Rivaroxaban Patients Research Articles

To Compare the Efficacy of Rivaroxaban with Nicoumolone in the Management of Patients with Intraventricular Thrombus

Objectives: Left ventricular thrombus (LVT) poses serious risks, including stroke and systemic embolism. Anticoagulant therapy is crucial, yet uncertainty persists in optimal management. This study aims to compare nicoumalone and rivaroxaban for LVT, assessing efficacy, safety, and monitoring considerations to inform clinical decision-making. Materials and Methods: This prospective and open-label trial compared rivaroxaban and nicoumalone efficacy in managing LVT over a 1-year period (September 2021–September 2022). Thirty-one patients from Government General Hospital, Guntur, meeting inclusion criteria were enrolled. Data were collected through interviews and echocardiography. Primary outcomes included thrombus resolution and recurrence; secondary outcomes encompassed adverse effects such as bleeding and stroke. Standard dosing and monitoring protocols were followed for each intervention. Results: In this study, both nicoumalone and rivaroxaban groups exhibited a reduction in LVT size over time, although not statistically significant (P > 0.05). Complete resolution was achieved in 70.0% of nicoumalone patients and 81.8% of rivaroxaban patients, with no significant difference (P = 0.472). However, rivaroxaban group patients achieved complete resolution significantly faster (176.67 ± 43.589 days) compared to nicoumalone group patients (271.67 ± 115.24 days) (P = 0.028). Notably, one nicoumalone patient experienced LVT recurrence post-anticoagulation cessation. Conclusion: Rivaroxaban was discovered to be non-inferior to nicoumolone in terms of efficacy and safety in patients with LVT.

Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study.

Studies on the use of direct oral anticoagulants (DOACs) for preventing venous thromboembolism (VTE) in hospitalized cancer patients are lacking. Therefore, we conducted a multicenter retrospective cohort study to evaluate the efficacy and safety of DOACs versus low-molecular-weight heparin (LMWH) for the primary prevention of VTE in hospitalized cancer patients. Clinical outcomes included thrombosis, VTE, other thrombosis, all bleeding, major bleeding, nonmajor bleeding, and all-cause death. A 1:1 cohort of rivaroxaban and LMWH patients was created by propensity score matching. A total of 2,385 cancer patients were included in this study. During the 3-month follow-up period, 129 (5.4%) thrombosis events occurred, 63 (2.7%) of which were VTEs and 66 (2.8%) of which were other thrombosis events. All bleeding occurred in 163 (6.8%) patients, 68 (2.9%) had major bleeding, and 95 (4.0%) had nonmajor bleeding. All-cause deaths occurred in 113 (4.7%) patients. After adjusting for various confounders, the incidence of thrombosis and other thromboses was significantly lower in the rivaroxaban group than in the LMWH group [OR 0.543, 95% CI (0.343-0.859), p = 0.009; OR 0.461, 95% CI (0.241-0.883), p = 0.020]. There were no significant differences in incidence of VTE, total bleeding, major bleeding, nonmajor bleeding, or all-cause death. In oncology patients receiving thromboprophylaxis, rivaroxaban has a lower incidence of thrombosis and other thrombosis and a similar incidence of VTE as LMWH and does not increase the risk of bleeding. Rivaroxaban may be an attractive alternative to LMWH for preventing VTE in hospitalized cancer patients.

Rivaroxaban plus aspirin vs. dual antiplatelet therapy in endovascular treatment in peripheral artery disease and analysis of medication utilization of different lesioned vascular regions.

