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Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulant therapy. The safety and efficacy of direct oral anticoagulant (DOAC) in the chronic and transitional management of CTEPH has not been investigated. We performed a retrospective analysis of 405 consecutive pulmonary endarterectomy (PEA) cases at the University of California, San Diego, from July 2015 through July 2017. PEA specimen was reviewed for the presence of acute or subacute thrombotic material distinct from the expected chronic disease removed at the time of PEA by two investigators blinded to the patient information. Of 405 PEA cases, 166 patients (41.0%) were anticoagulated with one of three available DOACs; 239 (59.0%) presented on either oral vitamin-K antagonist or chronic injectable therapy. There were no significant differences in baseline characteristics between DOAC and non-DOAC groups. Evidence of recent thrombus was observed in 22 (13.3%) in the DOAC group versus 16 (6.7%) within the non-DOAC group. The odds ratio of DOACs usage and evidence of recent thrombus was 2.34 (95% confidence interval: 1.1-5.0, p = 0.03) after adjusting for age, gender, race, body mass index, and history of antiphospholipid antibody syndrome. CTEPH patients referred for PEA while on DOAC therapy were twice as likely to have associated acute or subacute thrombi present at the time of surgery compared with those on more traditional, non-DOAC anticoagulant therapies. This raises questions of the safety and efficacy of DOACs in the chronic management of CTEPH.

Treatment of isolated and non-obstructive atherosclerotic coronary artery ectasia (CAE) is still controversial. To assess the efficacy and safety of vitamin-K antagonist (VKA) versus dual antiplatelet (DAPT) therapy in management of patients with isolated and non-obstructive atherosclerotic CAE. We prospectively enrolled 79 patients diagnosed on elective coronary angiography to have either isolated CAE or non-obstructive atherosclerotic CAE. Patients were assigned in 1:1 pattern to receive either VKA (warfarin) or DAPT (aspirin plus clopidogrel). Patients were followed-up for nine-months. The primary endpoint was the cumulative events rate including acute coronary event, target vessel intervention, or cardiac death. Analysis of cumulative events at different time intervals, its individual components, and bleeding were considered secondary endpoints. Cumulative events rate was 33%, with mortality rate of 2.5%. Both treatment groups showed comparable cumulative events during the nine-months follow-up duration. Nevertheless, Kaplan-Meier analysis beyond the first 3-months of follow-up showed significantly higher event-free survival among the VKA-group. Recurrent events (≥2) were significantly higher among the DAPT-group. Both groups showed no major bleeding events. Multivariable cox-regression analysis showed that presence of significant coronary tortuosity, use of DAPT in reference to VKA, and lower percent time in therapeutic range (%TTR) among those receiving VKA were significant independent predictors of clinical adverse events beyond the first 3-months of follow-up. Cumulative adverse events were comparable among both treatment groups for isolated non-obstructive CAE. However, adverse events were significantly more frequent in the DAPT-group beyond the first three months. [Display omitted] • Prevalence of isolated/non-obstructive atherosclerotic CAE was 1.9%. • Coronary tortuosity was among the predictors of isolated/non-obstructive CAE. • DAPT and VKA groups showed comparable cumulative events. • DAPT-group showed significantly higher recurrent events (≥2). • VKA-group showed significantly higher event-free survival beyond 3-months. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) is one of most frequent and significant challenges for emergency physicians and gastroenterologists. Mortality for upper (U) GIB is high, especially in the elderly and comorbid patients. However, there is scant evidence in the literature concerning an assessment of warfarin (VKA) and direct oral anticoagulants (DOACs) in terms of upper gastrointestinal bleeding (UGIB) severity. Aims: Using data from two different settings (Italy and the UK), we aimed to compare the impact of VKA and DOACs on the severity of UGIB. Methods: Retrospective bicentric study on adult patients under VKA or DOACs admitted either to the emergency department at the Gemelli Hospital in Rome, Italy or University College Hospital in London, UK, with suspected UGIB from 01/01/2017 to 31/12/2018. Univariate analysis with Fisher's exact test, and analysis of variance (ANOVA) were used. Results: 106 patients (62 M/44 F; mean age 71.2 ± 16.9 yrs) were enrolled and divided into the VKA group (N = 57; M: 56%, mean age: 64.9 ± 21.3 yrs) and the DOAC group (N = 49; M: 61%; mean age: 77.6 ± 12.5 yrs). At univariate analysis, the VKA group presented two endoscopic diagnoses more frequently than the DOAC group (26% vs. 8%, p < 0.05), were more frequently endoscopically treated (44% vs. 22%, p < 0.05), rescoped (12% vs. 2%, p = 0.048) and hospitalized (79% vs. 53%, p = 0.01) with a longer length of stay, LOS (VKA: 58% > 5 days vs. DOAC: 68% < 5 days, p = 0.01). There was no difference in terms of hemoglobin level on admission, however the requirement of blood transfusions was higher in the VKA group (60% vs. 41%, p = 0.041). One third of the VKA group showed a lower platelet count than the DOAC group (33% vs. 8%, p = 0.01). No statistically significant differences for in-hospital mortality were observed. For the ANOVA, the type of anticoagulant used was the only significant predictor of need to rescope (p = 0.041) and a significant co-predictor for a LOS > 5 days (p = 0.009; as well as cirrhosis, p = 0.013 and age, p = 0.005). Conclusions: Our outcomes revealed a more severe UGIB in patients on VKA, but the impact of comorbidities (i.e., more cirrhotic patients in the VKA group) cannot be disregarded. DOAC subgroup descriptive analysis, even though on a little cohort, showed higher bleeding severity for rivaroxaban. [ABSTRACT FROM AUTHOR]

