Use Of Rivaroxaban Research Articles

Effect of tramadol and DOACs with special attention to dabigatran on concomitant use, on the risk of mayor bleeding using BIFAP database in Spain.

Tramadol, a weak opioid, inhibits the reuptake of serotonin, a key feature on vascular homeostasis. A suspected interaction exists between dabigatran and tramadol, which might trigger an excess on risk of bleeding however, there is a gap in knowledge on this topic. To estimate the effects of tramadol, dabigatran and concomitant use on the risk of hospitalized major bleeds (Gastrointestinal bleeding and intra-extracranial bleeds). Among a validated established cohort of new users of oral anticoagulants for non-valvular atrial fibrillation (NVAF) aged 18 years or older, we identified all hospitalized bleed episodes (GIB and extra/intracranial bleeds) within 2008-2015. A nested case-control analysis was conducted using conditional logistic regression. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated for dabigatran, tramadol, and concomitant use. Several sensitivity analyses were carried out. aORs (95%CIs) for current use of only dabigatran, only tramadol and concomitant users were 1.73 (1.37-2.18) and 1.38 (1.13-1.67) and 2.04 (0.74-5.67) compared with non-users of both drugs (>365 days). aORs for current continuers and non-continuer users of dabigatran were 1.36 (1.00-1.86) and 2.19 (1.61-2.98), respectively. For the latter, non-continuer users with a short duration of dabigatran cumulated the highest risk (3.36 [1.88-5.99]). There also was an increased risk with concomitant use of tramadol and rivaroxaban (2.24 [1.19-4.21]), or antagonist of vitamin K (1.30 [1.00-1.69]). There was a trend towards and increased risk of excess bleeds when using concomitantly with dabigatran. The effect decreases with a narrower definition of current use.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Antiphospholipid Syndrome: A Systematic Review and Meta-Analysis.

Due to a high risk of recurrent thromboembolism in patients with antiphospholipid syndrome (APS), long-term anticoagulation is recommended. For decades, vitamin K antagonists (VKAs) have been the gold standard for thromboprophylaxis in these patients. Due to the widespread use of direct oral anticoagulants (DOACs) in various thromboembolic conditions and their potential advantages compared to VKAs, several studies have been conducted to evaluate their safety and efficacy in APS.We performed a literature search using PubMed, Embase, and Cochrane databases for studies comparing DOACs to VKAs in patients with APS. Relative risk (RR) and the corresponding 95% confidence intervals (95% CI) were estimated for recurrent thromboembolic events, bleeding, and mortality.A total of 1437 patients pooled from 12 studies were analyzed. The risk of recurrent thrombosis, especially arterial thrombosis, doubled with DOACs compared to VKAs (RR 2.61, 95% CI 1.44-4.71; p=0.001). The risk further increased in patients with a triple-positive antiphospholipid antibody profile (RR 4.50, 95% CI 1.91-10.63; p=0.0006) and with the use of rivaroxaban (RR 1.95, 95% CI 1.10-3.45; p=0.02). The risk of major bleeding and mortality were not significantly different between the two arms. A trend favoring DOACs compared to VKAs was observed for all bleeding events. This meta-analysis comes in agreement with previous studies and supports the use of VKAs in APS. Our study revealed that VKAs remain the gold standard for the management of APS, especially triple-positive APS. DOACs, particularly rivaroxaban, are not as effective in preventing recurrent thromboembolism in high-risk APS patients. Further studies are needed to evaluate the role of DOACs apart from rivaroxaban with a focus on their efficacy in the management of isolated or double-positive APS.

Do Patients with Atrial Fibrillation and a History of Ischemic Stroke Overuse Reduced Doses of NOACs?-Results of the Polish Atrial Fibrillation (POL-AF) Registry.

Background: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). Methods: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. Results: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use—out of reduced dosage groups, p = 0.06). Conclusions: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.

Efficacy and safety evaluation of rivaroxaban vs. warfarin among non-valvular atrial fibrillation patients undergoing lower extremity revascularization.

