Direct Oral Anticoagulants In Patients Research Articles

Acute Ischaemic Stroke in Patients Treated with Direct Oral Anticoagulants: Potential Causes, Clinical Characteristics, and Short-Term Outcomes.

Direct oral anticoagulants (DOAC) are the first-line treatment for primary and secondary acute ischaemic stroke (AIS) prevention in patients with nonvalvular atrial fibrillation (NVAF), but a significant percentage of patients develop AIS despite being treated with DOAC. As the number of DOAC-treated patients is growing, so is the number of patients with AIS on DOAC. The aim of the study was to assess the incidence of AIS with prestroke DOAC treatment among patients hospitalised in the University Hospital in Kraków, to analyse the clinical characteristics of AIS occurring in patients on DOAC, and to identify potential causes of treatment ineffectiveness in this group. In the study, we included all patients hospitalised in the Department of Neurology of the University Hospital in Kraków within one year (July 2022 to June 2023) with the diagnosis of AIS. The group was divided into two subgroups of patients with and without prestroke DOAC treatment. Based on medical files, we retrospectively analysed the profile of cardiovascular risk factors, stroke severity (assessed with National Institutes of Health Stroke Scale, NIHSS), use of causative stroke treatment and short-term outcomes (defined as NIHSS score, modified Rankin scale (mRS) score at discharge, in-hospital mortality, and secondary intracerebral haemorrhage among patients treated with mechanical thrombectomy, MT). Within the DOAC-treated subgroup, we looked for potential causes of AIS occurring despite DOAC treatment (valvular AF, poor adherence to treatment, underdosing, other prothrombotic conditions, aetiology of stroke other than thromboembolic, and drug-drug interactions). In the study, we included 768 AIS patients. 109 (14.2%) had a history of prestroke DOAC treatment. A potential cause of DOAC treatment failure was identified in the majority of them (n = 63, 57.8%). Patients with prestroke DOAC treatment had worse functional condition before stroke and higher stroke severity on admission but similar short-term outcomes and similar short-term effects of treatment with MT. DOAC (+) and DOAC (-) patients had different profiles of cardiovascular risk factors and different factors associated with short-term outcome. Conclusions and Clinical Implications. A potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented.

Direct oral anticoagulants compared with warfarin in patients with left ventricular thrombus: a cohort study from China.

Current guidelines recommend vitamin K antagonist (VKA) for left ventricular (LV) thrombus. This study aimed to compare the effectiveness and safety of direct oral anticoagulant (DOAC) and warfarin in Chinese patients with LV thrombus. Patients with LV thrombus admitted to Beijing Anzhen Hospital of Capital Medical University between January 2018 and January 2022, were enrolled in this cohort study. The primary endpoint was defined as thrombus resolution within 90 days. The secondary endpoints included thrombus resolution within 180 days, major bleeding events, and minor bleeding events. All patients were followed up for at least 90 days after diagnosis of LV thrombus. Patients were divided into the VKA and DOAC groups according to the anticoagulants. Differences in clinical endpoint events between the two groups were compared. This study included 129 and 111 patients in the VKA and DOAC groups, respectively. After adjusting for gender and smoking status, no significant difference was observed in thrombus resolution within 90 days between the VKA and DOAC groups. Additionally, there was no difference between the two groups in the secondary endpoints of thrombus resolution within 180 days, major bleeding, and minor bleeding. In subgroup analysis, rivaroxaban and dabigatran did not show significant differences in primary and secondary endpoints. This study showed no significant difference in thrombus resolution between DOAC and warfarin. DOAC might be an alternative to warfarin for the treatment of LV thrombus. However, further large prospective studies are required to explore the efficacy and safety of DOAC in patients with LV thrombus.

Efficacy and Safety of Direct Oral Anticoagulants in Cerebral Venous Thrombosis: Meta-Analysis of Randomized Clinical Trials.