Abstract Background Up to a fourth of patients at emergency department (ED) presentation suffer from acute deterioration of renal function, which is an important risk factor for bleeding events in patients on oral anticoagulation therapy. We hypothesized that outcomes of patients, bleeding characteristics, therapy, and outcome differ between direct oral anticoagulants (DOACs) and vitamin-K antagonists (VKAs). Methods All anticoagulated patients older than 17 years with an impaired kidney function treated for an acute haemorrhage in a large Swiss university ED from 01.06.2012 to 01.07.2017 were included in this retrospective cohort study. Patient, treatment, and bleeding characteristics as well as outcomes (length of stay ED, intensive care unit and in-hospital admission, ED resource consumption, in-hospital mortality) were compared between patients on DOAC or VKA anticoagulant. Results In total, 158 patients on DOAC and 419 patients on VKA with acute bleeding and impaired renal function were included. The renal function in patients on VKA was significantly worse compared to patients on DOAC (VKA: median 141 μmol/L vs. DOAC 132 μmol/L, p = 0.002). Patients on DOAC presented with a smaller number of intracranial bleeding compared to VKA (14.6% DOAC vs. 22.4% VKA, p = 0.036). DOAC patients needed more emergency endoscopies (15.8% DOAC vs, 9.1% VKA, p = 0.020) but less interventional emergency therapies to stop the bleeding (13.9% DOAC vs. 22.2% VKA, p = 0.027). Investigated outcomes did not differ significantly between the two groups. Conclusions DOAC patients were found to have a smaller proportional incidence of intracranial bleedings, needed more emergency endoscopies but less often interventional therapy compared to patients on VKA. Adapted treatment algorithms are a potential target to improve care in patients with DOAC.

OBJECTIVE: Our review aims at comparing the morbidity and mortality-related risks associated with the pre-injury administration of VK-antagonists or DOACs in elderly patients with TBI. MATERIALS AND METHODS: We performed a systematic search of the academic literature across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE), following PRISMA guidelines. We conducted a random-effect meta-analysis to compare the influence of pre-injury VK-antagonists or DOACs administration on the overall intensive care unit and hospital stays of patients with TBI. We also evaluated the overall risks associated with VK-antagonists and with DOACs for intracranial hemorrhage progression, surgical intervention, and overall mortality in patients with TBI. RESULTS: From 973 studies, we found 11 eligible with 4,991 patients with traumatic brain injury (mean age, 77.82 ± 6.76 years). Our meta-analysis revealed insignificantly higher odds of surgical intervention (OR=1.72) and mortality (OR=1.07) associated with VK-antagonists administration than with DOACs administration. Similarly, we found that the intensive care unit (Hedge's g, 0.13) and hospital (g, 0.26) stays were insignificantly longer for individuals on VK-antagonists than for those on DOAC. Moreover, we observed insignificantly higher intracranial hemorrhage progression risks (OR=1.22) for individuals receiving DOACs than for those receiving VK-antagonists. CONCLUSIONS: This study provides evidence on the morbidity and mortality-related outcomes associated with the pre-injury administration of VK-antagonists or DOACs in patients with TBI. We found no significant differences between VK-antagonists and DOACs on the overall morbidity (hospital and intensive care unit stays, intracranial hemorrhage, and surgical intervention frequency) and mortality outcomes in elderly patients with TBI. [ABSTRACT FROM AUTHOR]