In the management of Peripheral Arterial Disease (PAD), the administration of anticoagulant or antiplatelet agents is imperative. The use of Dual Antiplatelet Therapy (DAPT) in conjunction with rivaroxaban has shown potential in mitigating adverse outcomes. Given the heterogeneity in the pathology of lower limb arteries, there is a compelling case for individualized treatment strategies. In a single-center retrospective study on pharmacotherapy for peripheral artery disease, patients were treated with either aspirin combined with rivaroxaban or aspirin coupled with clopidogrel. The primary efficacy outcome encompassed a composite of increases in the Rutherford classification, acute limb ischemia, amputations due to vascular causes, target lesion revascularization, myocardial infarction, ischemic stroke, and cardiovascular death. The primary safety outcome was major bleeding, as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria; meanwhile, major bleeding as categorized by the International Society on Thrombosis and Haemostasis (ISTH) served as a secondary safety outcome. The study differentiated between two subgroups: patients with only above-the-knee and below-the-knee arterial lesions. From January 2016 to December 2021, 455 patients received either clopidogrel plus aspirin or rivaroxaban plus aspirin following endovascular treatment (EVT). The rivaroxaban group (n = 220) exhibited a lower incidence of primary efficacy outcomes [49.1% vs. 60.4%, hazard ratio (HR) 0.77, P = 0.006] but had more TIMI major bleeding events (5.9% vs. 2.1%, HR 2.6, P = 0.04). ISTH major bleeding events did not show a significant difference, though a higher percentage of rivaroxaban patients discontinued medication due to bleeding (10% vs. 4.7%, HR 2.2, P = 0.03). In the above-the-knee arterial disease subgroup, the rivaroxaban group demonstrated a lower incidence of primary efficacy outcomes (28.2% vs. 45.2%, HR 0.55, P = 0.02). In the below-the-knee arterial disease subgroup, no significant difference was observed in the occurrence of primary efficacy events between the two groups (58.7% vs. 64.8%, HR 0.76, P = 0.14). Rivaroxaban plus aspirin improved outcomes compared to DAPT in patients with lower extremity artery disease. Similar findings were observed in the above-the-knee artery lesion-only group. However, in the below-the-knee artery lesion-only group, rivaroxaban plus aspirin did not surpass DAPT in efficacy. Regarding safety, rivaroxaban plus aspirin exhibited higher bleeding risks and more frequent treatment discontinuation than aspirin combined with clopidogrel.

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60–1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71–1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Effectiveness and Safety of Rivaroxaban and Low Molecular Weight Heparin in Cancer-Associated Venous Thromboembolism

Direct-acting oral anticoagulants (DOACs) are alternatives to low molecular weight heparin (LMWH) in most cancer-associated thrombosis (CAT) patients. This study sought to compare the effectiveness and safety of rivaroxaban and LMWH for venous thromboembolism (VTE) treatment in patients with an active cancer type not associated with a high risk of DOAC bleeding. An analysis of electronic health records from January 2012 to December 2020 was performed. Patients were adults, had active cancer, experienced an index CAT event, and were treated with rivaroxaban or LMWH. Patients with cancers with an established high risk of bleeding on DOACs were excluded. Baseline covariates were balanced using propensity score-overlap weighting. HRs with 95% CIs were calculated. We identified 3,708 CAT patients treated with rivaroxaban (29.5%) or LMWH (70.5%). The median (25th-75th percentiles) time on anticoagulation was 180 (69-365) and 96 (40-336) days for rivaroxaban and LMWH patients. At 3months, rivaroxaban was associated with a 31% reduced risk of recurrent VTE vs LMWH (4.2% vs 6.1%; HR: 0.69; 95% CI: 0.51-0.92). No difference in bleeding-related hospitalizations or all-cause mortality was observed (HR: 0.79; 95% CI: 0.55-1.13 and HR: 1.07; 95% CI: 0.85-1.35, respectively). Rivaroxaban reduced the recurrent VTE risk (HR: 0.74; 95% CI: 0.57-0.97) but not bleeding-related hospitalizations or all-cause mortality at 6months. At 12months, no difference was observed between cohorts for any of the previously mentioned outcomes. Among active cancer patients experiencing VTE and not at high risk of bleeding on DOACs, rivaroxaban was associated with a reduced risk of recurrent VTE versus LMWHs at 3 and 6months but not 12months. (Observational Study in Cancer-Associated Thrombosis for Rivaroxaban-United States Cohort [OSCAR-US]; NCT04979780).

