascular mortality, and all-cause mortality between the genders in the TTR60 categories except for those with TTR60 <50%. Bleeding events were less frequent in females (HR 0.52, 95% CI 0.49-0.56, P < 0.001)., Conclusion: There were no differences in the risk of stroke between female and male AF patients taking warfarin. Cardiovascular mortality, all-cause mortality, and risk of bleeding events were lower in females. Hence, female gender was not a risk marker for adverse outcomes in AF patients with proper warfarin therapy.

Background: Idarucizumab is a specific antidote for the direct thrombin inhibitor oral anticoagulant dabigatran etexilate. It has been used with increasing frequency in Australia since it was granted Therapeutic Goods Administration approval in October 2016., Aims: To assess idarucizumab usage, effect on coagulation parameters and clinical outcomes in patients who received idarucizumab in Western Sydney Local Health District (WSLHD)., Methods: A retrospective audit was conducted of all patients who received idarucizumab in WSLHD between September 2015 and December 2017., Results: Of the 23 patients who received idarucizumab, 17 (74%) had bleeding, and 6 (26%) required urgent surgery/procedure. Thrombin time (TT) or activated partial thromboplastin time (APTT, when TT not available) remained prolonged at 24 h post-idarucizumab infusion in 10 of 20 (50%) patients. Renal impairment at admission was associated with prolonged TT/APTT at 24 h (P = 0.02). Of the six (26%) patients who died during hospital admission, five had raised TT/APTT at 24 h (P = 0.05). Two deaths were due to continued bleeding despite idarucizumab. Only 17% of patients received prohaemostatic treatments, and none received plasma derivatives. Despite assay availability, dabigatran drug level was only measured in eight patients., Conclusion: Idarucizumab helped achieve haemostasis in 15 bleeding patients and allowed 6 patients to undergo urgent surgery. Half the patients had prolonged TT/APTT at 24 h post-idarucizumab, which was more likely to occur in patients with impaired renal function., (© 2018 Royal Australasian College of Physicians.)

We examined the institutional variations in anticoagulation therapy for sepsis-induced disseminated intravascular coagulation (DIC) and their effects on patient outcomes. This post hoc analysis of a cohort study included 3195 patients with severe sepsis across 42 intensive care units. To evaluate differences in the intensity of anticoagulation therapy, the proportion of patients receiving anticoagulation therapy and the total number of patients with sepsis-induced DIC were compared. Predicted in-hospital mortality for each patient was calculated using logistic regression analysis. To evaluate survival outcomes, the actual/mean predicted in-hospital mortality ratio in each institution was calculated. Thirty-eight institutions with 2897 patients were included. Twenty-five institutions treated 60% to 100% (high-intensity institutions), while the rest treated 0% to 50% (low-intensity institutions) of patients with sepsis-induced DIC having anticoagulant therapy. Every 10-unit increase in the intensity of anticoagulant therapy was associated with lower in-hospital mortality (odds ratio: 0.904). A higher number of high-intensity institutions (compared to low-intensity institutions) had lower in-hospital mortality and fewer bleeding events than predicted. In conclusion, institutional variations existed in the use of anticoagulation therapy in patients with sepsis-induced DIC. High-intensity anticoagulation therapy was associated with better outcomes.

Study Objective: The optimal management of patients receiving heparin, warfarin or direct anti-coagulant therapy who experience spontaneous, severe, life-threatening soft-tissue hemorrhage (SSTH) is unclear. The purpose of this study is to investigate efficacy and safety of the interventional protocol implemented in our department., Methods: In this retrospective cohort study, we analyzed data from 80 consecutive patients with SSTH secondary to anticoagulation therapy diagnosed by the appropriate computed tomography scan. All patients received a structured clinical pathway, including aggressive resuscitation, reversal of coagulopathy when indicated, Interventional Radiology procedures by transcatheter embolization (TE), clinical observation and repeated laboratory controls., Results: We enrolled 80 patients from 2013 to 2017. Angiography was performed in 60 patients (75%). It revealed the bleeding site in 46 cases, and a TE was performed in all. The rates of technical success of TE, primary clinical success and bleeding control were 98% (45/46), 91% (73/80) and 89% (71/80) respectively. In 5 patients (6%) the control of the bleeding was obtained with a second TE. Short-term and 30-day mortality was 5% (4 patients) and 11% (9 patients), respectively. No adverse events were observed., Conclusion: A structured clinical pathway, including TE seems to be an effective and safe method to manage the patients with SSTH due to anticoagulant treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The benefits and harm caused by anticoagulant treatments for sepsis induced disseminated intravascular coagulation (DIC) remain unclear. Therefore, we performed a network meta-analysis to assess the effect of available anticoagulant treatments on patient mortality, DIC resolution and the incidence of bleeding complication in patients with septic DIC., Materials and Methods: We considered all studies from four recent systematic reviews and searched the PubMed, MEDLINE, and Cochrane databases for other studies that investigated anticoagulant treatment for septic DIC using antithrombin, thrombomodulin, heparin, or protease inhibitors in adult critically ill patients. These four anticoagulants and placebo were compared. The primary outcome in this study was patient mortality, and the secondary outcomes were the DIC resolution rate and incidence of bleeding complications., Results: The network meta-analysis included 1340 patients from nine studies. There were no significant differences in the risks of mortality and bleeding complications among all direct comparisons and the network meta-analysis. Using a placebo was associated with a significantly lower rate of DIC resolution, compared to antithrombin in the direct comparison (odds ratio [OR]: 0.20, 95% credible interval [95% CrI]: 0.046-0.81) and in the network meta-analysis (OR: 0.20, 95% CrI: 0.043-0.84)., Conclusions: Our study revealed no significant differences in the risks for mortality and bleeding complications when a placebo and all four anticoagulants were compared in septic DIC patients. The results also indicated that antithrombin was associated with a five-fold higher likelihood of DIC resolution, compared to placebo., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The optimal management of major bleeding in patients receiving vitamin K antagonists (VKA) for venous thromboembolism (VTE) is unclear., Methods: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to assess the management and 30-day outcomes after major bleeding in patients receiving VKA for VTE., Results: From January 2013 to December 2017, 267 of 18,416 patients (1.4%) receiving long-term VKA for VTE had a major bleeding (in the gastrointestinal tract 78, intracranial 72, hematoma 50, genitourinary 20, other 47). Overall, 151 patients (57%) received blood transfusion; 110 (41%) vitamin K; 37 (14%) fresh frozen plasma; 29 (11%) pro-haemostatic agents and 20 (7.5%) a vena cava filter. During the first 30 days, 59 patients (22%) died (41 died of bleeding) and 13 (4.9%) had a thrombosis. On multivariable analysis, patients with intracranial bleeding (hazard ratio [HR]: 4.58; 95%CI: 2.40-8.72) and those with renal insufficiency at baseline (HR: 2.73; 95%CI: 1.45-5.15) had an increased mortality risk, whereas those receiving vitamin K had a lower risk (HR: 0.47; 0.24-0.92). On the other hand, patients receiving fresh frozen plasma were at increased risk for thrombotic events (HR: 4.22; 95%CI: 1.25-14.3)., Conclusions: Major bleeding in VTE patients receiving VKA carries a high mortality rate. Intracranial bleeding and renal insufficiency increased the risk. Fresh frozen plasma seems to increase this risk for recurrent VTE., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected. These NCCN Guidelines Insights explain recent changes in anticoagulants recommended for the treatment of cancer-associated VTE., (Copyright © 2018 by the National Comprehensive Cancer Network.)