Abstract Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulant therapy. The safety and efficacy of direct oral anticoagulant (DOAC) in the chronic and transitional management of CTEPH has not been investigated. We performed a retrospective analysis of 405 consecutive pulmonary endarterectomy (PEA) cases at the University of California, San Diego, from July 2015 through July 2017. PEA specimen was reviewed for the presence of acute or subacute thrombotic material distinct from the expected chronic disease removed at the time of PEA by two investigators blinded to the patient information. Of 405 PEA cases, 166 patients (41.0%) were anticoagulated with one of three available DOACs; 239 (59.0%) presented on either oral vitamin‐K antagonist or chronic injectable therapy. There were no significant differences in baseline characteristics between DOAC and non‐DOAC groups. Evidence of recent thrombus was observed in 22 (13.3%) in the DOAC group versus 16 (6.7%) within the non‐DOAC group. The odds ratio of DOACs usage and evidence of recent thrombus was 2.34 (95% confidence interval: 1.1–5.0, p = 0.03) after adjusting for age, gender, race, body mass index, and history of antiphospholipid antibody syndrome. CTEPH patients referred for PEA while on DOAC therapy were twice as likely to have associated acute or subacute thrombi present at the time of surgery compared with those on more traditional, non‐DOAC anticoagulant therapies. This raises questions of the safety and efficacy of DOACs in the chronic management of CTEPH.

This network meta-analysis was performed to rank the safety and efficacy of periprocedural anticoagulant strategies in patients undergoing atrial fibrillation ablation. MEDLINE, EMBASE, CENTRAL, and Web of Science were searched to identify randomized controlled trials comparing anticoagulant regimens in patients undergoing atrial fibrillation ablation up to July 1, 2021. The primary efficacy and safety outcomes were thromboembolic and major bleeding events, respectively, and the net clinical benefit was investigated as the primary-outcome composite. Seventeen studies were included (n = 6950). The mean age ranged from 59 to 70 years; 74% of patients were men and 55% had paroxysmal atrial fibrillation. Compared with the uninterrupted vitamin-K antagonist strategy, the odds ratios for the composite of primary safety and efficacy outcomes were 0.61 (95%CI: 0.31–1.17) with uninterrupted direct oral anticoagulants, 0.63 (95%CI: 0.26–1.54) with interrupted direct oral anticoagulants, and 8.02 (95%CI: 2.35–27.45) with interrupted vitamin-K antagonists. Uninterrupted dabigatran significantly reduced the risk of the composite of primary safety and efficacy outcomes (odds ratio, 0.21; 95%CI, 0.08–0.55). Uninterrupted direct oral anticoagulants are preferred alternatives to uninterrupted vitamin-K antagonists. Interrupted direct oral anticoagulants may be feasible as alternatives. Our results support the use of uninterrupted direct oral anticoagulants as the optimal periprocedural anticoagulant strategy for patients undergoing atrial fibrillation ablation. [ABSTRACT FROM AUTHOR]