IntroductionThe efficacy and safety of antithrombotic strategies remain uncertain in patients with atrial fibrillation undergoing lower-extremity revascularisation.Materials and methodsBetween January 2011 and November 2021, 319 patients with atrial fibrillation after lower-extremity revascularisation received rivaroxaban or warfarin treatment as anticoagulation regimens with different antiplatelet therapy strategies. The primary efficacy outcome was the composite of acute limb ischaemia, major amputation for vascular causes, myocardial infarction, ischaemic stroke, clinically driven target lesion revascularisation, and death from vascular causes. The safety outcomes were major bleeding events according to the International Society on Thrombosis and Haemostasis classification criteria.ResultsA total of 178 and 141 patients received rivaroxaban and warfarin treatments, respectively, after revascularisation with or without antiplatelet regimens. The incidence of the primary efficacy outcome at 36 months in the rivaroxaban group (44 patients, 24.7%) tended to be lower than that in the warfarin group (43 patients, 30.5%) (hazard ratio, 0.870; 95% confidence interval, 0.565–1.339; P = 0.527). The incidence of the secondary efficacy outcomes decreased in the rivaroxaban group (56 patients, 31.6%) compared with that in the warfarin group (61 patients, 43.2%). Major bleeding events occurred in three patients (1.7%) in the rivaroxaban group and five patients (3.5%) in the warfarin group; no significant difference in fatal or intracranial bleeding was observed between the groups.ConclusionThis study describes practical experience regarding the use of rivaroxaban and warfarin in patients with peripheral arterial disease complicated by non-valvular atrial fibrillation following endovascular intervention. The efficacy and safety outcomes do not differ significantly between rivaroxaban and warfarin.

Mitochondrial mitophagy protection combining rivaroxaban and aspirin in high glucose-exposed human coronary artery endothelial cell. An in vitro study.

PurposeCombination of Rivaroxaban plus Aspirin improved cardiovascular outcome in patients with stable cardiovascular disease. The aim was to determine if Rivaroxaban and acetylsalicylic acid alone or in combination may protect mitochondrial mitophagy in human coronary artery endothelial cells (HCAEC) exposed to D-glucose.MethodsHCAEC were incubated under different conditions: 5 mmol/L glucose D-glucose (control), 30 mmol/L D-Glucose with and without 50 nmol/L Rivaroxaban (Rivaroxaban), 0.33 mmol/L ASA (ASA) or Rivaroxaban (12.5 nmol/L)+ASA (0.33 mmol/L; (Riva+ASA).ResultsHCAEC incubated with D-glucose showed an increased Factor Xa expression. The mitochondrial content of Pink-1 and Parkin were significantly reduced in high glucose-incubated HCAEC compared to control. Rivaroxaban+ASA significantly increased the mitochondrial content of Pink-1 and Parkin, and the mitochondrial membrane potential compared to D-Glucose group. Both ASA alone and Riva+ASA reduced reactive oxygen species (ROS) and tissue factor production induced by high glucose exposure.ConclusionUnder high glucose condition combining Rivaroxaban+ASA increased the mitochondrial content of Pink-1 and Parkin, restored mitochondria membrane potential and reduced ROS and tissue factor expression in HCAEC. It suggests potential effects induced by dual use of Rivaroxaban and ASA on the coronary endothelium subjected to high glucose condition.

Comparison of Aspirin and Rivaroxaban Plus Aspirin in the Management of Stable Coronary Artery Disease or Peripheral Artery Disease: A Systematic Review of Randomized Controlled Trials.

IntroductionLow-dose aspirin or clopidogrel, statins, renin–angiotensin system inhibitors, and beta blockers are the cornerstone therapy for cardiovascular prevention in patients with coronary heart disease. Using only single-antiplatelet therapy for secondary prevention in patients with stable coronary artery disease (SCAD) and/or peripheral artery disease (PAD) has a significant risk of recurrent thrombotic complications.ObjectiveThis systematic review aimed to compare aspirin alone and its combination with rivaroxaban for secondary cardiovascular prevention in patients with SCAD and/or PAD.MethodsThe literature search was conducted on PubMed, ClinicalTrials.gov, Cochrane Library, and Google Scholar for articles published from November 2011 to September 2021. An advanced search strategy was used to retrieve relevant studies related to aspirin and/or rivaroxaban use for secondary cardiovascular prevention in patients with SCAD and/or PAD. Records identified from the databases were extracted using a data-abstraction format prepared in Microsoft Excel. Studies’ methodological quality was assessed using the Cochrane risk-of-bias tool for randomized trials. This systematic review is registered in PROSPERO (CRD42022306598) and was prepared based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.ResultsA total of five randomized controlled trials (RCTs) with 33,959 participants were included for final analysis. These studies showed that rivaroxaban with aspirin was more effective than the standard therapy of aspirin alone in the prevention of secondary cardiovascular events (major adverse cardiovascular events (MACEs) and/or major adverse limb events (MALEs), but the combination increased major bleeding.ConclusionThe combination of rivaroxaban with aspirin is more effective than aspirin alone in the prevention of both MACEs and MALEs in patients with stable CAD and/or PAD. However, the combination treatment is associated with increased of major bleeding. Therefore, the combination of rivaroxaban and aspirin is superior to monotherapy in the management of patients with a high risk of developing MACEs and MALEs.

