Efficacy Of Direct Oral Anticoagulants Research Articles

The prevalence and safety of direct oral anticoagulants in patients with non-atrial fibrillation associated intra-cardiac thrombus

Abstract Background The standard of care in management of intra-cardiac thrombus has been the use of vitamin K antagonists (VKAs). The emergence and use of direct oral anticoagulants (DOACs) in other conditions has led to the consideration of their use in patients with intra-cardiac thrombus. Thus far, case-reports have provided the majority of data regarding the efficacy of DOACs in this population. Purpose The aim of this observational study was to investigate the safety and efficacy of DOACs in intracardiac thrombus not associated with atrial fibrillation, compared to the current standard of care, VKAs. Methods An observational study was conducted between 10 hospitals in our region. The study was conducted between 2013 and 2019 in patients with a diagnosis of intracardiac thrombus. All left and right, atrial and ventricular thrombi were included. Patients with atrial fibrillation were excluded. Patient information was collected from the hospital electronic record. The primary endpoints were clinically significant bleeding requiring transfusion and thromboembolic events, excluding myocardial infarction. Results 1153 patients had a diagnosis of intracardiac thrombus. 878 out of 1153 patients were discharged on warfarin and 275 were discharged on a DOAC. In the warfarin population 73 of 878 patients (8.3%) had clinically significant bleeding events compared to 21 of 275 patients (7.6%) in the DOAC population (p=0.801). The median ages were 60.5 and 58 respectively. The median time period to a bleeding event was 151 and 198 days respectively. In the warfarin population, 116 of 878 patients (13.2%) had thromboembolic disease versus 34 of 275 patients (12.4%) in the DOAC arm (p=0.759). The median ages were 62 and 62.5 respectively. The median time period to a thromboembolic event was 114 and 184 days respectively. In the warfarin arm, 3 patients had systemic thromboembolism and 113 patients had embolic strokes. In the DOAC arm, 2 patients had systemic thromboembolism, 32 patients had embolic strokes. Conclusion The data from this study suggests that DOACs may be a feasible alternative to warfarin in patients with intracardiac thrombus. There was no statistically significant difference in the rates of clinically significant bleeding or in incidence of thromboembolic disease. To our knowledge, this is the largest observational study to date on this topic. Randomized controlled trials are needed to fully establish the efficacy of DOACs in this patient population. Funding Acknowledgement Type of funding sources: None. Table 1

Effectiveness of direct oral anticoagulants in obese adults with atrial fibrillation: an overview examining the evidence from international systematic reviews and meta-analyses

Abstract Background Obesity may influence the pharmacology of direct oral anticoagulants (DOAC) that are recommended by all international guidelines for stroke prevention in adults with atrial fibrillation (AF). Purpose To evaluate the safety and efficacy of DOACs in obese adults with AF. Methods Medline, CINAHL, Scopus, Web of Science, Cochrane Database, Johanna Briggs Institute, Embase, Psych Info and ProQuest were searched till April 2020. Only systematic reviews with meta-analyses, that were published after 2005 and were in the English language were included. Articles were screened by title and abstract, followed by full text assessment using the Covidence systematic review software. Data was extracted using a standardised extraction tool. AMSTAR-2® and ROBIS® tools were used for quality and risk of bias assessment. The entire process was undertaken by two investigators at each stage of the study selection, appraisal, and data extraction. Disagreements were resolved through consensus discussion with a third arbitrary investigator. Statistical analyses were performed using the DerSimonian and Laird method for random effects. Meta-analysis was performed using only randomised controlled trials from eligible systematic reviews at both 12 months and across the entire trial. Primary outcomes assessed was stroke (ischemic or haemorrhagic) or systemic or pulmonary embolism. Secondary outcomes assessed included all-cause mortality, transient ischemic attack, myocardial infarction, major bleed, all cause-hospitalisation, and cardiovascular mortality. Results Of the 8162 articles screened, a total of five systematic reviews were included in this overview. There was disagreement within the published reviews on the effect of DOAC in obesity. Four of the five reviews were of either “low” or “critically low” quality, with inconsistencies in data extraction and appropriateness of the included studies and statistical methods used in analysis. Data from only the RE-LY, AVERROES and ENGAGE AF-TIMI 48 trials, were available for the meta-analysis, which did not find any significant difference between all BMI groups for all outcomes, at both time points. However, analysis of the different weight groups versus normal weight, highlighted non-significant differences between the different DOACs. Conclusion There was no difference between the BMI classes in any of the outcomes assessed. However, the non-significant trends that were seen, suggests individual superiority of DOACs may exist within the obese adult populations. There is a need for prospective trials to evaluate which DOACs are safe and efficacious in the obese class III adults and at which dose. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Australian Government Research Training Program (RTP) Heart Foundation of AustraliaNational Health and Medical Research Council (NHMRC)