Current guidelines recommend the standard-of-care anticoagulation (vitamin K antagonists or low-molecular-weight heparin) in patients with cerebral venous thrombosis (CVT). Herein, we performed a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy and safety of direct oral anticoagulants (DOACs) compared with the current standard of care in patients with CVT. We systematically searched the PubMed and Embase databases up to December 2023 to identify clinical trials on the effect of DOACs in patients with CVT. A Mantel-Haenszel fixed effects model was applied, and the effect measures were expressed as the absolute risk differences (RDs) and 95% confidence intervals (CIs). A total of 4 RCTs involving 270 participants were included. In the pooled analysis, DOACs and standard of care had low incidence rates of recurrent VTE and all-cause death, and similar rates of any recanalization (78.2% vs 83.2%; RD = -4%, 95%CI:-14% to 5%) and complete recanalization (60.9% vs 69.4%; RD = -7%, 95%CI:-24% to 10%). Compared with the standard of care, DOACs had non-significant reductions in the rates of major bleeding (1.2% vs 2.4%; RD = -1%, 95%CI: -6% to 3%), intracranial hemorrhage (1.9% vs 3.6%; RD = -2%, 95%CI:-7% to 3%), clinically relevant non-major bleeding (3.8% vs 7.4%; RD = -4%, 95%CI:-9% to 2%), and any bleeding (17.3% vs 21.4%; RD = -4%, 95%CI:-16% to 8%) in patients with CVT. DOACs and standard of care showed similar efficacy and safety profiles for the treatment of CVT. DOACs might be safe and a convenient alternative to vitamin K antagonists for thromboprophylaxis in patients with CVT.

Effect of Direct Oral Anticoagulants in Patients with Splanchnic Vein Thrombosis: A Systematic Reviews and Meta-Analysis.

Since several studies have examined the use of direct oral anticoagulants (DOACs) in treating patients with splanchnic vein thrombosis (SVT), we conducted a meta-analyses to assess the safety and efficacy of DOACs compared to vitamin K antagonists (VKAs) in this population. We conducted a comprehensive search using the PubMed, Embase, and Cochrane Library databases until June 2024. We used odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures to compare DOACs with VKAs. A total of 9 observational studies were included. The pooled analysis revealed that a trend towards higher complete recanalization rates with DOACs (71.4%) compared to VKAs (55.3%), though not statistically significant (OR 1.95; 95%CI 0.70 to 5.44). For SVT extension, a significant effect was observed favoring DOACs (OR 0.12; 95%CI 0.03 to 0.54). No significant differences were found in other efficacy outcomes or safety outcomes, except for major bleeding, which was significantly lower with DOACs (OR 0.27; 95%CI 0.13 to 0.56). DOACs are superior to VKAs in SVT extension and major bleeding, suggesting that DOACs may be a favorable treatment option in the treatment of SVT.

Infrequent transition to direct oral anticoagulants in patients with cancer.

Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. Not relevant.

Lower rate of major bleeding in very high risk patients undergoing left atrial appendage occlusion: A propensity score–matched comparison with direct oral anticoagulant

BackgroundLong-term oral anticoagulation is the mainstay therapy for thromboembolic (TE) prevention in patients with atrial fibrillation. However, left atrial appendage occlusion (LAAO) could be a safe alternative to direct oral anticoagulants (DOACs) in patients with a very high TE risk profile. ObjectiveThe purpose of this study was to compare the safety and efficacy of LAAO vs DOACs in patients with atrial fibrillation at very high stroke risk (CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category] score ≥ 5). MethodsData from patients with CHA2DS2-VASc score ≥ 5 were extracted from a prospective multicenter database. To attenuate the imbalance in covariates between groups, propensity score matching was used (covariates: CHA2DS2-VASc and HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] scores), which resulted in a matched population of 277 patients per group. The primary end point was a composite of cardiovascular death, TE events, and clinically relevant bleeding during follow-up. ResultsOf 2381 patients, 554 very high risk patients were included in the study (mean age 79 ± 7 years; CHA2DS2-VASc score 5.8 ± 0.9; HAS-BLED score 3.0 ± 0.9). The mean follow-up duration was 25 ± 11 months. A higher incidence of the composite end point was documented with DOACs compared with LAAO (14.9 events per 100 patient-years in the DOAC group vs 9.4 events per 100 patient-years in the LAAO group; P = .03). The annualized clinically relevant bleeding risk was higher with DOACs (6.3% vs 3.2%; P = .04), while the risk of TE events was not different between groups (4.1% vs 3.2%; P = .63). ConclusionIn high-risk patients, LAAO had a similar stroke prevention efficacy but a significantly lower risk of clinically relevant bleeding when compared with DOACs. The clinical benefit of LAAO became significant after 18 months of follow-up.

Central American and Caribbean Consensus Document for the Optimal Management of Oral Anticoagulation in Patients with Non-Valvular Atrial Fibrillation Endorsed by the Central American and Caribbean Society of Arterial Hypertension and Cardiovascular Prevention.