Introduction: IV thrombolysis (IVT) is established in the unknown or extended time window based on multimodal imaging. Further, increasing evidence exists regarding IVT in patients on oral anticoagulation including direct oral anticoagulants (DOACs). However, data on IVT in ischemic stroke patients on oral anticoagulation with unknown time of stroke onset are sparse., Methods: This study bases on the longitudinal cohort study Stroke Research Consortium in Northern Bavaria (STAMINA; ClinicalTrials.gov Identifier: NCT04357899). Acute ischemic stroke patients treated with IVT in the unknown or extended time window from January 2015 to December 2019 were included. Patient selection was based on multimodal CT or MRI. Patients on oral anticoagulation (vitamin-K antagonist [VKA] or DOAC within 48 h) were eligible for IVT based on INR measurement (VKA) or plasma levels (DOAC) according to an institutional protocol. Primary outcomes were the incidence of any and symptomatic intracranial hemorrhage., Results: Of 170 ischemic stroke patients treated with IVT in the unknown or extended time window, 151 had no oral anticoagulation at stroke onset and 19 were on oral anticoagulation (6 on VKA and 13 on DOAC). The risk of symptomatic ICH according to ECASS II criteria was similar between the patients with and without oral anticoagulation (1 [5.3%] vs. 4 [2.7%], p = 0.453). After adjustment for confounding factors, pre-medication with oral anticoagulation was not associated with symptomatic ICH (aOR 1.02 [0.09-11.02], p = 0.988)., Conclusion: IVT for ischemic stroke with unknown onset appeared safe in selected patients on oral anticoagulation with both DOAC and VKA., (© 2024 S. Karger AG, Basel.)

Background : Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m 2 ) due to concerns regarding their efficacy and safety in this demographic. Aim : This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods : A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results : A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I 2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I 2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I 2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I 2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I 2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions : DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

Background: Up to a fourth of patients at emergency department (ED) presentation suffer from acute deterioration of renal function, which is an important risk factor for bleeding events in patients on oral anticoagulation therapy. We hypothesized that outcomes of patients, bleeding characteristics, therapy, and outcome differ between direct oral anticoagulants (DOACs) and vitamin-K antagonists (VKAs).Methods: All anticoagulated patients older than 17 years with an impaired kidney function treated for an acute haemorrhage in a large Swiss university ED from 01.06.2012 to 01.07.2017 were included in this retrospective cohort study. Patient, treatment, and bleeding characteristics as well as outcomes (length of stay ED, intensive care unit and in-hospital admission, ED resource consumption, in-hospital mortality) were compared between patients on DOAC or VKA anticoagulant.Results: In total, 158 patients on DOAC and 419 patients on VKA with acute bleeding and impaired renal function were included. The renal function in patients on VKA was significantly worse compared to patients on DOAC (VKA: median 141 μmol/L vs. DOAC 132 μmol/L, p = 0.002). Patients on DOAC presented with a smaller number of intracranial bleeding compared to VKA (14.6% DOAC vs. 22.4% VKA, p = 0.036). DOAC patients needed more emergency endoscopies (15.8% DOAC vs, 9.1% VKA, p = 0.020) but less interventional emergency therapies to stop the bleeding (13.9% DOAC vs. 22.2% VKA, p = 0.027). Investigated outcomes did not differ significantly between the two groups.Conclusions: DOAC patients were found to have a smaller proportional incidence of intracranial bleedings, needed more emergency endoscopies but less often interventional therapy compared to patients on VKA. Adapted treatment algorithms are a potential target to improve care in patients with DOAC. [ABSTRACT FROM AUTHOR]