Renal outcomes of rivaroxaban compared with warfarin in Asian patients with nonvalvular atrial fibrillation: A nationwide population-based cohort study.

Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians. To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients. Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population. We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA2DS2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m2, rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001). Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

Thrombin generation in real life bleeding patients on oral anticoagulants reversed (or not) with (activated) prothrombin complex concentrate

BackgroundBleeding during oral anticoagulant therapy is currently codified by expert guidelines. Monitoring of coagulation during bleeding events is challenging. Our study sought to assess thrombin generation assay (TGA) in direct oral anticoagulant-treated patients without bleeding (WB), bleeding without reversal therapy (BR-), and bleeding with reversal therapy (BR+). MethodsWe conducted a prospective, monocentric study from June 2015 to June 2018. For all bleeding groups, TGA was evaluated using platelet-poor plasma collected upon arrival at emergency (T0), and 30 min (T1), 6 h (T2) and 24 h (T3) after reversal therapy (if indicated) following activation by tissue factor 5 pM and phospholipids. ResultsOverall, 292 patients participated, including 91 BR+, 94 BR-, and 107 WB patients. At T0, vitamin K antagonist reversed (VKA-BR+) patients experienced a significant decrease in TGA parameters (ETP and peak) compared with VKA without bleeding (VKA-WB). Compared with healthy controls, VKA-BR+ patients reversed by four-factor prothrombin complex concentrate (4F-PCC) displayed comparable TGA ‘s ETP and peak at T1, T2, and T3, whereas direct anti-Xa BR+ patients reversed by 4F-PCC or activated prothrombin complex concentrate (aPCC) reached thrombin generation parameters that exceeded normal range at T2 and T3. ConclusionsIn VKA-treated patients reversed by 4F-PCC, TGA parameters were normalized, whereas in rivaroxaban or apixaban-treated patients reversed by 4F-PCC or aPCC, TGA parameters exceeded normal range. Further studies are needed to compare the efficacy and safety of a different dose of reversal therapy and the impact on coagulation parameters.

Practical Nomogram Predicting Apixaban or Rivaroxaban Concentrations from Low-Molecular-Weight Heparin Anti-Xa Values: Special Interest in Acute Ischemic Stroke Patients

In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated anti-Xa thresholds up to 50 ng/mL have been proposed. However, specific DOAC assays are not widely available contrarily to low-molecularweight heparin (LMWH) anti-Xa activity. We developed and validated a nomogram for predicting apixaban and rivaroxaban concentrations based on LMWH anti-Xa assay. Our prospective study included apixaban (n=325) and rivaroxaban (n=276) patients. On the same sample, we systematically measured specific DOAC concentration and LMWH anti-Xa activity, using STA®-Liquid-Anti-Xa (Stago) and specific DOAC- or LMWH-calibrators, respectively. The nomogram was built using quantifiable values for both assays on the derivation cohorts with a log-linear regression model. Model performances including sensitivity, specificity, and true positive rate for different thresholds were checked on the validation cohorts. The models built from the derivation cohorts predicted that values <30 ng/mL and <50 ng/ mL DOAC thresholds corresponded to LMWH-anti-Xa values <0.10 IU/mL and <0.64 IU/mL for apixaban; <0.10 IU/mL and <0.71 IU/mL for rivaroxaban. The model accurately predicted apixaban/ rivaroxaban concentrations in the validation cohort. This easy-to-use nomogram, developed with our reagent, allowed accurately predicting DOAC concentrations based on LMWH-anti-Xa results in emergency situations such as AIS when drug-specific assessments are not rapidly available. Using DOAC <50 ng/mL equivalent threshold, instead of the fixed LMWH <0.5 IU/mL one, would allow proposing thrombolysis to more patients.