Direct oral anti-coagulants in patients with atrial fibrillation and bioprosthetic valve: a meta-analysis of randomized controlled trials

Abstract Background Patients with atrial fibrillation (AF) and bioprosthetic valve (BPV) are at increased risk for thromboembolic events and require anticoagulation. However, management strategies for these patients have not yet been well addressed by randomized controlled trials (RCTs). For years, warfarin was the only available oral anticoagulant, but this changed with the introduction of the direct oral anticoagulants (DOACs). However, there is no clear consensus about indications for DOACs in these patients due to the lack of prospective trials. Purpose The objective of this meta-analysis is to show the efficacy of DOACs in AF patients with BPV in terms of composite cardiovascular outcomes. In addition, the study aims to show the safety of DOACs in terms of major bleeding. Methods A comprehensive literature search for randomized controlled trials (RCTs) was performed in MEDLINE, PubMed and Clinicaltrials.gov in human subjects done within 2010 to 2020. Results were pooled using fixed effects. The primary outcome was a composite cardiovascular outcome from all included studies, which include death, major bleeding and major adverse cardiac events (stroke, transient ischemic attack, valve thrombosis, myocardial infarction, systemic embolism, and hospitalization for heart failure). Secondary outcomes include all-cause stroke or systemic embolism, major bleeding, death from cardiovascular cause and all-cause death. Results Four RCTs were included in the meta-analysis. DOACs used were Apixaban, Dabigatran, Edoxaban and Rivaroxaban. In patients with AF and BPV, DOACs performed similarly with warfarin in terms of composite cardiovascular outcome (RR 1.01, 95% CI 0.86–1.19, P=0.88, I2=0%). On the other hand, DOACs performed better than warfarin in reduction of all cause stroke and systemic embolism (RR 0.48, 95% CI 0.27–0.87, P=0.01). There is non-statistically significant risk reduction for major bleeding (RR 0.81, 95% CI 0.56–1.17, P=0.26, I2=0%) and other secondary outcomes such as death from cardiovascular causes (RR 0.79, 95% CI 0.39–1.60, P=0.51, I2=0%) and all cause death (RR 0.94, 95% CI 0.55–1.62, P=0.71, I2=0%) showing similar outcomes with NOACs and warfarin. Conclusion DOACs compared with warfarin are similar in terms of composite cardiovascular outcome, major bleeding and death. However, DOACs performed better than warfarin in reducing all-cause stroke/systemic embolism and can be an alternative for oral anticoagulation in patients with AF and BPV. Funding Acknowledgement Type of funding sources: None. Forest plot for all-cause stroke or systemic embolism

Efficacy and safety of direct oral anticoagulants with diabetes and nonvalvular atrial fibrillation: a systematic review and meta-analysis

Abstract Background Diabetes Mellitus (DM) is an independent risk factor for stroke and atrial fibrillation (AF). Therefore, the risk/benefit profile of the direct oral anticoagulants (DOAC) is of clinical interest. Purpose To compare efficacy and safety outcomes of DOAC for nonvalvular AF in patients with DM versus without DM. Methods We systematically searched PubMed, Embase and Cochrane databases, in January 2020, for interventional studies comparing DOAC efficacy and safety in patients with AF and diabetes versus without diabetes. Results Four randomized clinical trials were included, providing a total of 63987 patients, 18860 with DM and 45127 without DM. In terms of efficacy, our meta-analysis revealed a similar rate of stroke/systemic embolism (pooled OR 1.02 [0.79, 1.31], P=0.87, I2=83%), stroke (pooled OR 1.98 [0.68, 1.40], P=0.90, I2=90%) and all-cause mortality (pooled OR 1.18 [0.97, 1.43], P=0.10, I2=87%), albeit with a significant heterogeneity. However, in direct factor Xa inhibitors sub analysis, diabetic patients had a lower trend of systemic embolism/stroke (pooled OR 0.90 [0.79, 1.02], P=0.09, I2=18%), significantly lower stroke rate (pooled OR 0.82 [0.73, 0.93], P<0.01, I2=0%), but a higher all-cause mortality (pooled OR 1.08 [1.00, 1.16], P<0.01, I2=0%). In terms of safety, the diabetic patients receiving DOAC had higher rates of major bleeding events (pooled OR 1.28 [1.14, 1.45], P<0.01, I2=50%), although with significant heterogeneity. Direct factor Xa inhibitors sub analysis also revealed a higher rate of major bleeding events (pooled OR 1.22 [1.08, 1.38], P<0.01, I2=24%), but a similar intracranial bleeding events (pooled OR 1.03 [0.86, 1.24], P=0.72, I2=0%). Conclusion Our pooled analysis suggests that diabetic patients on DOAC have an higher bleeding risk on DOAC, although with a superior embolic protection. Funding Acknowledgement Type of funding sources: None. Systemic Embolism/Stroke in DM vs. NonDM