Background Although the majority of clinical guidelines indicate the use of NOAC (nonvitamin K antagonist oral anticoagulant) over vitamin K antagonist in nonvalvular atrial fibrillation patients, there is no information on real-world prescription factors that lead to a specific type of oral anticoagulant selection. Objective To evaluate the prescription factors for choosing a specific oral anticoagulant for nonvalvular atrial fibrillation patients in Korea. Setting Nationwide sampled database in South Korea. Methods In this study, we defined nonvalvular atrial fibrillation patients as having one or more hospitalizations or two or more out-patient visits with a stroke risk score (CHA2DS2-VASc scores) ≥ 2 eligible for oral anticoagulant therapy from Jan 1st, 2016 to Dec 31st, 2016. Baseline characteristics were analyzed, including sex, age, comorbidities, CHA2DS2-VASc, bleeding risk score (mHAS-BLED), prescribing specialty, insurance type, medical institution type and location. Univariate and multivariate logistic regression analyses were conducted for being prescribed NOAC compared with vitamin K antagonist. Main outcome measure Adjusted odds ratio of the NOAC group and vitamin K antagonist group. Results Of 9,226 patients eligible for oral anticoagulant therapy, 4999 patients (54.2%) received oral anticoagulant therapy, and 4517 patients took NOAC or vitamin K antagonist only during the study period. Prior stroke, transient ischemic attack, thromboembolism, thyroid disease, dyslipidemia, cancer, mHAS-BLED ≥ 5, in-patient care, and specialty in internal medicine and neurology were positive predictors of NOAC use over vitamin K antagonist, whereas young age (≤64), renal dysfunction, and secondary care institution were negative predictors of NOAC use over vitamin K antagonist. Conclusions The presence of comorbidities was linked to NOAC use over vitamin K antagonist, which is different from prescription factor studies in other countries and requires further study. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are becoming increasingly popular clinically, but their safety and effectiveness profile in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is not well-established. Literature from the PubMed and EMBASE databases was systematically screened up to February 2024 to identify relevant studies on the use of DOACs in CTEPH patients. The bias risk of RCTs was assessed using the Cochrane Risk of Bias Tool 2.0. The quality of observational prospective cohorts was assessed using the Newcastle-Ottawa Scale tool. Data pooled from different studies were analyzed. Results from 4 studies were gathered, including 2 randomized controlled trials and 2 prospective cohorts, with a total of 2038 patients, of which 751 were on DOACs and 1287 were on vitamin K antagonists (VKAs). Similar rates of all-cause mortality (3.33% vs 3.33%, RD = -0.01%, 95% CI [-0.02%, 0.00%], P  = .17), VTE recurrence (1.46% vs 2.12%, RD = -0.00%, 95% CI [-0.01%, 0.01%], P  = .92) were observed. DOACs were associated with a nonsignificant reduction in bleeding events including major bleeding (2.22% vs 3.71%, RD = -0.01%, 95% CI [-0.04%, 0.01%], P  = .30), any bleeding (5.33% vs 9.94%, RD = -0.03%, 95% CI [-0.07%, 0.01%], P  = .10), and minor bleeding (4.17% vs 13.3%, RD = -0.06%, 95% CI [-0.23%, 0.10%], P  = .45). Data pooled from existing perspective trials suggests the use of DOACs in CTEPH patients as an effective and safe alternative to VKAs., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The safety and efficacy of a minimally interrupted novel oral anticoagulant (NOAC) strategy at the time of atrial fibrillation (AF) ablation is uncertain. The purpose of this study was to compare rates of bleeding and thromboembolic events between minimally interrupted NOAC and uninterrupted vitamin K antagonist (VKA) in patients undergoing AF ablation.Methods: This was a retrospective single-center cohort study of consecutive patients who underwent AF catheter ablation between January 2013 and April 2017. Endpoints included major bleeding, clinically relevant non-major bleeding and systemic thromboembolic event from the time of ablation through 30 days. Bleeding events were defined by the Bleeding Academic Research Consortium (BARC) and International Society on Thrombosis and Haemostasis (ISTH).Results: A total of 637 patients were included in the analysis, 520 patients used uninterrupted VKA and 117 patients minimally interrupted NOAC (dabigatran: n = 68; apixaban: n = 30; rivaroxaban, n = 14; edoxaban, n = 5). The rate of clinically relevant non-major bleeding was lower in the NOAC group in comparison to the VKA group (BARC type 2: 2.6% versus 8.3%, P = 0.03; ISTH: 0% versus 3.8%, P = 0.03). Rates of major bleeding were similar between groups (BARC type 3 to 5: 3.4% versus 4.2%, P = NS; ISTH: 6.0% versus 8.7%, P = NS; for NOAC and VKA groups, respectively). Rates of systemic embolism were 0% with minimally interrupted NOAC, and 0.6% with uninterrupted VKA (P = NS).Conclusions: In patients undergoing AF ablation, anticoagulation with minimally interrupted NOAC was associated with fewer clinically relevant non-major bleeding events in comparison with uninterrupted VKA without compromising thromboembolic safety. [ABSTRACT FROM AUTHOR]

