Efficacy Of Factor Xa Inhibitors Research Articles

PB0953 An Updated Systematic Review and Meta-Analysis of the Safety and Efficacy of Factor Xa Inhibitors versus Low Molecular Weight Heparin Therapy for Treatment of Cancer Associated Venous Thromboembolism

PB0953 An Updated Systematic Review and Meta-Analysis of the Safety and Efficacy of Factor Xa Inhibitors versus Low Molecular Weight Heparin Therapy for Treatment of Cancer Associated Venous Thromboembolism

779: FACTOR XA INHIBITORS IN PATIENTS WITH ACUTE KIDNEY INJURY

Introduction: Data is lacking regarding the safety and efficacy of factor Xa inhibitors in patients with acute kidney injury (AKI). The goal of this study is to compare bleeding and thromboembolic events in patients receiving therapeutic doses of apixaban or rivaroxaban versus unfractionated heparin (UFH) in patients with AKI. Methods: This retrospective, observational study evaluated hospitalized adult patients who received therapeutic doses of either apixaban, rivaroxaban, or UFH for at least 24 hours in the setting of AKI as defined by AKIN criteria. Patients were excluded if they met any of the following criteria: non-FDA approved factor-Xa inhibitor indication; COVID admission; major bleeding or clinically relevant non-major bleeding (CRNMB) on admission, embolic event within 30 days of admission; coagulopathy; receipt of a contraindicated medication, or ESRD. Bleeding events were evaluated in accordance with International Society on Thrombosis and Hemostasis criteria. The primary outcome was defined as composite major and clinically relevant non-major bleeding events. Secondary outcomes included comparison of the individual components of the composite bleeding endpoint and thromboembolic events. Results: A total of 500 patients met inclusion criteria, with 250 patients included in the UFH group and factor Xa inhibitor group. AKIN Stage I was most prevalent in the overall study population; patients with AKIN stage III were more likely to be transitioned to UFH (p< 0.01). Surgical patients were more likely to be transitioned to UFH (p< 0.01). Patients transitioned to IV heparin were more likely to undergo a procedure (p< 0.01). After adjusting for confounding factors, patients who received a factor Xa inhibitor experienced a lower risk of composite major bleeding and CRNMB events as compared to UFH (OR: 0.57, 95% CI: 0.34-0.94; p = 0.03). This was driven by a decreased risk of CRNMB in the factor Xa inhibitor group (OR: 0.55, 95% CI: 0.33-0.91, p = 0.02). No significant differences in major bleeding or VTE were noted. Conclusions: Continuation of factor Xa inhibitor therapy in the setting of AKI was associated with a reduced incidence of bleeding events compared to patients transitioned to UFH in accordance with package insert recommendations.

Warfarin versus factor Xa inhibitors in the long-term treatment of cerebral venous sinus thrombosis a single-center retrospective analysis.

Long-term anticoagulation in the treatment of Cerebral Venous Sinus Thrombosis (CVST) has revolved around the use of warfarin. The relatively recent introduction of Direct Oral Anticoagulants (DOACs), such as Factor Xa inhibitors, in treating CVSTs promises to offer numerous patient benefits. We aimed to examine the efficacy of Factor Xa inhibitors in comparison to warfarin in the long-term treatment of CVSTs. A single-center retrospective analysis was conducted in which 49 eligible patients having presented with a first-time CVST were identified. Long-term anticoagulation was achieved with Warfarin (n = 23) or Factor Xa Inhibitors (n = 26; Apixaban or Rivaroxaban). Outcomes of interest were improvements in patient functional status, modified Ranking Scores (mRS), and radiographic improvement/resolution in sinus thromboses. Secondary comparisons included complication rates, particularly recurring venous thrombotic events. Patient mRS scores by 7-to-18-month follow-up all fell within the extremely favorable range of 0–1 regardless of the long-term anticoagulant (P-value = 0.3591). Proportion of patients with radiographic improvement/resolution of thrombosed sinuses trended towards being higher in the Factor Xa Inhibitor group at the <12-month period, 69.2%, compared to 33.3% with Warfarin (P-value = 0.0548). By the >12-month follow-up period, Warfarin and Factor Xa inhibitor groups had similar rates of radiographic sinus improvement – 76.9% versus 71.4%, respectively (P-value = 0.6298). No statistically significant differences were documented between groups regarding complications. Factor Xa inhibitors are equally as effective as Warfarin in the long-term treatment of CVSTs, whether it be restoring patient functional status, sinus thrombus burden reduction, or minimizing bleeding complications whilst preventing recurrent venous thrombosis.

Integrating Incompatible Assay Data Sets with Deep Preference Learning.

A large amount of bioactivity assay data is already accumulated in public databases, but the integration of these data sets for quantitative structure–activity relationship (QSAR) studies is not straightforward due to differences in experimental methods and settings. We present an efficient deep-learning-based approach called Deep Preference Data Integration (DPDI). For integrating outcome variables of different assay types, a surrogate variable is introduced, and a neural network is trained such that the total order induced by the surrogate variable is maximally consistent with given data sets. In a task of predicting efficacy of factor Xa inhibitors, DPDI successfully integrated 2959 molecules distributed in 129 assay data sets. In most of our experiments, data integration improved prediction accuracy strongly in interpolation and extrapolation tasks, indicating that DPDI is an effective tool for QSAR studies.