Evaluation of direct oral anticoagulant use for cancer-associated venous thromboembolism (VTE) in lung cancer.

243 Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.

Safety and Efficacy of Direct Oral Anticoagulants in Patients With Moderate to Severe Cirrhosis.

Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred. DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

1690P A multicenter randomized phase II open label study to compare the safety and efficacy of direct oral anticoagulants versus subcutaneous dalteparin for cancer-associated venous thromboembolism in patients with advanced upper gastrointestinal, hepatobiliary and pancreatic cancer

The anticoagulation therapy in Cancer-associated venous thromboembolism (CA-VTE) is challenging especially in balancing the risks of recurrence of CA-VTE and bleeding during anticoagulation as cancer itself is a risk for both. Recently, direct oral anticoagulants (DOAC) has been recommended as treatment options equivalent to subcutaneous dalteparin. However, the issues about the bleeding risk of DOAC therapy have been continuously raised. This study evaluated the safety and efficacy of DOAC vs. subcutaneous dalteparin for CA-VTE in patients with advanced upper gastrointestinal (GI) tract, hepatobiliary, or pancreatic cancer.

Direct Oral Anticoagulants Versus Warfarin for Treatment of Thrombosis or Atrial Fibrillation in Patients With Cirrhosis: A Retrospective Cohort Study.

Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied. To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin. A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board. A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size. Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.

Direct Oral Anticoagulants Versus Warfarin in Left Ventricular Thrombus: A Systematic Review and Meta-Analysis.

There are conflicting results regarding the safety and efficacy of direct oral anticoagulants (DOACs) in the management of left ventricular thrombus (LVT) compared with the vitamin K antagonist warfarin. What is the safety and efficacy of DOACs in the management of LVT compared with warfarin? Randomized clinical trials and cohort studies in the MEDLINE and Cochrane databases from inception till April 4, 2021. The present analysis is a systematic review and meta-analysis. Desired outcomes were all-cause mortality, complete resolution of LVT, stroke and systemic emboli, and major bleeding. The risk ratio (RR) of the outcomes and 95% confidence intervals (CIs) were calculated using a random-effects modeling approach. Twelve studies with a total of 2322 patients were included. There was no difference between the 2 interventions in the resolution of LVT [RR 0.97 (CI 0.93-1.02)], stroke and systemic embolism [RR 0.95 (CI 0.63-1.45)], bleeding [RR 1.14 (CI 0.81-1.60)], and all-cause mortality [RR 0.99 (CI 0.67, 1.46)]. DOACs and warfarin have comparable safety and efficacy outcomes in the management of LVT.

Therapeutic efficacy of direct oral anticoagulants and vitamin K antagonists for left ventricular thrombus: Systematic review and meta-analysis.

BackgroundAlthough several meta-analyses have compared efficacies of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) for treatment of left ventricular thrombus (LVT), those meta-analyses included no single-arm studies.Methods and resultsPubMed, Scopus, and the Cochrane Library databases were searched for articles investigating thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, or all-cause death in LVT treated with VKAs or DOACs, and single-class meta-analyses were also included (PROSPERO database, CRD42021230849). Event rates were pooled using a random effects model. Meta-regression analysis was performed to explore factors that may influence outcomes. 2,612 patients from 23 articles were included (VKAs: 2,004, DOACs: 608). There were no significant differences between VKAs and DOACs in the frequency of thrombus resolution (VKAs: 0.75 [95% confidence interval; 0.67 to 0.81], DOACs: 0.75 [0.67 to 0.82]), stroke (VKAs: 0.06 [0.04 to 0.10], DOACs: 0.02 [0.01 to 0.01]), any thromboembolism (VKAs: 0.08 [0.05 to 0.13], DOACs: 0.03 [0.01 to 0.10]), major bleeding (VKAs: 0.06 [0.04 to 0.09], DOACs: 0.03 [0.01 to 0.06]), any bleeding (VKAs: 0.08 [0.05 to 0.12], DOACs: 0.08 [0.06 to 0.10]), and all-cause death (VKAs: 0.07 [0.04 to 0.13], DOACs: 0.09 [0.05 to 0.16]). Meta-regression analysis revealed that increased duration of follow-up was associated with lower-rates of stroke (estimate: -0.040, p = 0.0495) with VKAs, but not with DOACs. There was significant publication bias for thrombus resolution, stroke, any thromboembolism, any bleeding, and all-cause death.ConclusionsEfficacy and adverse outcomes of therapy with DOACs and VKAs do not differ. Randomized controlled trials are needed to determine the optimal anticoagulant strategy.

