Rivaroxaban In Patients Research Articles

Retrospective evaluation of the efficacy and safety of rivaroxaban in patients with cancer-associated venous thromboembolism: A single-center study.

AbstrctThe purpose of this study was to evaluate the efficacy and safety of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE).We performed a retrospective chart review of cancer patients with a pulmonary embolism, deep vein thrombosis, or both. Our analysis included all patients who received rivaroxaban from March 2013 to June 2016 at the Hemato-Oncology Division at the Pusan National University Hospital in Korea.Preliminary results identified 123 patients with a history of cancer that were treated with rivaroxaban. The average duration of rivaroxaban therapy was 95.25 days. While 35 patients had resolved VTE after the initiation of rivaroxaban, only one patient had it recur on rivaroxaban treatment. Major bleeding was observed in 6 (4.9%) patients and minor bleeding in 12 (9.8%) patients. The majority of bleeding events occurred spontaneously and most incidences of bleeding could be treated conservatively. Recurrence and major bleeding events on rivaroxaban were relatively low despite the fact that many patients had metastatic disease. Among 52 patient deaths (42.3%), none were due to VTE or bleeding complications; the cause of death in the majority of cases was cancer progression.Rivaroxaban is effective and safe for the treatment of cancer-associated VTE.

Comparative effectiveness of rivaroxaban versus a vitamin K antagonist in patients with renal impairment treated for non-valvular atrial fibrillation in Germany — A retrospective cohort study

BackgroundThe risk of thromboembolic events is increased in patients with non-valvular atrial fibrillation (NVAF) and renal impairment. The risk of bleeding events is increased if these patients are treated with anticoagulants and further increased in those with active cancer. MethodsRELOAD, a retrospective database study, assessed the outcomes of patients with NVAF prescribed rivaroxaban versus phenprocoumon. Here, we present a subgroup analysis evaluating effectiveness and safety of rivaroxaban versus phenprocoumon in patients with NVAF and renal impairment. Analyses were additionally stratified by patients with and without evidence of cancer at baseline. ResultsWhen using the ‘one tablet per day’ definition of estimating drug exposure time, the incidence of the primary endpoint of ischaemic stroke was significantly lower in patients (without evidence of cancer at baseline) receiving rivaroxaban 15 mg or 20 mg once daily versus those receiving phenprocoumon (2.40 vs 3.51 events per 100 patient-years, respectively; hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.55–0.94, p = 0.015); with the incidence of the primary safety outcome of intracranial haemorrhage being numerically lower (0.57 vs 0.89 events per 100 patient-years, respectively; HR = 0.66, 95% CI 0.38–1.14, p = 0.14). Similar results were observed when using the ‘empirical defined daily dose’ definition to estimate drug exposure time and when including patients with evidence of cancer. ConclusionThe prescription of rivaroxaban in patients with NVAF and renal impairment was associated with a lower incidence of ischaemic stroke and intracranial haemorrhage versus phenprocoumon in patients without evidence of cancer.

Real-world 2-year outcome of atrial fibrillation treatment with dabigatran, apixaban, and rivaroxaban in patients with and without chronic kidney disease.

Patients with non-valvular atrial fibrillation (NVAF) and chronic kidney disease (CKD) are at increased risk of stroke and bleeding. Although direct oral anticoagulant (DOAC) trials excluded patients with severe CKD, a growing portion of CKD patients have been starting DOACs and limited data from real-world outcome in this high-risk setting are available. The INSigHT registry included 632 consecutive NVAF patients that started apixaban (256 patients, 41%), dabigatran (245, 39%) and rivaroxaban (131, 20%) between 2012 and 2015. Based on creatinine clearance, two sub-cohorts were defined: (1) non-CKD group (CrCl 60-89mL/min, 413 patients) and (2) CKD group (15-59ml/min, 219). Compared to non-CKD patients, those with CKD, were at higher ischemic (CHA2DS2-VASc 4.5 vs 2.9, p < 0.001) and hemorrhagic risk (HAS-BLED 2.4 vs 1.8, p < 0.001). At 2-year follow-up, the overall ISTH-major bleeding and thromboembolic event rates were 5.2% and 2.3% and no significant difference between non-CKD and CKD patients for both efficacy and safety endpoints were observed. In non-CKD patients, the 2-year ISTH-major bleeding rates were higher in rivaroxaban group (HR 2.9, 95% CI 1.1-7.3; p = 0.047) while dabigatran showed non-significant excess in thromboembolic events (HR 4.3, 95% CI 0.9-20.8; p = 0.068). In CKD patients, a significantly higher rate of thromboembolic events was observed in rivaroxaban (HR 6.3, 95% CI 1.1-38.1; p = 0.044). This real-world, non-insurance database registry shows remarkable 2-year safety and efficacy profile of DOACs even in patients with moderate to severe CKD. Head to head differences between DOACs are exploratory, hypothesis generating and warrant further investigation in larger studies.