Antithrombotic and proton pump inhibitor co-therapy in patients with atrial fibrillation and stable coronary disease: a post hoc analysis of the AFIRE trial

Abstract Background Among patients with atrial fibrillation (AF) and stable coronary artery disease, bleeding events increased the cardiovascular events and mortality. We aimed to evaluate the effect of proton pump inhibitor (PPI) on the risk of bleeding events in these patients. Methods In the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease), patients with non-valvular AF and coronary artery disease were recruited and randomized to receive the rivaroxaban monotherapy or combination therapy with rivaroxaban plus antiplatelet drug. The present sub-analysis evaluated the risks of any bleeding events. Results Among 2,225 patients, 1,357 (61.3%) were receiving a PPI at baseline. During follow-up, 384 bleeding events were occurred, and incidence of bleeding events were significantly lower in patients with PPI compared with those without PPI (p=0.03). Among combination therapy with rivaroxaban plus antiplatelet, effect of PPI for cumulative incidence of bleeding events were significantly different between groups (p=0.01), however, these differences were not shown among rivaroxaban monotherapy patients (p=0.50, Figure 1). Multivariate Cox hazard analysis showed that PPI use had significantly lower risk of bleeding events (hazard risk 0.79, 95% confidence interval 0.64–0.97, p=0.03). In addition to PPI, male, heart failure and combination therapy with rivaroxaban plus antiplatelet drug were independent predictors of bleeding events. Conclusions PPI use was significantly associated with lower risk of bleeding events among patients with AF and stable coronary artery disease. Especially, for patients at high bleeding risk, such as receiving both anticoagulant and antiplatelet drugs, PPI is useful to reduce bleeding events. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The Japan Cardiovascular Foundation through a contract with Bayer Yakuhin.

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.

Study on the Relationship between Rivaroxaban and Factor Xa Activity in Blood Based on HPLC-MS/MS

The aim of the study was to investigate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivaroxaban and evaluate the correlation between plasma concentration and anti-Xa activity in patients using oral rivaroxaban. In this study, the plasma concentration of rivaroxaban and anti-Xa factor activities was determined in 125 patients, and the relationship between the two variables was analysed by SPSS 21.0 software. The results showed that the plasma concentrations of oral rivaroxaban patients were significantly correlated with the activity of the anti-Xa factor (Spearman's r = 0.990, P < 0.05). The plasma concentrations of rivaroxaban are a potentially useful monitoring indicator to assess the patient's bleeding risk if testing for plasma anti-Xa activity is not available.

Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran

BackgroundBleeding safety in relation to use of systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is insufficiently explored, despite clinical relevance and several reports suggesting associations. MethodsUsing nationwide Danish registers, we identified patients with atrial fibrillation initiated on apixaban, rivaroxaban, or dabigatran from 2012-2018. We investigated associations between bleeding incidents and systemic fluconazole or topical azole treatment using a case-crossover design with 30-day exposure windows and reported odds ratios (OR) with 95% confidence intervals (CI). ResultsWe included 32,340 (36%), 32,409 (36%), and 24,940 (28%) patients initiated on apixaban, rivaroxaban, and dabigatran, respectively. Patients on apixaban were older (median age: 77 years; interquartile range [IQR] 70-84) compared with rivaroxaban users (median age: 75 years; IQR 68-82) and patients on dabigatran (median age: 73 years; IQR 66-80). Apixaban users had a significantly increased risk of bleeding following exposure to systemic fluconazole: odds ratio (OR) 3.5; 95% confidence interval (CI), 1.4-10.6. No increased risk was found among rivaroxaban and dabigatran users: ORs of 0.9 (95% CI, 0.2-3.0) and 1.7 (95% CI, 0.5-5.6), respectively. As to bleeding risk pertaining to topical azole exposure among apixaban, rivaroxaban, and dabigatran users, no association was found, with corresponding ORs of 0.8 (95% CI, 0.5-1.3); 1.3 (95% CI, 0.9-2.1); and 1.2 (95% CI 0.8-1.8), respectively. ConclusionIn patients with atrial fibrillation on either apixaban, rivaroxaban, or dabigatran, an association between an elevated bleeding risk and use of systemic fluconazole was found among patients on apixaban. We found no increased risk of bleeding following co-exposure to topical azoles.

Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants versus warfarin

Abstract Background Clinical trials and real-world database studies have shown the benefits of non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin; however, measures of functional outcomes are critical in evaluating a patient's quality of life. Previous measures of time spent out of hospital in a home setting and time spent receiving disease-related care among non-valvular atrial fibrillation (NVAF) patients are lacking in the current literature. Purpose This analysis was based on the previously published ARISTOPHANES study, and used multiple data sources to evaluate the amount of time spent at a patient's home among NVAF patients who were prescribed NOACs versus warfarin. Methods This retrospective observational study used US data from CMS Medicare and four commercial databases to select adult NVAF patients who initiated apixaban, dabigatran, rivaroxaban, or warfarin (01JAN2013–30SEP2015). Time at home and time at home without external AF-related care were measured during the 180 days after the index date (OAC prescription). Time at home was defined as days from index date without any of the following: an inpatient, skilled nursing facility or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days away from home and days with a claim for bleeding, stroke/systemic embolism, AF, or an INR test. Each day a claim was observed was counted as one day. In each database, three 1:1 NOAC-warfarin propensity-score-matched (PSM) cohorts were created before pooling the results. After PSM, a subgroup of patients who were alive and had ≥180 days of follow-up was created. Poisson regression was conducted in each NOAC-warfarin matched cohort to compare time at home and time at home without external AF-related care. Results After matching, a total of 100,977 apixaban-warfarin, 36,990 dabigatran-warfarin, and 125,068 rivaroxaban-warfarin patient pairs were selected. Of those patients, 38–46% had 180 days of follow-up available. Across treatment cohorts, approximately 75% of patients were at home for the 180-day follow-up. Apixaban, dabigatran, and rivaroxaban patients had 1.3, 0.9, and 0.8 more days at home, respectively, compared to warfarin patients. Patients treated with apixaban had 13.4 more days at home without AF-related care compared to warfarin, while dabigatran and rivaroxaban had 11.6 and 11.7 more days at home without AF-related care compared to warfarin. A greater proportion of warfarin patients than NOAC patients had an INR test (81–82% vs 14–21%), and days with INR testing were the main driver for external AF-related care for warfarin patients. Conclusion Among NVAF patients treated with OACs, NOACs were associated with a longer time at home and time at home without external AF-related care compared to warfarin. These results can help inform healthcare providers and patients regarding the impact of NOAC treatment in NVAF patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

Time at home among nonvalvular atrial fibrillation patients treated with non-vitamin K antagonist oral anticoagulants: an ARISTOPHANES analysis