Safety and efficacy of Direct Oral Anticoagulants in cerebral venous thrombosis: A meta-analysis.

Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose to the risk of venous infarction and hemorrhage. Current guidelines recommend treating CVT with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) followed by an oral vitamin K antagonist (VKA) for 3-12months. Direct oral anticoagulants (DOACs) have already established benefit over warfarin as a long-term treatment of symptomatic venous thromboembolic disorder like deep vein thrombosis (DVT), and pulmonary embolism (PE) given its equal efficacy and better safety profile. The benefit of DOACs over warfarin as a long-term anticoagulation for CVT has likewise been extensively studied, yet it has not been approved as first-line therapy in the current practice. We therefore performed a systematic review and meta-analysis of relevant studies to generate robust evidence regarding the safety and efficacy of DOACs in CVT. This meta-analysis demonstrates that the use of DOACs in CVT has similar efficacy and safety compared to VKAs with better recanalization rate.

Adverse Events in Patients with Cancer Treated with Direct Oral Anticoagulants and Cancer Therapy

IntroductionFour direct oral anticoagulants (DOAC) have been approved for the treatment of venous thromboembolism VTE and prevention of stroke in patients with non-valvular atrial fibrillation (NVAF) in the USA: rivaroxaban, apixaban, edoxaban and dabigatran. Data regarding efficacy and safety of DOAC in the cancer population however are currently limited to very small cohorts in the large randomized trials for treatment of VTE in which many cancer patients did not meet eligibility requirements, or to retrospective studies and quality improvement initiatives. Despite major consensus guidelines recommending low molecular weight heparin (LMWH) as the preferred treatment for cancer-associated VTE, DOAC are commonly prescribed for cancer patients in both community and academic settings. Data on the safety and efficacy of DOAC in patients getting active cancer treatment are lacking. We aimed to characterize the use of DOAC in patients managed at an academic comprehensive cancer center, to examine the incidence of thrombotic and bleeding events among patients receiving active cancer therapy during the study period.MethodsFollowing IRB approval, a retrospective chart review was performed in patients treated at an academic comprehensive cancer center. Patients >18 years old who had a prescription written for a DOAC between June 2015 and December 2016 were identified. Patients were included if they were receiving DOAC for NVAF, acute VTE, and secondary prevention and had active cancer. Patients were assessed for baseline demographics, indications for anticoagulation, DOAC management strategies, arterial and venous thrombotic events and bleeding complications during treatment with DOAC. Descriptive statistics were used to analyze study outcomes.ResultsOf the 721 patients screened, 392 were patients with cancer of which 241 s were actively being treated with chemotherapy while on DOAC. The other 151 patients were not actively receiving treatment. VTE was the most common indication for DOAC use in 75% of cancer patients (n=297), followed by NVAF in20% (n=78). There were 15 patients with history of both NVAF and VTE, and 2 patients with TIA. Apixaban was used in 48% of patients; rivaroxaban in 47%; dabigatran in 4%, and edoxaban < 1%.Of the 392 evaluated cancer patients, 15 (3.83%) experienced thrombotic events with 11/15 new or recurrent VTE, 3/15 stroke, and 1/15 myocardial infarction while on DOAC. The VTE rate was strikingly higher in those patients receiving active cancer treatment at 4.15% compared to 0.66% in those not getting treatment. The rate of major bleeding and clinically overt bleeding was not different between the 2 groups and was approximately 4.5%. (table 1)ConclusionWe found in our retrospective analysis of DOAC use in cancer patients, that patients getting active cancer treatment had higher rates of primarily venous and arterial thrombotic events while treated with DOAC compared to those patients not getting active cancer treatment. The rate of VTE at 4.14% compares favorably with published rates for VTE recurrence for LMWH and VKA in randomized controlled trials and is roughly 7 times higher than the rate in our patients with cancer treated with DOAC but not getting active cancer treatment. Despite differences in rates of thrombotic events, the bleeding rates were the same, and also comparable to published rates, confirming the known increased risk of bleeding in cancer patients. While our results are promising, dedicated randomized controlled trials comparing DOAC to LMWH are required to truly determine the efficacy and safety of DOAC in cancer patients simultaneously receiving cancer treatment. [Display omitted] DisclosuresConnors:BMS: Consultancy, Other: Scientific Advisory Board; Pfizer/BMS -Alliance: Other: Independent review committe; Unum Therapeutics: Other: Data Safety Monitoring Board; boehringer Ingelheim: Other: Scientific Advisory Board.