Rivaroxaban in atrial fibrillation cardioversion: an update.

Currently, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population, representing a powerful risk factor for stroke and systemic thromboembolism and increased mortality and morbidity. Restoration of sinus rhythm is an important treatment option in AF and has a high success rate, but there is the need for an effective anticoagulation strategy to reduce the risk of embolic events. Anticoagulation with vitamin K antagonists is often associated with failure to achieving effective international normalized ratio. In this setting, recent data have led to extended approval for rivaroxaban in clinical practice, because it is effective and safe in patients with AF undergoing cardioversion, avoiding additional health costs and related time loss, while improving patient satisfaction. The present report provides an overview of the main randomized controlled trial and the main real-life studies, documenting the use of rivaroxaban in patients with non-valvular AF who underwent the cardioversion procedure. Considering that novel non-vitamin K antagonist oral anticoagulants in left atrial appendage thrombi resolution is still unknown in the real-world practice, the main findings on the use of rivaroxaban in this setting are also discussed.

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism

ObjectiveTo compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE). Patients and MethodsConsecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB. ResultsWithin the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer. ConclusionIn the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.

Abstract WP524: Outcomes With Rivaroxaban in Patients With Nonvalvular Atrial Fibrillation and Worsening Renal Function

Introduction: Direct oral anticoagulants are widely used in patients with nonvalvular atrial fibrillation (AF) to reduce the risk of stroke and systemic embolism, however, there is not enough real-world data of their effectiveness and safety in patients with worsening renal function (WRF). Xarelto post-authorization safety and effectiveness study in Japanese patients with atrial fibrillation (XAPASS) is a prospective observational post-marketing surveillance study mandated by the Japanese authority. It aims to examine safety and effectiveness of rivaroxaban in everyday clinical practice. This analysis investigated one year outcomes among patients with WRF and stable renal function (SRF) in XAPASS. Methods: One year follow-up data of 9578 patients enrolled in XAPASS were analyzed to evaluate baseline characteristics and safety/effectiveness profile among patients with WRF and SRF. WRF was defined as a decrease of more than 20% from enrollment creatinine clearance measurement at any time point during the study. SRF was defined as the absence of WRF at any time. Results: We identified 1229 patients (12.8%) with WRF and 6280 patients (65.6%) with SRF among 9578 patients. WRF patients were significantly older, and had significantly higher mean CHA 2 DS 2 -VASc score and modified HAS-BLED score compared to SRF patients. Prevalence of hypertension, congestive heart failure, ischemic stroke/transient ischemic attack, and myocardial infarction was higher in WRF patients. There was no difference in rates of major bleeding (hazard ratio (HR) 1.20; 95% confidence interval (CI) 0.75-1.90; p=0.45) or the composite endpoint of stroke, systemic embolism or myocardial infarction (HR 1.06; 95% CI 0.65-1.71; p=0.82) between patients with WRF and SRF. WRF patients experienced a higher incidence of transfusion of 2 units or more (0.46 versus 0.14 events per 100 patient-years; HR 3.19; 95% CI 1.04-9.74; p=0.03) versus SRF patients. Rates of other major bleeding subgroups defined according to ISTH criteria were similar between patients with WRF and SRF. Conclusions: WRF during rivaroxaban treatment did not significantly increase the rates of major bleeding or thromboembolic events, although it was associated with a higher incidence of transfusion of 2 units or more.