Abstract Background Patient-centered outcomes, such as home time, are becoming increasingly important quality-of-life measures. There are limited data on the impact of oral anticoagulants (OACs) on home time among patients with non-valvular atrial fibrillation. Purpose This analysis, based on the previously published ARISTOPHANES study, used five US insurance claims databases (CMS Medicare and four commercial databases) to compare home time among NVAF patients who were prescribed non-vitamin K antagonist OACs (NOACs). Methods Adult NVAF patients who were newly prescribed apixaban, dabigatran, or rivaroxaban (01JAN2013–30SEP2015) were selected. Time at home was calculated as the number of days from the index date (NOAC prescription) without any of the following: an inpatient, skilled nursing facility (SNF) or nursing facility, hospice, or inpatient rehabilitation facility admission. Time at home and without external AF-related care was defined as days from index date without any events from the home time endpoint or any days with a claim for bleeding, stroke/systemic embolism (S/SE), AF, or an INR test. Time at home and without external AF-related care were measured during the 180 days of follow-up; patients were required to have been alive and have 180 days of follow-up post index. In each database, three 1:1 NOAC-NOAC propensity-score-matched (PSM) cohorts were created before combining the databases. For each NOAC-NOAC matched cohort, Poisson regression was conducted to compare time at home and time at home without external AF-related care. Results After PSM, 37,314 apixaban-dabigatran, 107,236 apixaban-rivaroxaban, and 37,693 rivaroxaban-dabigatran patient pairs were created of which 37–44% had 180 days of follow-up available. Across the NOAC cohorts, approximately 21–25% of patients had an admission to a hospital, SNF, nursing facility, rehabilitation center, or hospice during the 180-day follow-up. The time at home was generally consistent between the NOAC cohorts (177 days); however, apixaban patients had 0.5 more days at home compared to rivaroxaban patients. Across all NOAC cohorts, 7–8% had a claim for a S/SE, 11–15% had a claim for bleeding, and 15–22% had an INR test, while 87–89% of all patients had an AF-claim during the 180-day follow-up. Patients prescribed apixaban had 1 more day at home without external AF-related care compared to dabigatran, and 1.5 more days at home without external AF-related care compared to rivaroxaban. Dabigatran had &amp;lt;1 more day at home without external AF-related care compared to rivaroxaban. Conclusion Among NVAF patients treated with NOACs, there were small differences in the time at home and time at home without external AF-related care during the first 6 months of NOAC treatment. As NVAF is a chronic condition, it is important to understand the impact of NOAC treatment on these patient-centered outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol-Myers Squibb Company and Pfizer Inc.

Rivaroxaban versus Warfarin in the Management of Deep Venous Thrombosis

Abstract Background Deep venous thrombosis (DVT) refers to the formation of one or more blood clots in one of the body’s large veins, most commonly in the lower limbs. The clot can cause partial or complete blocking of circulation in the vein, which in some patients leads to pain, swelling, tenderness, discolouration of the skin that is warm to touch. Aim of the Work Compare the effect of direct Oral Anticoagulant (Rivaroxaban) versus Antivitamin K (warfarin) in treatment of lower limb Deep Venous Thrombosis. Patients and Methods Type of study: prospective single blinded randomized study, study setting: was conducted at Kobri Elkobba hospitals, study period: 6 months, study population: Eligible all patients above 18 years had femoropopliteal vein thrombosis, confirmed with duplex ultrasound scanning and D-dimer test and qualified under the inclusion and exclusion criteria of the study. Results Our study shows that Rivaroxaban alone is as effective as standard therapy, with similar safety, for the treatment of acute DVT and in preventing recurrence and has low risk of bleeding. There was statistically significant increase in INR monitoring during 6 months in warfarin group than Rivaroxaban group with p-value &amp;lt; 0.001. This because warfarin has many drug and food interaction. There's no response in treatment out come after 3 months duplex as the study was on patient of femoro popliteal DVT, however there were clinical improvement in both groups. Complete recanalization with normal augmentation by muscle compression occurred in all Rivaroxaban patients compared to 5% were partially compressible with incomplete recanalization in warfarin group after 6 months of treatment. Conclusion We concluded in patients with unprovoked VTE, rivaroxaban has the potential to reduce both the risk of major bleeding and recurrent VTE compared to warfarin. And there’s no need for adjusting the dose and INR monitoring, and Rivaroxaban has no food nor drug interactions.