Safety and Efficacy of Direct Oral Anticoagulants in Comparison to Low Molecular Weight Heparin in Hematological Malignancies

Introduction: The association between malignancies and venous thromboembolism (VTE) is a well established and significant cause of mortality in cancer patients. Compared to warfarin, low molecular weight heparin (LMWH) was found to be superior in preventing VTEs in the CLOT trial (Lee, et al. NEJM, 2003). Current guidelines recommend LMWH in patients with malignancies (Kearon, et al. Chest. 2016) however it is often difficult for patients to continue this long term given it is a subcutaneous injection that needs to be administered twice a day. Patients generally prefer direct oral anticoagulants (DOACs) due to ease of administration. When DOACs were compared to warfarin in non-cancer patients (RE-COVER, EINSTEIN, AMPLIFY, HOKUSAI-VTE trials), they had similar efficacy and safety profiles. There are limited studies looking at DOACs in malignancies, particularly in those with hematological malignancies who often present with cytopenias, making anticoagulation challenging. We performed a retrospective analysis to evaluate the efficacy and safety of DOACs compared to LMWH in patients with hematological malignancies.Methods: We performed a retrospective analysis of patients diagnosed with a hematological malignancy who were placed on either a DOAC or LMWH for a VTE or atrial fibrillation (AF) from January 2011 to May 2017. We classified leukemia as those with AML, ALL, or CML and categorized CLL with other lymphoma subtypes. We also included multiple myeloma, MGUS, MDS, and Waldenstrom's macroglobulinemia. We primarily assessed efficacy and safety of DOACs in comparison to LMWH. Efficacy was based on incidence of a new VTE while on anticoagulation, and safety was measured by incidence of a bleeding event while on anticoagulation. CTCAE grading was used for bleeding events. 168 patients on DOACs and 70 patients on LMWH were available for analysis.Results: Of the 168 patients on a DOAC, 108 (64%) were started for a VTE and 60 (36%) were started for AF. Of the 70 patients on LMWH, 67 (96%) were started for a VTE and 3 (4%) were started for AF. Median follow-up in the DOAC and LMWH group was 11 and 22 months, respectively. The groups were similar in median age, gender distribution, race, ethnicity, and malignancy types. Average weight between the DOAC and LMWH groups were 87 versus 90.5 kg, respectively. Estimated glomerular filtration rate was 81.2 mL/min/1.73m2 in the DOAC group and 86.6 mL/min/1.73m2 in the LMWH group. The majority of patients were diagnosed with either a lymphoma or leukemia (61.9% of patients with lymphoma/19.6% with a leukemia in the DOAC cohort, and 54.2% of patients with lymphoma/30% with leukemia in the LMWH cohort). The majority of patients had not yet achieved remission at time of DOAC/LMWH initiation (60.1% versus 58.6%, respectively). Apixaban was the most commonly prescribed DOAC (60.7%).Incidence of a new VTE was 11.3% (n=18) in the DOAC group versus 11.4% (n=8) in the LMWH group. Of those who experienced a new VTE in the DOAC group, the majority developed a new extremity DVT (72.2%, n=13). Only two patients developed a new pulmonary embolism (PE), both of which were non-life-threatening. Of the 8 patients who developed a VTE in the LMWH group, 4 developed a recurrent extremity DVT (50%), 2 developed a thrombus in the IJ (25%), 1 developed a portal vein thrombus (12.5%), and 1 developed a submassive PE (12.5%).The incidence of a bleeding complication on DOAC therapy was 10.7% (n=19) versus 11.4% (n=8) on LMWH therapy. Of the 19 bleeding events in the DOAC group, there were two intracranial bleeds, one grade 2 in the setting of a new stroke and the second considered Grade 4 after a mechanical fall. There were 6 gastrointestinal (GI) bleeding complications (3 grade 2, 3 grade 3). There were 3 grade 2 epistaxis and 3 grade 3 hemoptysis. There were two extremity hematomas and one abdominal hematoma after a trauma, all grade 3. Lastly, there were 2 grade 3 pericardial bleeding complications related to pacemaker exchanges.Of the 8 bleeding events in the LMWH group, there was one grade 4 intracranial bleed after a new stroke and one grade 4 upper GI bleed in the setting of esophageal varices. Otherwise there were 4 extremity hematomas, (3 grade 2, 1 grade 3), one grade 3 leg hematoma and one grade 3 hemoptysis.Conclusion: In those with hematological malignancies, DOACs appear to be non-inferior to the standard of care, LMWH, with similar efficacy and safety. [Display omitted] DisclosuresPortell:Infinity: Research Funding; TG-Therapeutics: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Roche/Genentech: Research Funding.