The Likelihood of Wound Complications Following the Use of Rivaroxaban as a Thrombo-Prophylactic Agent in Patients Undergoing Spinal Canal Stenosis Surgery: A Case Series

Background: Wound complications are major morbidities after orthopedic surgery, and thrombo-prophylactic drugs may increase the likelihood of such complications. In this regard, our study has evaluated the possible effects of rivaroxaban on wound complication issues following spinal canal stenosis surgery.&#x0D; Methods: This prospective cohort study was conducted on 40 patients suffering from spinal canal stenosis secondary to degenerative lumbar spine changes. The eligible patients included those patients receiving rivaroxaban to prevent thrombo-emboli post-operatively. The patients were followed up for three months and assessed for postoperative wound-related complications.&#x0D; Results: None of the patients suffered vascular and thromboembolic complications. Regarding wound complications, these events are mostly limited to the first week post-operatively, including wound dehiscence in 5.0%, serosanguineous discharge in 25.0%, erythema in 35.0%, superficial infection in 10.0%, requiring surgical debridement in 5.0%, cellulitis in 10.0%, and wound induration in 30.0%. Deep infection or hematoma was not reported in our patients. Erythema and wound induration remained 10.0% and 15.0% within the second week, respectively. The hypertrophic scar was a delayed complication that appeared in 15.0% of patients within 1 to 3 months post-operatively.&#x0D; Conclusion: The main risk profiles related to wound complications, especially infections, were a history of hypertension (HTN), uncontrolled diabetes mellitus (DM), and renal insufficiency. The use of rivaroxaban may be accompanied by temporary and minor wound complications and not with potentially debilitating morbidity in patients undergoing spinal canal stenosis surgery. Therefore, its prescription as a safe thrombo-prophylactic drug in patients undergoing spinal canal stenosis surgery is confidently recommended.

Trends in post-discharge prophylactic anticoagulant use among stroke patients in the United States between 2006 and 2019

BackgroundStroke is an independent risk factor for venous thromboembolism (VTE). Although the risk of VTE persists after hospital discharge, information on the utilization of anticoagulants among stroke patients after discharge remains limited. ObjectiveTo evaluate changes in post-discharge thromboprophylaxis among stroke patients between 2006 and 2019. MethodsWe conducted a retrospective repeated cross-sectional analysis using a commercial healthcare insurance database in the United States. We included patients aged ≥ 18 years with incident stroke diagnosis and assessed prophylactic use of anticoagulants in the 30 days following hospital discharge including low-molecular-weight heparin (enoxaparin ≤40 mg/day, dalteparin ≤5000 IU/day), unfractionated heparin ≤5000 IU/ twice daily or 3 times a day, apixaban 2.5 mg twice daily, and rivaroxaban 10 mg/day. Patients with atrial fibrillation, VTE, mechanical heart valves, cancer, antiphospholipid antibody syndrome, and users of therapeutic doses of anticoagulants were excluded. We used the Cochrane-Armitage test to assess changes in the use of anticoagulants across the study period. ResultsThere was a small increase in the overall use of post-discharge prophylactic anticoagulants among stroke patients between 2006 and 2019 from 0.5% to 1.9%. The use of heparin decreased from 0.5% in 2006 to 0.3% in 2019 (P-value for trend = 0.001). In contrast, the use of apixaban or rivaroxaban increased from 0.1% in 2013 to 1.6% in 2019 (P-value for trend < 0.001). Apixaban was more commonly used than rivaroxaban. ConclusionsIn this population-based study of stroke patients, we found that post-discharge anticoagulant use remains low through 2019. Prophylactic use of heparin or rivaroxaban was relatively low but the use of apixaban increased over the study period. Further research is needed to determine if these agents are safe and effective for VTE prevention in stroke patients.