Although abnormal uterine bleeding is a known adverse effect of anticoagulant drugs, true rates have not been widely studied. Society-backed recommendations and guidelines do not yet exist for prevention and management of abnormal uterine bleeding among anticoagulated patients. This study aimed to describe the incidence of new-onset abnormal uterine bleeding among patients receiving therapeutic anticoagulation by anticoagulant class, and to evaluate gynecologic treatment patterns. We conducted an institutional review board–waived retrospective chart review of female patients aged 18 to 55 years and prescribed therapeutic anticoagulants, including vitamin-K antagonists, low-molecular-weight heparins, and direct oral anticoagulants, in an urban hospital network from January 2015 through January 2020. We excluded patients with antecedent abnormal uterine bleeding and menopause. Associations between abnormal uterine bleeding, anticoagulant class, and other covariates were evaluated with Pearson chi-square and analysis-of-variance tests. The primary outcome, abnormal uterine bleeding odds by anticoagulant class, was modeled with logistic regression. Age, antiplatelet therapy, body mass index, and race were included in our multivariable model. Secondary outcomes included emergency department visits and treatment patterns. Of the 2479 patients who met the inclusion criteria, 645 were diagnosed with abnormal uterine bleeding after initiating therapeutic anticoagulation. After adjusting for age, race, body mass index, and concurrent use of antiplatelet therapy, those receiving all 3 classes of anticoagulants had higher odds of experiencing abnormal uterine bleeding (adjusted odds ratio, 2.63; confidence interval, 1.70–4.08; P <.001), whereas those taking only direct oral anticoagulants had the lowest odds (adjusted odds ratio, 0.70; confidence interval, 0.51–0.97; P =.032), with vitamin-K antagonists as the reference group. Race other than White was associated with higher odds of abnormal uterine bleeding, as was lower age. The most common hormone therapies used among patients with abnormal uterine bleeding were levonorgestrel intrauterine devices (7.6%; 49/645) and oral progestins (7.6%; 49/645). Sixty-eight patients (10.5%; 68/645) had an emergency department visit for abnormal uterine bleeding; 29.5% (190/645) of patients received a blood transfusion; 12.2% (79/645) began any pharmacologic therapy for bleeding; and 18.8% (121/645) underwent any gynecologic procedure. Abnormal uterine bleeding occurs frequently among patients on therapeutic anticoagulation. Incidence in this sample varied considerably by anticoagulant class and race; use of single-agent direct oral anticoagulation carried the lowest risk. Important sequelae such as bleeding-related emergency department visits, blood transfusions, and gynecologic procedures were common. Balancing bleeding and clotting risk in patients on therapeutic anticoagulation requires a nuanced approach and should involve collaborative management between hematologists and gynecologists. [ABSTRACT FROM AUTHOR]

Oral anticoagulation is a widely used treatment and atrial fibrillation (AF) is the most frequent indication. We review the therapeutic options on an important clinical challenge: rapid reversal anticoagulation in the setting of an urgent invasive procedure. We report a case of a 71-year-old man treated with warfarin who was over-anticoagulated when presented to the emergency department for syncope due to severe bradiarrhythmia and needed temporary pacing. Intravenous infusion of vitamin-k was not adequate for rapid reversal over anticoagulation whereas the administration of a Prothrombin Complex Concentrate (PCC) was able to quickly reverse anticoagulant activity and allowed the performance of an urgent invasive procedure without hemorrhagic complication. The aim of this paper is to draw attention to possible therapeutic strategies to reduce the risk of bleeding related to over-anticoagulation with vitamin-K antagonists (VKAs) in case of urgent invasive procedure, emphasizing the role of PCC in keeping with national and international guidelines.

Abstract: Objective: To evaluate whether low-molecular-weight heparin (LMWH) could be equally (or more) effective than oral anti-vitamin-K agents (AVK) in the long-term treatment of deep venous thrombosis (DVT). Design: A randomised, open-label trial. Material and methods: In this trial, 241 patients with symptomatic proximal DVT of the lower limbs confirmed by duplex ultrasound scan were included. After initial LMWH, patients received 6 months of treatment with full therapeutic dosage of tinzaparin or acenocoumarol. The primary outcome was the 12-month incidence of symptomatic recurrent venous thrombo-embolism (VTE). Duplex scans were performed at 6 and 12 months. Results: During the 12-month period, six patients (5%) of 119 who received LMWH and 13 (10.7%) of 122 who received AVK had recurrent VTE (p =0.11). In patients with cancer, recurrent VTE tended to be lower in the LMWH group (two of 36 [5.5%]) vs. seven of 33 [21.2%]; p =0.06). One major bleeding occurred in the LMWH group and three in the AVK group. Venous re-canalisation increased significantly at 6 months (73.1% vs. 47.5%) and at 12 months (91.5% vs. 69.2%) in the LMWH group. Conclusions: Tinzaparin was more effective than AVK in achieving re-canalisation of leg thrombi. Long-term tinzaparin was at least as efficacious and safe as AVK for preventing recurrent VTE, especially in patients with cancer. [Copyright &y& Elsevier]