Safety and Efficacy of Apixaban and Rivaroxaban for the Treatment of Upper Extremity Deep Vein Thrombosis

Background: Patients with upper extremity deep vein thrombosis (UE-DVT) have unique risk factors determining their incidence and recurrence, and were not included in the large clinical trials leading to drug approval for rivaroxaban and apixaban. There is no published data examining the safety or efficacy of direct oral anticoagulants (DOACs) for UE-DVT.Objective: Using the Mayo Clinic registry, we evaluated the safety and effectiveness of rivaroxaban and apixaban for the treatment of UE-DVT.Methods: Consecutive patients treated with rivaroxaban or apixaban for UE-DVT, enrolled into Mayo Clinic Venous Thromboembolism (VTE) Registry between March 1, 2013 and April 30, 2017, were followed prospectively for safety and efficacy. Clinical, demographic and imaging data were collected from each participant at the time of study recruitment. Recurrent VTE, bleeding complications, and death were assessed at 3-month intervals. For subjects unable to return at 3 months, clinical status was assessed by written questionnaire. For unreturned questionnaires, a scripted phone interview was performed. The study was approved by Mayo Clinic Institutional Review Board.Results: Of the 875 subjects with venous thromboembolism in the registry, 37 had UE-DVT and least 3 months of follow up and 20 were treated with rivaroxaban or apixaban. Three subjects had additional sites of VTE other than UE-DVT (1 with pulmonary embolism, 1 with lower extremity deep vein thrombosis, and one with both). The mean age was 57.7 years (standard deviation [SD] 15.2), mean BMI was 30.8 (SD 9.2), and 12 (60.0%) were male (Table 1). Nine (45%) subjects had catheter-associated UE-DVT, 10 (50.0%) had a diagnosis of malignancy, 7 (35.0%) were receiving chemotherapy, 2 (10.0%) had recent surgery (<6 weeks), and 6 had a prior diagnosis of VTE. The mean time from diagnosis of UEDVT to initiation of treatment with rivaroxaban or apixaban was 1.7 days (SD 3.0). At 3 months of follow up, no subjects had recurrent VTE and no subjects had major or minor bleeding episodes. One patient died from underlying malignancy (32 days after starting rivaroxaban).Conclusion: In our ongoing registry of subjects with VTE at Mayo Clinic, treatment of UE-DVT with rivaroxaban or apixaban appears to be safe and effective. Further research and a larger sample size are needed to determine the safety and effectiveness of DOACs for UE-DVT relative to other anticoagulants and lower extremity DVT. [Display omitted] DisclosuresMcBane:Bristol Myers Squibb: Other: Research grant for cancer associated VTE.

Safety and efficacy of direct oral anticoagulants (DOACs) in very elderly patients (≥85 years old) with non-valvular atrial fibrillation.

Limited real-world data are available regarding the comparison about safety and efficacy of DOACs prescription in very elderly patients (≥85 years) with non-valvular atrial fibrillation (NVAF). Concern about the risk of bleeding with anticoagulation in very older patients still represents an important challenge for clinicians. The aim of this study was to evaluate the different prevalence of major bleeding and thromboembolic events between very elderly NVAF patients (≥85 years) compared to those non very elderly (<85 years). Single center multidisciplinary registry including NVAF patients treated with DOACs. Primary safety endpoint was 2-year rate of major bleeding. Primary efficacy endpoint was 2-year rate of thromboembolic events. Event-free survival curves among groups were compared using Cox-Mantel Test. 908 NVAF consecutive patients were included, of these, 805 patients were <85 years (89%) and 103 patients were very elderly patients with ≥85 years (11%). Compared to patients <85 years, those very elderly have higher CHA2DS2-VASc Score (P=0.001), higher rate of hypertension (P=0.001), diabetes mellitus (P=0.030), previous bleeding events (P<0.001), previous stroke/TIA/SE (P≤0.001), heart failure (P≤0.001), and lower creatinine clearance (P<0.001). In terms of safety endpoints (overall ISTH-major bleeding) no significative difference between two groups (P=0.952) were observed up to 2-year follow-up. Systemic thromboembolic event (primary efficacy endpoint) was significantly higher in patients with ≥85 years (P=0.027). The incidence of all-cause death was significantly higher in very elderly patients (P<0.001). This single center registry, showed that the use of DOACs in very elderly NVAF was safe and is a therapeutic option to be pursued for stroke prevention especially for those who are at high risk of ischemic events.