ATRIAL FIBRILLATION COMBINED WITH DIABETES MELLITUS. POSSIBILITIES OF USING RIVAROXABAN

The presented material summarizes the main clinical and theoretical data on the peculiarities of atrial fibrillation (AP) flow in combination with diabetes mellitus (DM). This combination, although associated with a lower age than in patients without diabetes, is associated with a higher risk of stroke and systemic embolism and other adverse complications. The material presents the data of the rocket-AF randomized trial subanalysis on the peculiarities of the use of oral anticoagulant - a direct inhibitor of Xa-factor Rivaroxaban in patients with non-valve AF in combination with DM. Comparative efficacy and safety of Rivaroxaban in patients with diabetes were comparable to those in patients without diabetes. Rivaroxaban in patients with diabetes was associated with lower vascular death rates than warfarin. The results of the randomized trial are largely confirmed in several observational studies that reflect actual clinical practice. Thus, it can be affirmed that Rivaroxaban is not only the most commonly used direct oral anticoagulant in russian practice, but can also be widely used in patients with non-valve AF and diabetes to prevent strokes and systemic embolisms.

Factors Associated with Bleeding Events in Patients Receiving Rivaroxaban for Venous Thromboembolism: A Real World Experience

Introduction:Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE.Methods:A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (>2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained.Results:The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events.Conclusion:In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. DisclosuresNo relevant conflicts of interest to declare.

Treatment of deep vein thrombosis with rivaroxaban and its potential to prevent the post-thrombotic syndrome.

The study was initiated following the observation of complete recanalization of thrombus in subjects with DVT treated with rivaroxaban after 1-2 weeks. The aim of this observational retrospective study was to evaluate clinically and by means of echo color Duplex, the fibrinolytic effect of rivaroxaban in patients with recent and previous DVT. To accomplish this two populations of patients were evaluated. Group 1 was comprised of 31 patients (ranging in age 52-73 years) with popliteal-femoral DVT (12 months ago) treated with standard anticoagulant therapy. In these patients, we found a complete superficial femoral recanalization and partial recanalization of the popliteal vein (30% of residual thrombus). The patients had normal creatinine clearance and liver function. The patients were switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy. Group 2 was comprised of 22 patients (ranging in age 65-82 years) with previous popliteal-femoral DVT and documented complete common femoral veins recanalization who presented with a recent superficial femoral vein re-thrombosis (1 week before). The patients had normal creatinine clearance and liver function. The patients switched from warfarin to rivaroxaban due to a lack of compliance with warfarin therapy. In group 1, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks of rivaroxaban therapy. In group 2, all patients exhibited the complete recanalization of the popliteal veins after 4 weeks, and the complete recanalization of the acute re-thrombosis of the superficial femoral veins after 2 weeks of rivaroxaban therapy. No adverse events for both groups were observed. Our results suggest that rivaroxaban could have a pro-fibrinolytic effect not only on recent thrombus but also on organized thrombus that results in a complete recanalization of affected veins. It is proposed that this lytic effect will preserve venous valve structure and lead to a reduction of incidence of post-thrombotic syndrome in rivaroxaban treated patients.

Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease

BackgroundHeart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease.MethodsIn this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. The principal safety outcome was fatal bleeding or bleeding into a critical space with a potential for causing permanent disability.ResultsOver a median follow-up period of 21.1 months, the primary end point occurred in 626 (25.0%) of 2507 patients assigned to rivaroxaban and in 658 (26.2%) of 2515 patients assigned to placebo (hazard ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P=0.27). No significant difference in all-cause mortality was noted between the rivaroxaban group and the placebo group (21.8% and 22.1%, respectively; hazard ratio, 0.98; 95% CI, 0.87 to 1.10). The principal safety outcome occurred in 18 patients who took rivaroxaban and in 23 who took placebo (hazard ratio, 0.80; 95% CI, 0.43 to 1.49; P=0.48).ConclusionsRivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation. (Funded by Janssen Research and Development; COMMANDER HF ClinicalTrials.gov number, NCT01877915.)

Efficacy and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and a history of cancer: observations from ROCKET AF.