A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute venous thromboembolism

BackgroundThe factor Xa inhibitors have been widely used for the treatment and prevention of venous thromboembolism (VTE). However, the efficacy of factor Xa inhibitors in Japanese patients with VTE has not been well examined. In this study, we investigated the effect of the sequential use of two factor Xa inhibitors in patients with acute VTE. MethodsWe conducted an observational study of 87 consecutive patients diagnosed with VTE. As an initial treatment, we administered subcutaneous fondaparinux to the patients for 7–10 days, and then switched to oral rivaroxaban. The symptoms and findings were assessed after the initial treatment and after using rivaroxaban for 7–14 days. We evaluated the deep vein thrombosis (DVT) in the legs using our own scoring system [quantitative ultrasound thrombosis (QUT) score]. ResultsOf the 87 patients, 33% had symptoms, half had pulmonary embolism (PE), and 95% had DVT of the legs. Out of the 87 patients, VTE worsened during the administration of fondaparinux in 4 patients. All of them had experienced malignancy, and died within 6 months. Of two patients developing bleeding, one patient required a transfusion. Eventually, this strategy was effective in 80 patients and had no change in one. The D-dimer level was significantly reduced by fondaparinux (17.8μg/ml±16.0μg/ml vs. 8.3μg/ml±7.2μg/ml, p<0.0001), followed by rivaroxaban (8.3μg/ml±7.2μg/ml vs. 5.5μg/ml±4.9μg/ml, p<0.0001). Similarly, the QUT score was improved by fondaparinux (4.7±2.6 vs. 2.5±2.5, p<0.0001), and further reduced by rivaroxaban (2.5±2.5 vs. 1.9±1.8, p<0.0001). ConclusionsA treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute VTE in Japanese patients.

Safety and efficacy of oral factor-Xa inhibitors versus Vitamin K antagonist in patients with non-valvular atrial fibrillation: Meta-analysis of phase II and III randomized controlled trials

BackgroundAim of our study was to assess the safety and efficacy on factor-Xa inhibitors (FXIs) in patients with non-valvular atrial fibrillation (NVAF) as compared to Vitamin K antagonist (VKA). MethodsPhase II and III randomized controlled trials that reported clinical safety and efficacy of FXI in patients with NVAF were identified from MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through December 10, 2015. The primary safety outcome of our study was composite of stroke and systemic embolic event. Secondary outcomes studied were individual endpoints of primary safety outcome, major bleeding, clinically relevant non-major bleed (CRNMB), and all-cause mortality. ResultsWe included 11 RCTs with a total of 59,164 participants, of which 34,231 patients received oral FXI and 24,933 patients were on VKA with a mean follow-up of 369days. There was a significant reduction in primary outcome with FXI compared to VKA, 1,112 (3.4%) versus 816 (3.6%) events, respectively (OR 0.82; 95% CI 0.68–0.99). Use of FXI significantly reduced major bleeding events compared to VKA, OR 0.74, 95% CI 0.58–0.96, test for heterogeneity (I2=74%). Incidence of CRNMB was not different between FXI and VKA groups, OR 0.84, 95% CI 0.68–1.04. There was a significant reduction in all-cause mortality in FXI group compared to VKA group, OR 0.88, 95% CI 0.83–0.94 with no significant heterogeneity. ConclusionUse of FXI was associated with a significant reduction in major bleeding events and all-cause mortality without increased risk of stroke or SEE compared to VKA.

Factor Xa inhibitors for acute coronary syndromes

The activation of coagulation mechanisms plays a central role in the pathogenesis of acute coronary syndromes (ACS). Administration of unfractionated heparin (UFH) and low molecular weight heparins (LMWH), agents preventing the progression of thrombus formation, is a crucial therapeutic strategy. However, some limitations related to their use have recently stimulated the development of new synthetic agents. To evaluate the clinical efficacy and safety of factor Xa inhibitors for treatment of ACS compared to UFH or LMWH. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library (Issue 1, 2008), PubMed, EMBASE and LILACS as well as the publications from International Congresses and the reference lists of the selected studies in December 2008. We used randomized controlled trials (RCTs) comparing factor Xa inhibitors to UFH or LMWH during the course of ACS. Outcome measures included all-cause mortality, myocardial infarction, re-infarction, ischemia recurrence, and adverse events. The selection, quality assessment and data extraction of the included trials were done independently by two authors and disagreements were resolved by consensus. Data were analysed by the use of risk ratio (RR) with 95% confidence interval (CI), and the numbers needed to treat (NNT) were reported as needed. A total of four RCTs involving 27,976 subjects were included. Fondaparinux was the only factor Xa inhibitor identified in our included RCTs. Fondaparinux appeared to be related to a lower risk in all-cause mortality at 90 to 180 days (RR 0.89; 95% CI 0.81 to 0.97), especially in the group where enoxaparin (a LMWH) was the control drug. Fondaparinux was also associated with a lower risk in major and minor bleeding at 30 days compared to enoxaparin (RR 0.63, 95% CI 0.55 to 0.73; RR 0.34, 95% CI 0.28 to 0.43, respectively), but not when compared to UFHs (RR 1.41; 95% CI 0.49 to 4.10; RR 0.70, 95% CI 0.14 to 3.39 respectively). The therapeutic efficacy of factor Xa inhibitors in ACS seemed to be related to a reduced risk in all-cause mortality at 90 to 180 days, with a better safety profile than enoxaparin in terms of reduce incidence of major and minor bleeding.