Current Opinion on the use of Direct Oral Anticoagulants for the Prophylaxis of Venous Thromboembolism among Medical Inpatients.

Venous thromboembolism (VTE) is a known cause of morbidity and mortality, especially among acutely ill medical patients. Although VTE prophylaxis is part of post-discharge clinical care in surgical patients, there is controversy regarding its use in acutely ill medical patients and the current guideline statements suggest against its routine use. Recent clinical trials (APEX, MAGELLAN and MARINER) compared the safety and efficacy of direct oral anticoagulants (including betrixaban and rivaroxaban) with the standard of the care, enoxaparin, to identify the risk–benefit tradeoff. In this review, we summarized the key findings from these trials and substudies and recent updates in society guidelines regarding VTE prevention. In addition, we discussed the potential barriers, cost-effectiveness, and COVID-19 with respect to the implementation of extended-duration or post-discharge usage of direct oral anticoagulants.

Safety and efficacy of direct oral anticoagulants (DOACs) vs low molecular weight heparin (LMWH) in malignancy induced venous thromboembolism-a systematic review and meta analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background- Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) have been proven to be more effective in the management of venous thromboembolism (MVTE). The efficacy and safety of LMWH or DOACs in treatment of recurrent or malignancy induced VTE is not studied in literature. Objective To compare the efficacy and safety of LMWH and DOACs in the management of malignancy induced VTE Methods- Electronic databases ( PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Dichotomous data was extracted for prevention of VTE and risk of major bleeding in patients taking either LMWH or DOACs. Unadjusted odds ratios (OR) were calculated from dichotomous data using Mantel Haenszel (M-H) random-effects with statistical significance to be considered if the confidence interval excludes 1 and p &amp;lt; 0.05. Results- Three studies with 2607 patients (DOACs n = 1301 ; LMWH n = 1306) were included in analysis. All the study population had active cancer of any kind diagnosed within the past 6 months. Average follow-up period for each trial was 6 months. Patients receiving DOACs have a lower odds of recurrence of MVTE as compared to LMWH( OR 1.56; 95% CI 1.17-2.09; P = 0.003, I2 = 0). There was no significant difference in major bleeding among patients receiving LMWH or DOACs (OR-0.71, 95%CI 0.46-1.10, P = 0.13, I2 = 22%) (Figure 1). We had no publication bias in our results (Egger’s regression p &amp;gt; 0.05). Conclusion- DOACs are superior to LMWH in prevention of MVTE and have similar major bleeding risk as that of LMWH. Abstract Figure. A)VTE Recurrence B)Major Bleeding events

Safety and efficacy of direct oral anticoagulants (DOACs) vs warfarin in patients with concurrent atrial fibrillation and bioprosthetic mitral or aortic valve replacement-a meta analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background- Bioprosthetic valve (BPV) implantation is preferred over mechanical valves for aortic and mitral valve replacement. BPV can have concurrent atrial fibrillation (AF). Primary advantage of BPV is the limited need of anticoagulation (AC) as compared to mechanical valves. However, recommendations for use of AC in BPV are not clear. Purpose We studied direct oral anticoagulants (DOACs) cardiovascular efficacy and safety in BPV as compared to Vitamin K antagonist (VKA, or warfarin). Methods- Electronic databases (PubMed, Embase, Scopus, Cochrane) were searched from inception to November 28th, 2020. Using a generic invariance weighted fixed effects model, Hazard ratios (HRs) and their 95% confidence intervals (CIs) from individual studies were converted to Log HRs and corresponding standard errors, which were then pooled. The primary outcome of interest was stroke or systemic embolisation (SSE), major bleeding and all-cause mortality. Results- A total of four studies with 1386 participants (DOACs n = 723 ; VKA n = 656) were included in analysis. Mean age was 63.7 and 62.4 years in the DOACs and VKA group respectively. Average follow-up period was 1 year and 4 months. DOACs were more efficacious than VKAs in stroke or thromboembolism prevention (HR 0.43, 95%CI 0.20-0.94; p = 0.03). There was no difference in efficacy of DOACs as compared to VKAs in terms of major bleeding (HR 0.60; 95% CI 0.34-1.39; p = 0.09) and all-cause mortality (HR 0.99; 95%CI 0.57-1.7; p = 0.97) (Figure 1). We had no publication bias in our results (Egger’s regression p &amp;gt; 0.05). Conclusion- DOACs have similar mortality, and major bleeding risks as that of VKA at a benefit of higher stroke/thromboembolism prevention in patients with concurrent BPV and AF. Abstract Figure. A)SSE B)Major Bleeding C)Mortality