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy.

Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97–170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25–6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.

ST Yükselmeli Miyokard Enfarktüslü Hastalarda Fibrinolitik ile Birlikte Kullanılan Tikagrelorun Etkinliği ve Güvenliği

Objective: The effectiveness and safety of administration ticagrelor simultaneously with fibrinolytic in STEMI remains unclear. Our study aims to compare and evaluate ticagrelor and clopidogrel in STEMI patients treated with fibrinolytics&#x0D; Material and Methods: The study consisted of 180 STEMI patients over 18 age who were given fibrinolytic therapy and had no absolute contraindications for treatment. Ticagrelor was given to 94 patients and clopidogrel was given to 86 patients. Loading doses were given to patients concurrently with fibrinolysis, followed by maintenance doses. The primary outcome was six-month follow-up for all-cause mortality, major cardiovascular events, stroke, recurrent MI, target vessel revascularization, and major bleeding. The secondary outcome was to evaluate patients over 75 years of age, use of rivaroxaban, and major adverse events that will develop in patients with chronic kidney disease.&#x0D; &#x0D; Results: There was no significant difference between the groups in terms of in-hospital death, GFR values (0.05). Mortality was observed in 5 of 86 patients using clopidogrel and in 4 of 94 patients using ticagrelor. (Log-rank test, p:0.63 HR=0.72 (95%CI, 0.19-2.67)). The BARC type 3-5 bleeding in patients using ticagrelor and clopidogrel were statistically similar. (Log-rank test, p:0.77 HR=1.23 (95%CI, 0.31 - 4.79))&#x0D; Conclusions: In this study, we found the use of ticagrelor with fibrinolytic therapy was similar to clopidogrel in terms of effectiveness and safety.

Non-vitamin K antagonist oral anticoagulants (NOAC) in nonvalvular atrial fibrillation – in-group comparison

&#x0D; Atrial fibrillation (AF) is a major and widespread health problem. Its main and most threatening complication, ischemic stroke, is responsible for a great number of deaths and disability worldwide. This makes anticoagulation a priority in AF management. Non-vitamin K antagonist oral anticoagulants (NOAC) are currently the most effective and safe option for patients with nonvalvular atrial fibrillation. Rivaroxaban, apixaban, edoxaban and dabigatran are non-inferior to warfarin in terms of stroke and systemic embolism prevention. However, warfarin use is associated with higher rates of major bleedings than any NOAC. Different drugs and mechanism of action among NOACs may result in differences in terms of efficacy and safety between them. This review aims to assess these differences by summarizing data available in online databases and European Society of Cardiology guidelines. There are major studies comparing each of NOACs to warfarin, however there is only limited data comparing apixaban, rivaroxaban and dabigatran directly. Both direct and indirect comparisons suggest that apixaban, rivaroxaban and dabigatran use is associated with similar reduction of stroke and systemic embolism risk. In terms of safety, anticoagulation with apixaban results in lower major bleeding risk relative to dabigatran and rivaroxaban. &#x0D;

Neutrophil-to-Lymphocyte Ratio Predicts Restenosis After Drug-Coated Balloon Therapy for Femoropopliteal Artery Lesions: A Retrospective Study.

BackgroundPeripheral artery disease (PAD) is a common atherosclerotic vascular disease. The use of drug-coated balloon (DCB) for the treatment of femoropopliteal artery disease has gradually increased. A certain percentage of patients developed target lesion restenosis after DCB treatment of the femoral popliteal artery. The neutrophil-to-lymphocyte ratio (NLR) is closely related to the level of inflammatory activity and has predictive value for atherosclerotic vascular disease. This study aimed to analyze the relationship between NLR and 1-year restenosis after DCB for femoropopliteal artery disease.MethodsPatients with femoropopliteal artery disease who were treated with DCBs at our hospital from May 2016 to December 2020 were retrospectively included. Baseline data during the patient’s first hospital stay and data during follow-up were collected. Demographic data, laboratory test results, lesion examination results, and major adverse events during the follow-up period were collected. Logistic regression was used to analyze the factors associated with restenosis after DCB.ResultsA total of 117 patients were included. During 1-year follow-up, 19 cases (16.2%) of restenosis were detected. Five of these patients (4.3% of total included patients) were readmitted for symptomatic ischemia. No deaths or amputations occurred. Baseline NLR in patients with restenosis was higher than that in patients without restenosis (2.4 (2.1, 3.4) vs. 1.8 (1.3, 2.3), P < 0.001). Logistic univariate and multivariate analysis showed that baseline hs-CRP level (OR = 1.10, 95%CI: 1.05–1.34), lesion length (OR = 1.04, 95%CI: 1.02–1.27), use of rivaroxaban (OR = 1.08, 95%CI: 1.05–1.39), NLR (OR = 1.47, 95%CI: 1.13–2.48), LDL-C level (OR = 1.25, 95%CI: 1.05–1.52), and diabetes (OR = 1.25, 95%CI: 1.05–1.52) = 1.18, 95%CI: 1.06–1.66) were predictors of restenosis.ConclusionBaseline NLR before DCB can predict the risk of restenosis after surgery.