Atrial fibrillation (AF) is the most common arrhythmia in adults. Prevention of the ischaemic risk with oral anticoagulants (OACs) is widely recommended, and current clinical guidelines recommend direct oral anticoagulants (DOACs) as preference therapy for stroke prevention. However, there are currently no clinical practice guidelines or recommendation documents on the optimal management of OACs in patients with AF that specifically address and adapt to the Central American and Caribbean context. The aim of this Delphi-like study is to respond to doubts that may arise in the management of OACs in patients with non-valvular AF in this geographical area. A consensus project was performed on the basis of a systematic review of the literature, a recommended ADOLOPMENT-like approach, and the application of a two-round Delphi survey. In the first round, 31 recommendations were evaluated and 30 reached consensus, of which, 10 unanimously agreed. The study assessed expert opinions in a wide variety of contextualized recommendations for the optimal management of DOACs in patients with non-valvular atrial fibrillation (NVAF). There is a broad consensus on the clinical practice guideline (CPG) statements used related to anticoagulation indication, patient follow-up, anticoagulation therapy complications, COVID-19 management and prevention, and cardiac interventions.

Clinical Course and Management of Patients with Emergency Surgery Treated with Direct Oral Anticoagulants or Vitamin K Antagonists-Results of the German Prospective RADOA-Registry.

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) (p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients (p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site (p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants in Low Body Weight Patients with Atrial Fibrillation: A Systematic Review and Meta-analysis.

Direct oral anticoagulant (DOAC) agents are established as the anticoagulation strategy of choice for a variety of clinical risks. Despite this, uncertainty still exists with regard to their efficacy and safety for the prevention of stroke and systemic embolism in some patient populations; most notably those with low body weight (LBW) (<60 kg or body mass index [BMI] <18 kg/m2). Currently, there is a paucity of trial and non-trial data to support a prescriptive recommendation for their use in these patient cohorts. We have carried out a pooled systematic review of the most up to date published data of patients stabilized on various DOAC analogs with the view to ascertaining the exact matrices of their efficacy and safety in these cohorts of patients. We initially carried out a comprehensive search of databases from inception to June 2023 for eligible studies exploring the efficacy and safety of various analogs of direct oral anticoagulants in patients with atrial fibrillation who had low body weight. Databases accessed include PubMed, EMBASE, the Science Citation Index, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness. We carried out a weighted comparison of derived pooled odd ratios (with their corresponding confidence intervals) of mortality outcomes between various DOACs using the random effects model. Thirteen studies (n = 165,205 patients) were included in our meta-analysis. DOAC analogs were associated with increased stroke-related events, composite outcome, and mortality in low body weight patients compared to non-low body weight patients (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.17-1.92), (OR 1.55, 95% CI 1.29-1.86), (OR 2.92, 95% CI 1.87-4.58), respectively. There was no significant difference in the safety outcome (major bleeding events) between the DOAC analogs (OR 1.19, 95% CI 0.93-1.52). In this meta-analytical review comprising both real-world and randomized controlled studies, the use of DOAC analogs in low body weight patients (body weight of <60 kg or BMI<18 kg/m2) with atrial fibrillation was associated with increased risks of stroke-related events, composite outcomes, and mortality compared to non-low body weight cohorts patients. At the same time, there was no significant difference in terms of major bleeding events. This finding has provided the first resolution of pervading uncertainty surrounding the use of DOAC analogs in these patient cohorts and suggests the need for follow-up confirmatory systematic studies in this group of patients.

АНТИКОАГУЛЯНТНАЯ ТЕРАПИЯ У БОЛЬНЫХ С ФИБРИЛЛЯЦИЕЙ ПРЕДСЕРДИЙ И ЦИРРОЗОМ ПЕЧЕНИ

Atrial fibrillation is one of the most common arrhythmias. In patients with liver cirrhosis, the presence of atrial fibrillation is accompanied by additional risks of thromboembolic complications and death. Prevention of thromboembolic events in patients with liver dysfunction presents significant difficulties due to the presence of coagulopathies, which contribute to an increased risk of thrombus formation and hemorrhagic events. Warfarin and direct oral anticoagulants in patients with mild to moderate liver dysfunction and concomitant atrial fibrillation are comparable in effectiveness in reducing the risk of ischemic stroke, but direct oral anticoagulants demonstrate a better safety profile due to reduced risk of bleeding. Clinical trials evaluating the efficacy and safety of anticoagulants rarely include patients with severe liver impairment (Child-Pugh class C), and the benefit of anticoagulant therapy in this population requires further study.

Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Effectiveness and safety of apixaban and rivaroxaban vs warfarin in patients with atrial fibrillation and chronic kidney disease.

Randomized controlled trials (RCTs) of direct oral anticoagulants (DOACs) included a low proportion of atrial fibrillation (AF) patients with chronic kidney disease (CKD), and suggested that DOACs are safe and effective in patients with mild-to-moderate CKD. In a metanalysis of RCTs and observational studies, DOACs were associated with better efficacy (vs warfarin) in early CKD and had similar efficacy and safety profiles in patients with stages IV-V CKD. But few studies have provided data on the safety and effectiveness of each DOAC vs warfarin in patients with stage III CKD. The effectiveness and safety of DOACs in those patients are still subject to debate. To assess and compare the effectiveness and safety of apixaban and rivaroxaban vs warfarin in this patient population. A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed apixaban and rivaroxaban was created using the administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs warfarin initiation. Treatment groups were compared in an under-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. A total of 8899 included patients filled out a new oral anticoagulation therapy claim; 3335 for warfarin and 5564 for DOACs. Compared with warfarin, 15 mg and 20 mg rivaroxaban presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk [Hazard ratio (HR) 0.76; 95% confidence interval (CI): 0.65-0.88] and a similar safety risk (HR 0.94; 95%CI: 0.66-1.35). Apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95%CI: 0.79-1.26) and a lower safety risk (HR 0.65; 95%CI: 0.43-0.99. Although, apixaban 5.0 mg was associated with a better effectiveness (HR 0.76; 95%CI: 0.65-0.88), but a similar safety risk profile (HR 0.94; 95%CI: 0.66-1.35). The observed improvement in the effectiveness composite for apixaban 5.0 mg was driven by a reduction in mortality (HR 0.61; 95%CI: 0.43-0.88). In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin

BackgroundLittle to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease. ObjectivesTo assess the effectiveness and safety of direct oral anticoagulants (DOACs)—individually and as a class—vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease. MethodsWe conducted a retrospective, US claims–based, propensity score–matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding. ResultsThe cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02). ConclusionWhile the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.

Safety and Efficacy of Direct Oral Anticoagulants in Patients with Liver Cirrhosis: A Systematic Review and Meta-Analysis