Kidney, limb and ophthalmic complications, and death in patients with nonvalvular atrial fibrillation and type 2 diabetes prescribed rivaroxaban or warfarin: an electronic health record analysis

Background Patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes are at risk of kidney, limb, and ophthalmic complications. We evaluated the rate of these complications and death in patients with NVAF and type 2 diabetes prescribed rivaroxaban or warfarin. Methods We analyzed Optum de-Identified electronic health record (EHR) data from 11/2010–12/2019. We included adults with NVAF and T2D newly initiated on rivaroxaban or warfarin with ≥12 months of prior EHR activity. Patients with another indication for anticoagulation, valve disease, history of end-stage renal disease, major adverse limb events (MALE), diabetic retinopathy or pregnancy were excluded. We evaluated the incidence rate of developing a composite outcome of >40% decrease in estimated glomerular filtration incidence rate (eGFR) from baseline, eGFR < 15 mL/minute/1.73 m2, need for dialysis or kidney transplant, MALE, diabetic retinopathy or death. Overlap weighting was used to balance baseline characteristics between cohorts while preserving sample size. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted Cox regression. Results We included 24,912 rivaroxaban and 58,270 warfarin users. The mean ± standard deviation (SD) CHA2DS2VASc score was 4.3 ± 1.5 and modified HASBLED score was 1.5 ± 0.8. Thirty percent of rivaroxaban patients were started on 15 mg once daily, with the rest prescribed 20 mg once daily. Warfarin patients had a mean time in therapeutic range of 47 ± 28%. Patients were followed for a mean of 2.89 ± 1.95 years. Rivaroxaban was associated with a reduced hazard of the composite outcome (HR = 0.93, 95%CI = 0.91–0.95; absolute risk reduction = 1.97 events per 1000 patient-years; number needed-to-treat = 51) versus warfarin. Rivaroxaban was also associated with significant reductions in the relative hazard of > 40% decrease in eGFR from baseline (HR = 0.96), need for dialysis or renal transplant (HR = 0.81), and limb revascularization or major amputation (HR = 0.85). Death occurred at a lower incidence rate with rivaroxaban (HR = 0.92, 95%CI = 0.89–0.95). Conclusions Rivaroxaban was associated with reduced incidence rates of kidney and limb complications, and death in NVAF patients with type 2 diabetes compared to warfarin. ClinicalTrials.gov Identifier: NCT04509193

Risk of Stroke Outcomes in Atrial Fibrillation Patients Treated with Rivaroxaban and Warfarin

ObjectivesIn a previous real-world study, rivaroxaban reduced the risk of stroke overall and severe stroke compared with warfarin in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to assess the reproducibility in a different database of our previously observed results (Alberts M, et al. Stroke. 2020;51:549-555) on the risk of severe stroke among NVAF patients in a different population treated with rivaroxaban or warfarin. Material and MethodsThis retrospective cohort study included patients from the IBM® MarketScan® Commercial and Medicare databases (2011-2019) who initiated rivaroxaban or warfarin after a diagnosis of NVAF, had ≥6 months of continuous health plan enrollment, had a CHA2DS2-VASc score ≥2, and had no history of stroke or anticoagulant use. Patient data were assessed until the earliest occurrence of a primary inpatient diagnosis of stroke, death, end of health plan enrollment, or end of study. Stroke severity was defined by National Institutes of Health Stroke Scale (NIHSS) score, imputed by random forest model. Cox proportional hazard regression was used to compare risk of stroke between cohorts, balanced by inverse probability of treatment weighting. ResultsThe mean observation period from index date to either stroke, or end of eligibility or end of data was 28 months. Data from 13,599 rivaroxaban and 39,861 warfarin patients were included. Stroke occurred in 272 rivaroxaban-treated patients (0.97/100 person-years [PY]) and 1,303 warfarin-treated patients (1.32/100 PY). Rivaroxaban patients had lower risk for stroke overall (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.76–0.88) and for minor (NIHSS 1 to <5; HR, 0.83; 95% CI, 0.74–0.93), moderate (NIHSS 5 to <16; HR, 0.88; 95% CI, 0.78–0.99), and severe stroke (NIHSS 16 to 42; HR, 0.44; 95% CI, 0.22–0.91). ConclusionsThe results of this study in a larger population of NVAF patients align with previous real-world findings and the ROCKET-AF trial by showing improved stroke prevention with rivaroxaban versus warfarin across all stroke severities.