Combined use of rivaroxaban and aspirin causes fatal AEs

Combined use of rivaroxaban and aspirin causes fatal AEs

Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase

PurposeThe aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs.MethodsThe WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed.ResultsBy January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one.ConclusionsFatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network.

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.

MO638: Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Obesity, Type Two Diabetes, CKD

Abstract BACKGROUND AND AIMS We aimed to estimate the clinical characteristics and outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity, type two diabetes (T2D) and chronic kidney disease (CKD). METHOD A multicenter prospective cohort study, where consecutive eligible rivaroxaban or warfarin treated patients with NVAF concurrent obesity, T2D and CKD, were registered. Patients were also required to be ≥18 years of age, and have obesity, which was defined as BMI ≥30 kg/m2 diabetes and CKD. Patients were followed-up for clinical events over a mean period of 1 year. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, end-stage kidney disease, while secondary outcomes included those components separated. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. RESULTS A total of 194 (n = 103, rivaroxaban; n = 91, warfarin) matched pairs of NVAF patients with obesity, T2D and CKD who initiated treatment with rivaroxaban or warfarin were included. Prior to matching, rivaroxaban patients were younger than warfarin patients (mean age, 67.9 versus 69.2 years) and had lower mean scores for the QCI, CHA2DS2-VASc and HAS-BLED. In the intent-to-treat analysis, patients receiving rivaroxaban had a significant 19% reduction in the composite risk of stroke or SE compared with those receiving warfarin [HR 0.85 (95% CI 0.77–0.90)]. The risk of each component of the composite outcome was lower in the rivaroxaban cohort versus the warfarin cohort with significant differences for ischemic stroke and hemorrhagic stroke. The difference in SE was not statistically significant. Outcome rates were lower in the as-treated sensitivity analysis, with significant reductions in the composite outcome of stroke/SE risk observed for rivaroxaban versus warfarin [HR 0.70 (95% CI 0.61–0.80)]. Ischemic stroke and hemorrhagic stroke risks were also significantly lower with rivaroxaban versus warfarin in the as-treated sensitivity analysis. The risk of major bleeding was similar between the rivaroxaban cohort and the warfarin cohort [HR 0.91 (95% CI 0.79–1.06)]. CONCLUSION In NVAF patients with comorbidities of obesity, T2D and CKD, who initiated rivaroxaban had a significantly lower risk of stroke/SE compared with patients initiating warfarin. The risk of major bleeding was not significantly different between treatment groups. Patients receiving rivaroxaban had a significantly higher rate of adherence to treatment, supporting the use of rivaroxaban as an alternative to warfarin in NVAF patients with comorbidities of obesity, T2D and CKD.

Management of Venous Thromboembolism in Morbid Obesity With Rivaroxaban or Warfarin.

Rivaroxaban is a first-line option for the management of venous thromboembolism (VTE). However, limited data are available regarding its effectiveness in morbidly obese patients. To evaluate rates of thrombosis and bleeding in morbidly obese patients receiving rivaroxaban or warfarin for VTE. A multicenter, retrospective cohort study was conducted to compare rates of bleeding and thrombosis in patients receiving rivaroxaban versus warfarin for acute VTE. Patients were included if they were older than 18 years and had a body mass index (BMI) greater than 40 kg/m2 or weight greater than 120 kg. The primary effectiveness outcome was hazard of VTE recurrence; the primary safety outcome was hazard of major bleeding. Patients were followed for up to 12 months. A total of 1281 patients were identified for acute VTE and were included in this study with 487 patients receiving rivaroxaban and 785 receiving warfarin. The average cohort age was 57.6 ± 14.6 years, and the average weight was 136.4 ± 27.2 kg. After controlling for confounding factors, the use of rivaroxaban was not associated with an increased hazard of VTE events when compared with warfarin (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.42-1.08, P = 0.12) or major bleeding (HR = 1.29, 95% CI: 0.66-2.30, P = 0.52). No difference was observed in obese patients with weight >120 kg or BMI >40 kg/m2 receiving rivaroxaban or warfarin for VTE treatment in hazard of VTE or major bleeding. Either agent may be considered an appropriate treatment option in this population.