The management of anticoagulation therapy in patients with atrial fibrillation (AF) and cancer is challenging due to increased thrombotic and bleeding risks. We sought to determine the safety and efficacy of rivaroxaban in patients with AF and a history of cancer. ROCKET AF randomized 14264 patients with AF to rivaroxaban or warfarin with a median follow-up of 1.9 years. Cox regression models were used to assess the association between cancer history and clinical outcomes, and the relative treatment effect of rivaroxaban vs. warfarin in these patients. A total of 640 patients enrolled in ROCKET AF had a history of cancer, with the most common types being prostate (28.6%), colorectal (16.1%), and breast (14.7%) cancer. Patients with a history of cancer were older, more frequently male, more likely to have prior vitamin K antagonist (VKA) use and had higher rates of overall bleeding [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.16-1.47; P < 0.0001] and non-cardiovascular death (HR 1.47, 95% CI 1.04-2.07; P = 0.031) compared with those with no cancer history. There were no significant associations between cancer history and stroke, venous thromboembolism, or myocardial infarction. The relative efficacy of rivaroxaban vs. warfarin for prevention of stroke/systemic embolism was similar in those with and without a history of cancer (interaction P-value = 0.21). In ROCKET AF, a history of cancer was associated with a higher risk of bleeding and non-cardiovascular death, but not ischaemic events. The relative efficacy and safety of rivaroxaban compared with warfarin were not significantly different in patients with and without a history of cancer. The results of this study are exploratory and should be taken in context of the study population, which may not be generalizable to those with advanced malignancy. Further investigation is needed to understand optimal anticoagulation strategies in patients with AF and cancer.Clinical trial registration: ClinicalTrials.gov: NCT00403767.

Rivaroxaban in Patients with Heart Failure and Reduced Ejection Fraction, but Without Afib

Chronic anticoagulation in patients with heart failure and reduced ejection fraction (HFrEF), but without atrial fibrillation (Afib, AF), has long been

The prothrombin time does not predict the risk of recurrent venous thromboembolism or major bleeding in rivaroxaban-treated patients

IntroductionFor treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), rivaroxaban is given in fixed doses without routine coagulation monitoring. Patients and methodsTo determine whether monitoring would enhance its benefit-risk profile, we examined whether peak and trough prothrombin time (PT) values measured in 3797 rivaroxaban-treated patients included in the EINSTEIN DVT and PE studies correlated with subsequent recurrent VTE and major bleeding. In addition, we examined the stability of PT values over time and the impact of clinical variables on PT values. ResultsThe mean peak PT values at months 3 and 6 or 12 were 21.9 ± 5 and 21.7 ± 6.0 s, respectively, while the mean trough PT values at months 2 and 6 were 15.1 ± 5.1 and 15.3 ± 2.9 s, respectively. Although peak and through PT values were higher in females, and with older age, frailty, active cancer, low body weight, impaired renal function and use of moderate to strong inhibitors of CYP3A4 and/or P-glycoprotein, and were lower in patients taking strong CYP 3A4 inducers, the differences were small and results were overlapping. Neither peak nor trough PT values correlated with recurrent VTE or major bleeding. ConclusionsPT monitoring is unlikely to improve the benefit-risk profile of rivaroxaban in patients with DVT or PE.The study was registered at www.clinicaltrials.gov as #NCT00440193 (EINSTEIN-DVT) and #NCT00439777 (EINSTEIN-PE).

Usefulness and Safety of Rivaroxaban in Patients Following Isolated Mitral Valve Replacement With a Mechanical Prosthesis

Rivaroxaban has previously been tested in experimental and animal models with encouraging results. We prospectively selected seven patients between May 2017 and January 2018 who underwent isolated mitral valve replacement with a mechanical prosthesis and had unstable INR control at least 3 months after surgery. An intervention of rivaroxaban 15mg was then administered twice daily for a period of 90days. No patient presented intracardiac thrombus, reversible ischemic neurological deficit, ischemic or hemorrhagic stroke, and hospitalization or death during 3 months of follow-up. Two patients eradicated the presence of spontaneous echo contrast. Mean and peak pressure gradients, peak velocity, effective orifice area, and PHT were similar before and after the intervention. In conclusion, the use of rivaroxaban for 90days in seven patients after replacement of mitral valve with the mechanical prosthesis did not present thromboembolic or bleeding events (NCT02894307).

Direct oral anticoagulants for stroke prevention in atrial fibrillation: treatment outcomes and dosing in special populations