Introduction Direct oral anticoagulants (DOACs) are widely used for treatment of venous thromboembolism (VTE) and stroke prophylaxis in patients with atrial fibrillation. Liver cirrhosis increases the risk of conditions necessitating anticoagulation, but also increases the risk of bleeding, complicating anticoagulation use. Traditionally, low molecular weight heparin (LMWH) or Vitamin K Antagonists (VKA) have been used in this patient population. However, VKA use can be complicated due to difficulty monitoring in the context of synthetic dysfunction and baseline INR abnormalities. DOACs have emerged as alternative agents, with less proposed reliance on hepatic elimination. Apixaban, rivaroxaban, edoxaban and dabigatran are eliminated by the liver at 75%, 65%, 50% and 20% respectively. However, safety data on DOACs in cirrhosis patients is limited due to historic exclusion from larger trials. Patients with severe Child-Pugh (CP) classes are notably underrepresented in major trials. Various guidelines currently classify CP class C (and sometimes B) as contraindications to DOACs. Methods A literature search of MEDLINE and Embase from inception to Jan 2023 identified randomized controlled trials (RCTs) and cohort studies comparing DOACs to LMWH/VKA in cirrhosis patients. Two independent reviewers screened and extracted data at title, abstract, and full-text. Patient characteristics, CP class, and anticoagulation regimens were extracted. The primary outcome was major bleeding per ISTH criteria. Secondary outcomes include clinically relevant non-major bleeding (CRNMB) and minor bleeding per ISTH criteria as a composite outcome, VTE incidence, and arterial thromboembolism (ATE) incidence. Results were stratified into two subgroups: CP B&amp;C Exclusive, and CP Unspecified (primary study did not report or stratify by CP class). A meta-analysis was conducted using the Mantel-Haenszel random-effects model and presented as odds ratios (OR) with corresponding 95% confidence intervals (CI). Results Of 794 articles screened, 21 articles (2 RCTs, 1 prospective cohort, 13 retrospective cohorts, 5 abstracts) were included for analysis (n = 5738). Overall, DOACs were associated with a lower risk of major bleeding compared to controls (OR=0.63 [0.45, 0.89], p&amp;lt;0.01). This result was consistent in the CP B&amp;C Exclusive subgroup (OR=0.42 [0.29, 0.62], p&amp;lt;0.01, 5 studies) but not in the CP Unspecified subgroup (OR=0.71 [0.48, 1.08], p=0.11, 13 studies). One large study (n=3213), Lawal 2023, weighed 20.1% in the CP B&amp;C Exclusive group, favoured DOACs in reduction of major bleeding (OR=0.37, 95%CI [0.24,0.57]). Removal of this study in a post-hoc sensitivity analysis led to no differences in major bleeding in the CP B&amp;C subgroup (OR=0.79, 95%CI [0.31,1.97]), CP Unspecified subgroup (OR=0.71, 95%CI [0.48,1.08]), or overall bleeding (OR=0.75, 95%CI [0.55,1.03]). For CRNMB and minor bleeding, DOACs did not differ from control overall or in any subgroups. DOACs significantly reduced the risk of VTE in the CP Unspecified subgroup and overall. The difference in VTE incidence was non-significant in the CP B&amp;C Exclusive subgroup, however the analysis only had two studies. The difference in ATE incidence in the overall sample and all subgroups was non-significant. Conclusion In this analysis comparing DOACs to LMWH/VKAs in patients with liver cirrhosis, DOACs were associated with a statistically significant reduction in the risk of major bleeding overall and in the more advanced subgroups (CP B&amp;C). The association between DOACs and the risk of CRNMB and minor bleeding was non-significant. Patients using DOACs had lower VTE incidence compared to those using LMWH/VKA, with no difference in ATE incidence. Limitations include the inability to stratify CP class B and C due to limited CP class C evidence, reducing confidence in our ability to differentiate a differing effect in these two groups. Furthermore, a single large study (Lawal 2023), heavily influenced the major bleeding outcome; its removal shifted the conclusion from favouring DOACs to non-significant differences. Nevertheless, these results provide reassurance on the safety profile of DOACs in comparison to LMWH/VKA in patients with cirrhosis, particularly in those with moderate to severe liver cirrhosis, a population of clinical uncertainty. There is no concerning evidence for future trials, which are much needed, to include this population.

Quality of Oral Anticoagulation with Vitamin K Antagonists and Direct Oral Anticoagulants in ‘real-World’ Patients: Lessons from a Five Years Audit Study