Rivaroxaban Induced Hallucinations: A Case Report

Hallucinations induced by rivaroxaban are not much described in literature. This case report describes the occurrence of a specific adverse event during rivaroxaban use in an elderly male who developed hallucinations few months after starting rivaroxaban. Other possible causes for these events were ruled out through comprehensive medical examination. Drug discontinuation led to resolution of adverse drug reaction. The mechanism involved in rivaroxaban-induced hallucinations is not known. The adverse event in our patient was possibly caused by rivaroxaban. Although there is still no strong evidence that can associate hallucinations to rivaroxaban use, and others unknown factors might be involved, this adverse event should be kept in mind when prescribing this drug to older patients.

Drug Use Evaluation of Direct Oral Anticoagulants (DOACs) in Patients With Advanced Cirrhosis.

Objectives: Low molecular weight heparin and vitamin K antagonists are commonly used in cirrhotic patients requiring anticoagulation. However, their monitoring with anti-factor Xa and international normalized ratio (INR) may not be reliable in cirrhosis. Direct oral anticoagulants (DOACs) do not need laboratory monitoring, making these agents a favorable alternative. However, apixaban and rivaroxaban have been avoided in advanced liver disease due to their metabolism in the liver. The purpose of this medication use evaluation was to assess the use of DOACs, specifically apixaban and rivaroxaban, in patients with cirrhosis.Methods: We performed a retrospective, single-center study. Inpatients who had a diagnosis of cirrhosis and received at least one dose of a DOAC (apixaban or rivaroxaban) from April 2016 through June 2020 at our hospital were included in the analysis. Data collected included the reason for admission, Child-Pugh classification, renal function, if this was a home medication or newly started as an inpatient medication, indication, and dosing. The clinical efficacy outcome (new venous thromboembolic event (VTE) or progression of old VTE), and clinical safety outcome (bleeding event) were analyzed.Results: 41 patients with cirrhosis were treated with apixaban or rivaroxaban. Based on the Child-Pugh classification, 29.3% (n=12/41) were placed on a DOAC outside of the FDA prescribing recommendations. In this subpopulation, 8.3% (n=1/12) patients had venous thromboembolism (VTE) and 16.6% (n=2/12) had bleeding events. Overall, 7.3% patients (n=3/41) had VTE and 4.8% (n=2/41) had bleeding events. In the Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial comparing the efficacy and safety profile of apixaban with enoxaparin/warfarin therapy in acute VTE, 2.3% of patients had VTE and 15% had bleeding events.Conclusion: Our study demonstrated that it may be possible to safely use DOACs in patients with advanced cirrhosis. Further studies are needed to evaluate the safety and efficacy of DOACs in this patient population, as our study was limited by the small sample size and its retrospective design.

DOACs and Atherosclerotic Cardiovascular Disease Management: Can We Find the Right Balance Between Efficacy and Harm.

The balance between efficacy and harm remains a challenge in the adoption of non-vitamin K antagonist direct oral anticoagulants (DOACs) for secondary atherosclerotic disease prevention. We provide a comprehensive review of the evidence for and against the addition of DOACs to the current management of atherosclerotic cardiovascular disease, including stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and percutaneous coronary interventions (PCI). The DOAC class exerts pleiotropic effects on atherosclerotic progression through coagulation and inflammatory pathways. In ACS, low-dose DOAC provides no added efficacy in the setting of dual antiplatelet therapy; however, full-dose DOAC increases bleeding. Efficacy-safety profile favor use of low-dose rivaroxaban in select stable CAD or PAD patients. Atrial fibrillation patients undergoing PCI resort to dual therapy with DOAC due to prohibitory bleeding with triple anti-thrombotic therapy. Evidence favors DOAC use in CAD and PAD; however, careful individual considerations must be undertaken.