To review data from the pivotal phase III trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), and to summarize the major findings with regards to patient subgroups that are at an increased risk for stroke or bleeding. A PubMed literature search (January 2009 to January 2017) was performed using the terms 'dabigatran', 'rivaroxaban', 'apixaban', 'edoxaban', 'atrial fibrillation', 'RE-LY', 'ROCKET AF', 'ARISTOTLE', and 'ENGAGE AF-TIMI 48'. All primary publications and secondary analyses in special populations at increased risk of stroke or bleeding from the pivotal phase III clinical trials were evaluated. Available secondary analyses indicate no treatment interactions with regards to stroke or systemic embolic event (SEE) prevention for any of the DOACs in the patient subgroups, including patients with advanced age, impaired renal function, diabetes, prior stroke, concomitant antiplatelet therapy, heart failure, prior stroke, history of hypertension, myocardial infarction (MI), coronary artery disease, and peripheral artery disease (PAD). Although higher bleeding incidence was reported with dabigatran and rivaroxaban in patients aged 75 years and over with apixaban in patients with diabetes, and with rivaroxaban in patients with previous MI or PAD, no changes in dosing are recommended. Overall, results of secondary analyses indicate that the recommended dosing strategy for each of the DOACs produces a consistent anticoagulant effect across a diverse patient population, including those at increased risk of stroke or bleeding.

Combined use of topical intraarticular tranexamic acid and rivaroxaban in total knee arthroplasty safely reduces blood loss, transfusion rates, and wound complications without increasing the risk of thrombosis

BackgroundBlood loss and deep vein thrombosis (DVT) are important complications after total knee arthroplasty (TKA). Topical tranexamic acid (TXA) effectively reduces wound bleeding but may elevate the risk of DVT. In contrast, rivaroxaban potently prevents DVT but has been associated with bleeding complications. The simultaneous use of topical TXA and rivaroxaban in TKA has not been much investigated.MethodsA retrospective cohort study was conducted with two consecutive groups of patients who underwent TKA. Intraoperatively, one group (RVTX group) received topical, intraarticular TXA, while the other (RV group) did not. Both groups were administered rivaroxaban postoperatively for 14 days and underwent Doppler ultrasound for DVT screening. After propensity score matching, both groups consisted of 52 patients (104 patients in total) and were compared regarding total drain output, nadir haemoglobin (Hb), maximum Hb decrease, calculated total blood loss, transfusion rate, and incidence of DVT and wound complications.ResultsBoth groups showed no significant differences in the propensity-matched variables of age, sex, body mass index, American Society of Anesthesiologists physical status score, and preoperative Hb. The RVTX group showed a significantly higher nadir Hb (p < 0.001), lower drain output (p < 0.001), Hb decrease (p = 0.015), total blood loss (p < 0.001), and rate of transfusion (p < 0.001) and fewer wound complications (p = 0.027). However, the incidence of DVT (p = 1.000) did not differ significantly between the two groups, and all cases were asymptomatic.ConclusionsThe combined use of intraarticular topical TXA with rivaroxaban in patients undergoing TKA is a safe and effective method to reduce blood loss, the need for transfusion, and wound complications without elevating the risk of DVT.

Primary and secondary prevention of stroke and systemic embolism with rivaroxaban in patients with non-valvular atrial fibrillation

The EXPAND Study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). In this sub-analysis, we compared the differences in efficacy and safety between patients with and those without history of stroke or transient ischemic attack (TIA). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients aged ≥ 20 years [mean age 71.6 ± 9.4 (SD) years] who were being or planned to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for a mean period of 897.1 ± 206.8 days with a high follow-up rate (99.7%). The primary prevention group comprised patients without history of ischemic stroke or TIA (n = 5546, 77.7%), and the secondary prevention group comprised those with history of ischemic stroke or TIA (n = 1595, 22.3%). In the primary and secondary prevention groups, the incidence rate of stroke or SE (primary efficacy endpoint) was 0.7 and 2.2%/year, respectively (P < 0.001), and the incidence rate of major bleeding (primary safety endpoint) was 1.2 and 1.5%/year, respectively (P = 0.132). For major bleeding events, the incidence rate of intracranial bleeding was 0.4 and 0.8%/year (P = 0.002) in the primary and secondary prevention groups, respectively. This sub-analysis of the EXPAND Study showed that the Japan-specific dosages of rivaroxaban were effective and safe in Japanese NVAF patients with and those without ischemic stroke or TIA in routine clinical practice.