Background: Even with the introduction of direct oral anticoagulants (DOACs), anticoagulation clinics (ACs) stand with a key role in monitoring. Indeed, routine evaluation by health care professionals is recommended as it is with vitamin K antagonists (VKA) with adjustments in practices of anticoagulation management services. Quality of oral anticoagulation (QOA) is associated to better clinical outcomes in those patients with indications for such therapy. It is well established that patients receiving VKA therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. It has been reported that ACs should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. So far, QOA for DOACs is not fully established. Aim: Since few clinical data are available considering the new era of ACs, this study aims to describe actual trends and QOA of an AC at a large academic medical hospital. Methodology: We retrospectively analyzed 23275 appointments of 5 consecutive years (May 2018 to May 2023), corresponding to 930 patients that are regularly followed up at an outpatient AC of a central hospital under anticoagulation for at least 8 weeks. TTR (≥70%) determined by Rosendaal method was used for patients under AVK and for those individuals in DOACs, QOA was considered the presence of therapeutic plasma levels of the drugs after the European Heart Rhythm Association 2021 in, at least, one determination. Patients were divided according to target INR in 3 groups: Group 1 with target INR 2-3, including 809 patients mean age 65±18 years (mean±SD), majority (36.6%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 92 patients with mean age 70±11 years, majority (85.9%) with mechanical heart valves; Group 3 with target INR 3-4, including 29 patients with mean age 63±15 years, majority (55.5%) with antiphospholipid syndrome. Seventy patients were under DOACs (apixaban in 74.3%), with mean age of 71±17 years, majority (62.9%) with non-valvular AF, were included in Group 1 and all individuals were under direct inhibitors of factor Xa. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests were performed. Results: The 930 patient population, 52.2% female, mean age of 65±18 years and 87% in Group 1, showed a mortality of 17%. The mean recall interval between appointments was superior to 90 days in 94% of the population. The individuals who died in comparison with the survivors showed higher frequency of AF (54.1%) [ χ 2= 47.099; p&amp;lt;.001; φ=.225], were from Group 1 (93%) [ χ 2= 6.641; p=.036; φ=.085], male (59.2%) [ χ 2= 10.103; p=.001; φ=-.104] and older [76±12 vs .63±18 years (p&amp;lt;.001), respectively]. No differences were noticed in mortality between AVK and DOACs [ χ 2= 1.828; p=.401; φ=-.044], even DOAC patients being older than AVK patients (71±17 vs 65±17; p=.005), respectively. QOA associated with mortality being the individuals who died with higher frequency of no QOA (21.9% vs 13.9%) [ χ 2= 8.126; p=.004; φ=-.101] respectively. The individuals on AVK from Group 1 corresponding to 86% of total population showed a mean TTR of 76%, patients from Group 2 had a TTR of 72% and patients in Group 3 had TTR of 55%. From the individuals under DOACs, only 30% had at least one determination of plasma levels of the drug and all but one showed therapeutic levels. Comparatively with our previous studies related to the periods of 2006-2012 and 2012-2018, we noticed a significant decrease in patient population / appointments size (2087/ 61988) (1587/ 37931),(p &amp;lt;.001) with an increase of TTR in Group 1 (1927/1430 patients) (83% /72%) and Group 2 (120/125 patients) (74% / 69%) but a TTR decrease in Group 3 (40 / 32 patients) (54% / 60%) (p &amp;lt;.001). respectively. Mortality in the 2012- 2018 period was 18%. Conclusions and Discussion: The trends of decreasing the number of anticoagulated patients at our AC with an overall good quality of monitoring but with a low percentage of individuals under DOACs suggests that the majority of anticoagulated population is on these drugs without routine follow up in opposition to the recent recommendations. Our study underlines the importance of the quality of anticoagulation monitoring on mortality that was no different from the previous years before SARS-CoV- 2 pandemic nor between AVK and DOACs.

Initial anticoagulation therapy with direct oral anticoagulants in patients with intermediate-high-risk pulmonary embolism: from the COMMAND VTE Registry-2

Abstract Background Patients with intermediate-high-risk pulmonary embolism (PE) who have both right ventricular dysfunction and elevated cardiac biomarkers are at a high risk of early hemodynamic decompensation and circulatory collapse, and it might be reasonable to treat these patients with parenteral anticoagulation therapy before switching to oral anticoagulation therapy. Recently, initial direct oral anticoagulants (DOACs) therapy in patients with PE have been shown to be non-inferior compared with initial parenteral anticoagulation therapy followed by vitamin K antagonist, which might be also a potential alternative for patients with intermediate-high-risk PE. However, the effectiveness and safety of initial DOACs therapy in this patient population have not been well investigated. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 Japanese medical centers in the DOAC era between January 2015 and August 2020. The current study population consisted of 515 patients with intermediate-high-risk PE who were normotensive and right ventricular dysfunction on echocardiography or computed tomography, accompanied by elevated troponin levels (troponin I &amp;gt;0.028 ng/mL or troponin T &amp;gt;0.014 ng/mL) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide (BNP) levels (NT-proBNP ≥600 pg/mL or BNP ≥100 pg/mL). The patients were divided into 2 groups; patients with initial DOACs therapy (N=107) and those with initial parenteral anticoagulation therapy (N=408). Results Most of baseline characteristics were comparable between the 2 groups. The 1-year cumulative incidence of bleeding events was significantly lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy (6.5% vs. 15.3%, P=0.007) (Figure 1A), whereas the 1-year cumulative incidence of VTE recurrence was comparable between the 2 groups (2.2% vs. 2.2%, P=0.62) (Figure 1B). The 1-year incidence of all-cause mortality was numerically lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy without statistically significant difference (4.5% vs. 13.5%, P=0.06) (Figure 1C). Conclusions Initial DOACs therapy in patients with intermediate-high-risk PE showed no signal of worse outcomes compared with initial parenteral anticoagulation therapy, which could be a potential initial anticoagulation strategy in this patient population.Figure 1

Usefulness of low-dose direct oral anticoagulants for peripheral deep vein thrombosis of the lower extremities in cancer patients with cancer bleeding lesions