Clinical and Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients With Coronary Artery Disease and/or Peripheral Artery Disease

To address literature gaps on treatment with real-world evidence, this study compared effectiveness, safety, and cost outcomes in NVAF patients with coronary or peripheral artery disease (CAD, PAD) prescribed apixaban versus other oral anticoagulants. NVAF patients aged ≥65 years co-diagnosed with CAD/PAD initiating warfarin, apixaban, dabigatran, or rivaroxaban were selected from the US Medicare population (January 1, 2013 to September 30, 2015). Propensity score matching was used to match apixaban versus warfarin, dabigatran, and rivaroxaban cohorts. Cox models were used to evaluate the risk of stroke/systemic embolism (SE), major bleeding (MB), all-cause mortality, and a composite of stroke/myocardial infarction/all-cause mortality. Generalized linear and two-part models were used to compare stroke/SE, MB, and all-cause costs between cohorts. A total of 33,269 warfarin-apixaban, 9,335 dabigatran-apixaban, and 33,633 rivaroxaban-apixaban pairs were identified after matching. Compared with apixaban, stroke/SE risk was higher in warfarin (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.61 to 2.31), dabigatran (HR: 1.69; 95% CI: 1.18 to 2.43), and rivaroxaban (HR: 1.24; 95% CI: 1.01 to 1.51) patients. MB risk was higher in warfarin (HR: 1.67; 95% CI: 1.52 to 1.83), dabigatran (HR: 1.37; 95% CI: 1.13 to 1.68), and rivaroxaban (HR: 1.87; 95% CI: 1.71 to 2.05) patients vs apixaban. Stroke/SE- and MB-related medical costs per-patient per-month were higher in warfarin, dabigatran, and rivaroxaban patients versus apixaban. Total all-cause health care costs were higher in warfarin and rivaroxaban patients compared with apixaban patients. In conclusion, compared with apixaban, patients on dabigatran, rivaroxaban, or warfarin had a higher risk of stroke/SE, MB, and event-related costs.

Healthcare costs before and after stroke in patients with non-valvular atrial fibrillation who initiated treatment with rivaroxaban or warfarin

Aims Rivaroxaban reduces stroke compared with warfarin in patients with non-valvular atrial fibrillation (NVAF). This study compared healthcare costs before and after stroke in NVAF patients treated with rivaroxaban or warfarin. Materials and methods Using de-identified IBM MarketScan Commercial and Medicare databases, this retrospective cohort study (from 2011 to 2019) included patients with NVAF who initiated rivaroxaban or warfarin within 30 days after initial NVAF diagnosis. Patients who developed stroke were identified, and stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) score, imputed by a random forest method. Total all-cause per-patient per-year (PPPY) costs of care were determined for patients: (1) who developed stroke during the pre- and post-stroke periods and (2) who remained stroke-free during the follow-up period. Treatment groups were balanced using inverse probability of treatment weighting. Results A total of 13,599 patients initiated rivaroxaban and 39,861 initiated warfarin, of which 272 (2.0%) and 1,303 (3.3%), respectively, developed stroke during a mean follow-up of 28 months. Among patients who developed stroke, PPPY costs increased from the pre-stroke to post-stroke period, with greater increases in the warfarin cohort relative to the rivaroxaban cohort. Overall, the costs increased by 1.78-fold for rivaroxaban vs 3.07-fold for warfarin; for less severe strokes (NIHSS < 5), costs increased 0.88-fold and 1.05-fold, respectively. Cost increases for more severe strokes (NIHSS ≥ 5) among rivaroxaban patients were half those for warfarin patients (3.19-fold vs 6.37-fold, respectively). Among patients without stroke, costs were similar during the follow-up period between the two treatment groups. Conclusions Total all-cause costs of care increased in the post-stroke period, and particularly in the patients treated with warfarin relative to those treated with rivaroxaban. The lower rate of stroke in the rivaroxaban cohort suggests that greater pre- to post-stroke cost increases result from more strokes occurring in the warfarin cohort.