We report a case of an ischemic stroke after a successful catheter ablation of atrial fibrillation (AF) and continuous oral anticoagulation therapy with direct oral anticoagulants (DOACs), which was the trigger for diagnosing antiphospholipid syndrome (APS). A 68-year-old woman underwent catheter ablation of persistent AF and continued oral anticoagulation with edoxaban at a dose of 30 mg once daily after the ablation procedure. An asymptomatic intracerebral hemorrhage was detected by brain computed tomography and magnetic resonance imaging one month post-ablation. Oral anticoagulation with dabigatran at 110 mg twice daily was continued thereafter due to a high stroke risk profile of a CHA 2 D 2 -VASc score of 3. Eight months after the procedure, the patient had multiple acute cerebral infarctions despite no apparent recurrence of atrial tachyarrhythmias and continuation of the DOAC. A blood examination revealed the presence of anti-cardiolipin-beta2-glycoproteion complex antibodies and lupus anticoagulants, and the patient was diagnosed with primary APS. The DOAC was changed to warfarin. The patient has remained free from any ischemic or hemorrhagic cerebral events for 11 months after the oral anticoagulants were changed. The ischemic stroke in the present case appeared to be associated with APS rather than AF. A diagnosis of APS may be extremely crucial in AF patients who have new-onset ischemic strokes under continuous administration of DOACs, because vitamin K antagonists are more effective for the prevention of APS-related ischemic strokes than DOACs.

Catheter ablation has been established as a rhythm control strategy in selected patients with atrial fibrillation (AF) who have failed or wish to avoid anti-arrhythmic drugs. Uninterrupted oral anticoagulation with vitamin K antagonists (VKAs) peri-ablation is associated with a lower risk of thromboembolic and bleeding complications as compared to interrupted oral anticoagulation and bridging heparin. However, a substantial portion of patients with AF are treated with non-vitamin K antagonist oral anticoagulants (NOACs). Herein, we perform an in-depth review and comparison of three recent randomized trials of uninterrupted oral anticoagulation with NOACs vs VKAs in patients undergoing AF catheter ablation. Furthermore, we report pooled results of these randomized trials. The pooled incidence of major bleeding was significantly lower with NOACs as compared to VKAs (2% vs 4.9%, respectively; odds ratio [OR] 0.40; 95% confidence intervals [CI] 0.16-0.99). Similarly, cardiac tamponade was also reduced in the NOAC group (0.4% vs 1.5%; OR 0.27; 95% CI 0.07-0.97). Thromboembolic complications were not significantly different between groups. Overall, these findings support the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement's class I recommendation for uninterrupted NOAC use in patients undergoing AF catheter ablation., (© 2018 Wiley Periodicals, Inc.)

Objectives: To evaluate the effectiveness and safety of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) among patients with non-valvular atrial fibrillation (NVAF), particularly those with chronic kidney disease (CKD)., Design: Population-based matched cohort study., Setting: Over 670 primary care practices in the UK, contributing to the Clinical Practice Research Datalink., Participants: Up to 6818 adult patients newly treated with NOACs between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high-dimensional propensity score., Interventions: Current exposure to NOACs compared with current exposure to VKAs., Main Outcome Measures: HRs of ischaemic stroke and systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding, intracranial bleeding, myocardial infarction and all-cause mortality., Results: In as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR 0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR 0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62), with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55). Similar results were obtained in on-treatment analyses using a time-dependent exposure definition., Conclusions: Our results suggest that in the UK primary care, NOACs are overall effective and safe alternatives to VKAs, among patients with NVAF altogether, as well as in patients with NVAF and CKD., Competing Interests: Competing interests: SS has received research grants, participated in advisory board meetings and/or was a speaker at conferences for Bayer, Boehringer-Ingelheim and Bristol-Myers-Squibb., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment. [ABSTRACT FROM AUTHOR]