Abstract Background Venous thromboembolism (VTE) is a frequent complication in cancer patients. VTE is often detected as asymptomatic peripheral deep vein thrombosis (DVT). Standard doses of anticoagulants are generally considered difficult to administer in cancer patients due to the high risk of bleeding. However, it has been reported that peripheral DVT worsening to proximal DVT in cancer patients due to increased coagulation tendency, and some strategy for peripheral DVT is required. And the adverse bleeding effects of DOACs have been reported to be dose-dependent. Purpose The aim of this study was to determine the optimal treatment strategy of peripheral DVT in patients with bleeding cancer lesions. In order to do this we compared no anticoagulation, low-dose direct oral anticoagulants (DOACs) and standard-dose DOACs in patients with and without bleeding cancer lesions. Methods A total of 224 consecutive patients with peripheral DVT of the lower extremities (excluding pulmonary thromboembolism or proximal DVT) were included from April 2019 to March 2020. Of these, 172 patients could be followed up by repeated ultrasound examinations for up to 2 years. We investigated retrospectively the change in ultrasound findings between first and second examinations (median interval 44 days). 163 patients were studied, excluding 9 patients who used warfarin or heparin. In 119 of these DOACs were applied, and 44 were without anticoagulation. If the treatment procedure had changed between the first and second ultrasound examinations main treatment procedure was selected and categorized. Results All the patients of low-dose and standard-dose DOACs groups had no major bleeding during follow up period. In the group with cancer bleeding lesion (n=45) there were 12 patients (70.1%) worsening DVT in the group without anticoagulation, 1 patient (4.3%) in the low-dose DOACs and 0 (0%) in the standard-dose DOACs group. There was significant worsening of DVT in the no anticoagulant group compared with low-dose DOACs (P&amp;lt;0.0001), but no significant difference between low-dose DOACs and standard-dose DOACs (P=0.63) in the group with bleeding (see Figure 1). In the group without cancer bleeding (n=118), worsening of DVT occurred in 16 patients (59.3%) without anticoagulation, in 6 patients (16.7%) with low-dose DOACs and in 4 patients (7.3%) with standard-dose DOACs. There was significant worsening of DVT in the no anticoagulant group compared with low-dose DOACs (P&amp;lt;0.0001), but no significant difference between the low-dose and standard-dose DOACs (P=0.16) in the group without bleeding (see Figure 2). Conclusion Low-dose DOACs were found to be as effective as standard-dose DOACs in treating peripheral DVT in cancer patients, with or without bleeding of the cancer lesion. Peripheral DVT treatment with low-dose DOACs can reduce worsening of DVT and should be one of the supportive treatments for the completion of cancer management.DVT in 3 groups with cancer bleedingDVT in 3 groups without cancer bleeding

Direct oral anticoagulants versus vitamin k antagonists in patients with atrial fibrillation and bioprosthesis: a systematic review and meta-analysis

Abstract Background/Introduction The large randomized clinical trials published to date have shown that direct oral anticoagulants (DOACs) are as or more effective than vitamin K antagonists (VKAs) in the prevention of thromboembolic events in atrial fibrillation (AF) and generally show a better bleeding risk profile. However, patients with bioprosthetic valves have been underrepresented in RCTs. The aim of this study was to assess the safety and efficacy of DOAC in patients with AF and bioprosthetic valves through a systematic review and meta-analysis including recent evidence from comparative cohort studies and real-world results. Methods A systematic review of the scientific literature and a subsequent meta-analysis were carried out. We included RCTs or comparative observational studies, published from January 2017 to January 2022 comparing DOACs versus vitamin K antagonists in patients with AF or atrial flutter and bioprostheses. We collected data of all-cause mortality, major bleeding, and systemic embolism. The primary outcome of interest was all-cause mortality. Secondary outcomes were systemic embolism or stroke. The primary safety outcome was major bleeding. Results Our analysis included 12 studies, 4 RCTs and 8 observational studies that enrolled a total of 30.283 patients. All-cause mortality 6 observational and 3 RCT were combined. A 9% reduction was found for all-cause mortality in patients treated with DOACs (HR,0.91; P=.0068;95%CI,0.85–0.97;I2=8%). Stroke and systemic embolism 4 RCT and 8 observational studies were combined. No evidence showing a significant effect of DOAC therapy on risk reduction for stroke and embolism was obtained (HR, 0.87; P =.29; 95%CI, 0.67–1.14; I2=45%). Major bleeding The results of the 12 studies were combined. A robustness analysis was performed, and the ENVISAGE RCT was identified as atypical. We therefore proceeded to re-run the meta-analysis without this study’s results. The overall effect size was HR, 0.79 (P = .0001; 95%CI, 0.73-0.85; I2 = 0%), with a 21.1% reduction of major bleeding with DOAC therapy compared with VKA. The present study has several limitations. It has the inherent limitations of the studies included and the combination of findings from comparative observational cohort studies and ad hoc studies from RCTs, which entails a potential source of bias. Second, individual risks for each type of bioprosthesis were not studied. Finally, the four currently marketed DOACs were included in our meta-analysis, but their efficacy and safety were not evaluated separately. Conclusions Our study found that DOAC therapy is associated with a significant reduction of all-cause mortality with no significant increase in the risk of systemic embolism or stroke. This reduction could be attributed to a decrease in major bleeding. Our results therefore suggest that DOACs could be a safer alternative than VKAs in this group of patients.