Comparison of the Safety and Efficacy of Direct Oral Anticoagulants and Warfarin in Atrial Fibrillation or Venous Thromboembolism in Patients with Renal Impairment: Systematic Review, Meta-Analysis and Network Meta-Analysis.

Due to the high risk of ischemic and arterial or venous bleeding events in atrial fibrillation (AF) or venous thromboembolism (VTE) patients with renal impairment (RI), selection of appropriate anticoagulant regimen is important. Therefore, we systematically reviewed and compared the safety and effects of oral anticoagulants in AF and VTE patients with RI. Eligible articles were identified through a literature search in PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library for studies published between January 2008 and November 2020. Network meta-analysis was conducted with STATA 14.0 to analyze the effects and safety of each drug with regard to different levels of renal function. 15 studies including 82,931 patients (76,957 with AF and 5974 with VTE) were analyzed. Compared with those of warfarin, the risk ratios of effect and safety outcomes of apixaban were 0.70 (95% confidence interval [CI] 0.60-0.82) and 0.56 (95% CI 0.42-0.76) in AF patients and 0.33 (95% CI 0.19-0.59) and 0.95 (95% CI 0.68-1.34) in VTE patients. Apixaban had the first or second highest probability of being ranked first with respect to surface under the cumulative ranking curve (SUCRA) scores in the prevention of major bleeding events, while in the prevention of ischemic events, rivaroxaban showed a higher SUCRA score (0.78-0.92) in mild RI patients and dabigatran showed a higher SUCRA value (0.90-0.99) in moderate RI patients. In the systematic review and meta-analysis, for AF or VTE patients with RI, direct oral anticoagulants performed comparably to or better than warfarin with regard to safety and effects. The network meta-analysis indicated that for patients with mild RI, apixaban might be safer for patients with a lower risk of ischemic events, while rivaroxaban might be suitable for patients with a lower risk of bleeding events. For patients with moderate RI, apixaban could reduce the risk of ischemic events without increasing the risk of bleeding events. For AF patients with severe RI, apixaban, rivaroxaban, and warfarin showed a similar effect. These results might provide suggestions for clinical arterial and venous thrombosis prevention.

Effectiveness and Safety of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Weighing ≥ 120 Kilograms versus 60-120 Kilograms.

Direct oral anticoagulants (DOACs) have become favorable choices for anticoagulation due to their fixed-dose schedule, limited need for monitoring, and non-inferiority or superiority to warfarin. DOACs are currently not recommended in patients with a body weight ≥120 kg or body mass index ≥40 kg/m2 due to limited data regarding safety and efficacy. The aim of this study was to compare the safety and efficacy of DOACs in patients with nonvalvular atrial fibrillation (NVAF) and weighing ≥120 kg with those weighing <120 kg. A single-center, retrospective study was conducted in patients weighing ≥120 kg who received either apixaban, dabigatran, or rivaroxaban for stroke risk reduction in NVAF, and matched to patients who weighed <120kg. The primary outcome was the incidence of stroke, deep vein thrombosis, pulmonary embolism, or myocardial infarction, while the safety outcome was the incidence of major or clinically relevant non-major bleeding based on the International Society on Thrombosis and Haemostasis (ISTH) definitions. A total of 318 patients weighing ≥120 kg with NVAF and meeting the inclusion criteria were evaluated and matched with 318 patients weighing <120 kg. The primary outcome occurred in 2.5% of patients in the ≥120 kg group and in 3.1% of patients in the <120 kg group (p=0.632). The safety outcome occurred in 5.3% and 6.6% of patients in these respective groups (p=0.503). Apixaban, dabigatran, or rivaroxaban may be well-tolerated and effective anticoagulant options in patients with NVAF weighing ≥120 kg.