Pilot trials in thrombosis: Purpose and pitfalls

Randomized controlled trials provide important evidence to guide clinical practice. These full‐scale trials are expensive, time consuming and many are never successfully completed. Well conducted pilot studies help with full‐scale trial design, assessment and optimization of feasibility, and can avoid the waste of resources associated with starting a full‐scale trial that will not succeed. They also provide an opportunity for capacity growth and mentorship of new investigators. It is important to appreciate that the usual goal of a pilot trial is assessment of feasibility and refinement of trial design rather than to gain preliminary evidence of efficacy. Indeed, using event rates from a pilot trial to calculate sample sizes can be misleading in therapeutic trials. Misconceptions exist that pilot trials are just “small trials,” are easy to perform, and are not worthy of publication. While, in the past, many pilot trials were poorly conducted and not followed by a full‐scale trial, by following the recommendations in the “CONSORT 2010 statement: extension to randomized pilot and feasibility trials,” high‐quality pilot trials can be performed and reported that will greatly improve the chances of successfully completing a practice‐changing trial. We propose that pilot trials are a valuable investment and describe the TRIM‐Line pilot trial (NCT03506815), a pilot study assessing the feasibility of a randomized controlled trial investigating primary thromboprophylaxis with rivaroxaban in patients with malignancy and central venous catheters, as an illustrative example of how a pilot trial in the area of thrombosis should be designed.

STUDY OF RIVAROXABAN FOR VENOUS THROMBOEMBOLISM PROPHYLAXIS AFTER LOWER EXTREMITY FRACTURES IN RUSSIAN CLINICAL PRACTICE

Thepurposeof the study was to evaluate the efficacy and safety of rivaroxaban in patients after surgical treatment for the lower extremity fractures.Patients and methods. Retrospective multicenter study included 663 patients with femur fractures, 43 patients with complications after total hip arthroplasty (periprosthetic femur fractures, recurrent dislocation) and 10 patients with shinbone fractures. The majority (81.99%) of patients were elderly or senile. In postoperative period all patients received a standard prophylactic dose of anticoagulants. Out of them 75 (main group) – rivaroxaban (10 mg/day), 241 (control group) – other drugs (enoxaparin – 40 mg/day and dabigatran etexilate 150 or 220 mg/day). The efficacy of prophylaxis was assessed by clinical picture and Doppler ultrasound scans.Results.Average bed day made up 9.28. During hospitalization no cases of PE were recorded. In the main and control groups the rate of deep vein thrombosis with clinical manifestations made up 1.89 and 3.31%, respectively. No cases of fatal bleeding occurred. Signs of continuous bleeding in the area of surgical intervention (soaking dressings or recurring wound hematomas) in the main group was recorded rarely (3.15%) than in the control one (8.29%).Conclusion.Reduction of VTE rate with no increase in bleeding risk indicates the feasibility of rivaroxaban use for postoperative PE prophylaxis in patients with lower extremity fractures.

Comparative effectiveness and safety of apixaban, dabigatran, and rivaroxaban in patients with non-valvular atrial fibrillation

BackgroundThe comparative effectiveness and safety of individual direct oral anticoagulants (DOACs) in clinical practice is largely unknown. The study objectives were to compare effectiveness and safety of DOACs in patients with non-valvular atrial fibrillation (NVAF). MethodsBased on nationwide registers we established a population-based historical cohort study of 12,638 new users of standard dose DOACs (apixaban 5 mg twice daily, dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily) with NVAF in Denmark, July 2013 to March 2016. Patients were matched on propensity scores in a 1:1 ratio comparing apixaban vs. dabigatran (for a total of 6470 patients), apixaban vs. rivaroxaban (7352 patients), and rivaroxaban vs. dabigatran (5440 patients). Hazard ratios (HRs) for stroke or systemic embolism (effectiveness outcome) and major bleeding (safety outcome) were estimated. ResultsIn propensity-matched comparisons of the risk of stroke or systemic embolism, the HRs were 1.27 (95% confidence interval [CI], 0.82–1.96) for apixaban vs. dabigatran, 1.25 (95% CI, 0.87–1.79) for apixaban vs. rivaroxaban, and 1.17 (95% CI, 0.69–1.96) for rivaroxaban vs. dabigatran. For the risk of major bleeding, the HRs were 0.94 (95% CI, 0.62–1.41) for apixaban vs. dabigatran, 0.88 (95% CI, 0.64–1.22) for apixaban vs. rivaroxaban, and 1.35 (95% CI, 0.91–2.00) for rivaroxaban vs. dabigatran. ConclusionsAmong patients with NVAF in routine clinical practice, there were no statistically significant differences in risk of stroke or systemic embolism or major bleeding in propensity-matched comparisons between apixaban, dabigatran, and rivaroxaban used in standard doses. While analyses indicate that more than moderate differences can be excluded, smaller differences cannot be ruled out.