Periprocedural management of direct oral anticoagulants in patients with atrial fibrillation and active cancer

BackgroundCancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer. ObjectivesTo describe patient characteristics, periprocedural management, and clinical outcomes in DOAC-treated patients with AF according to active cancer status. MethodsWe conducted descriptive and comparative analyses using data from the PAUSE study. Multivariable logistic regression was used to determine whether active cancer status was an independent risk factor for bleeding outcomes. Covariates were selected a priori based on biological rationale and preexisting knowledge. ResultsPatients with active cancer were older (P < .001), more likely to be thrombocytopenic (P = .026), have moderate renal dysfunction (P = .005), and more likely to receive low-dose DOAC therapy (P < .001). A greater proportion of patients with active cancer underwent a high-bleed-risk procedure (P < .001), with longer periprocedural DOAC-interruption intervals (P <.001) and lower preprocedural residual DOAC levels (P = .002). Active cancer was an independent predictor for surgical major bleeding (OR = 2.45; 95% CI, 1.08-5.14) after adjusting for study center, procedure category and bleed risk, thrombocytopenia, hypertension, and the use of a P2Y12 inhibitor. ConclusionsActive cancer status is associated with an increased risk of surgical major bleeding among DOAC-treated patients with AF undergoing interruption of anticoagulation for elective invasive procedures.

Abstract 19017: Peri-Operative Bridging Requirement for Patients Chronically Taking Direct Oral Anticoagulants (DOACS) or Vitamin-K Antagonists (VKA) Before Undergoing the Elective Procedure: A Systematic Review and Meta-Analysis

Introduction: Many patients undergo elective interventions/surgical procedures while being on direct oral anticoagulants (DOACs) or vitamin-K antagonists (VKA) chronically. There is limited data on peri-procedural management of DOACs in patients undergoing elective procedures. It is also unclear if there is any role of peri-procedural bridging in patients on chronic VKA therapy. We conducted this study to evaluate the efficacy and safety of DOACs (continued vs. interrupted)and VKAs (with vs. without bridging) among patients undergoing elective procedures. Methods: This systematic literature review was conducted according to PRISMA guidelines until 10 th June 2023. The following inclusion criteria were used: adults, chronic use of VKAs or DOACs, elective procedures, and clinical trials. Primary endpoints were major bleeding, stroke, MI, and VTE. A generic variance random effects model was used to estimate odds ratios using CMA III. Heterogeneity and quality of studies were quantified via I 2 statistic and GRADE score, respectively. Results: 14 clinical trials were included (n=15683). There was no difference in the risk of major bleeding (OR: 1.06, 95% CI: 0.65 -1.7, I2: 46%) or risk of stroke(OR: 1.10, 95% CI: 0.66 - 1.84, I2: 0%) whether DOACs were held or continued respectively. Among patients on VKA, there was no difference in risk of major bleeding in bridging vs. no bridging groups (OR: 2.02, 95% CI: 0.87 - 4.71, I2:75%). There was no difference in the rates of stroke (OR: 0.44, 95% CI: 0.12 -1.58, I2: 0%), MI (OR: 1.64, 95% CI: 0.76 - 3.53, I2: 0%), and VTE (OR: 1.26,95% CI: 0.31 - 5.01, I2: 0%). The quality of included studies was low to moderate. Conclusion: Patients undergoing elective procedures and chronically taking DOACs have a similar risk of major bleeding and stroke when DOACs are continued or interrupted peri procedurally. Similarly, among patients on VKA who were bridged or not bridged, there was no difference in risk of bleeding, stroke, MI or VTE.