Rivaroxaban,an oral direct factor Xa inhibitor

Rivaroxaban is a small molecule, direct Factor Xa inhibitor and may be a potentially attractive alternative to vitamin K antagonists. Rivaroxaban is being investigated for the prevention and treatment of venous and arterial thrombosis. A broad search of Medline, clinicaltrials.gov and the annual proceedings of the American Society of Hematology and the International Society on Thrombosis and Hemostasis was conducted. This review addresses the findings of this systematic search, including the need for new oral anticoagulants, the development and pharmacology of rivaroxaban, and the results of completed as well as ongoing trials with rivaroxaban. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in Phase II and Phase III trials involving over 24,000 patients. Additionally, rivaroxaban is being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The drug may have its greatest impact in providing a much-needed and attractive alternative to warfarin. Further data (especially large Phase III trials) are required.     

Comparison of the efficacy of rivaroxaban and dabigatran etexilate in preventing venous thrombosis after arthroplasty: A protocol of randomized controlled trial

Background:New oral anticoagulants (NOAC) are gradually accepted by clinical practice for its convenient route of administration and stable effect. Both rivaroxaban and dabigatran etexilate have been used in the prevention and treatment of venous embolism after arthroplasty, but there is a lack of direct comparison between the 2 effects. Therefore, the purpose of this randomized controlled trial was to evaluate the efficacy and safety of 2 new oral anticoagulants, rivaroxaban, and dabigatran etexilate, in the prevention of venous thromboembolism after joint replacement.Methods:This is a prospective randomized controlled trial to study the efficacy and safety of rivaroxaban and dabigatran etexilate in the prevention of venous thromboembolism after joint replacement, and is approved by the clinical research ethics of our hospital. Patients were randomly divided into 1 of 2 treatment regimens:

• (A)rivaroxaban oral group and
• (B)dabigatran etexilate oral group.

Patients, doctors, nurses, and data collection assistants were blinded to group allocation. The indicators of observation include:

• (1)validity indicators: asymptomatic deep venous thrombosis (DVT), symptomatic DVT, symptomatic pulmonary embolism (PE) incidence, all-cause mortality;
• (2)safety indicators: incidence of major bleeding and clinically related non-major bleeding events and other adverse events.

Data were analyzed using the statistical software package SPSS version 25.0 (Chicago, IL).Discussion:This study will evaluate the efficacy and safety of rivaroxaban and dabigatran etexilate in preventing venous thrombosis after joint replacement. The results of this experiment will provide clinical basis for the use of rivaroxaban or dabigatran etexilate to prevent venous thrombosis after joint replacement.Ethics and dissemination:Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/QVDCW.     

Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients

BackgroundHospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown.ObjectivesThe purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge.MethodsMARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events.ResultsIn total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398).ConclusionsExtended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564)     

Use of risk scores to identify lower and higher risk subsets among COMPASS‐eligible patients with chronic coronary syndromes. Insights from the CLARIFY registry

BackgroundThe COMPASS trial showed a reduction of ischemic events with low‐dose rivaroxaban and aspirin in chronic coronary syndromes (CCS) compared with aspirin alone, at the expense of increased bleeding.HypothesisThe CHA₂DS₂VaSc Score, REACH Recurrent Ischemic (RIS), and REACH Bleeding Risk Score (BRS) could identify patients with a favorable trade‐off between ischemic and bleeding events, among COMPASS‐eligible patients.MethodsWe identified the COMPASS‐eligible population within the CLARIFY registry (>30.000 patients with CCS). High‐bleeding risk patients (REACH BRS > 10) were excluded, as in the COMPASS trial. Patients were categorized as low (0–1) or high (≥ 2) CHA₂DS₂VaSc; low (0–12) or intermediate (13–19) REACH RIS, and low (0–6) or intermediate (7–10) REACH BRS. Ischemic outcome was the composite of cardiovascular death, myocardial infarction or stroke. Bleeding was defined as serious bleeding (haemorrhagic stroke, hospitalization for bleeding, transfusion).ResultsThe COMPASS‐eligible population comprised 5.142 patients with ischemic and bleeding outcome of 2.3 (2.1–2.5) and 0.5 (0.4–0.6) per 100 patient‐years, respectively. Patients with intermediate REACH RIS (n = 1934 [37.6%]) had the higher ischemic risk (3.0 [2.6–3.4]) with similar bleeding risk (0.5 [0.4–0.7]) as the overall population. Patients with low CHA₂DS₂VaSc (n = 229 [4.4%]) had a very low ischemic risk (0.6 [0.3–1.3]) with similar bleeding risk (0.5 [0.2–1.1]).ConclusionsIntermediate REACH RIS identified potential optimal candidates for adjunction of low‐dose rivaroxaban while patients with low CHA₂DS₂VaSc score .appears unlikely to benefit from the COMPASS regimen. None of the three risk scores predicted the occurrence of serious bleeding.     

大鼠血浆中利伐沙班的LC-MS/MS法测定及其药动学

建立了液相色谱-串联质谱法测定大鼠血浆中的利伐沙班(1).采用C18色谱柱,以艾瑞昔布(2)为内标,乙腈∶10 mmol/L乙酸铵溶液(用甲酸调至pH 3.14) (50∶50)为流动相,ESI源正离子检测方式,多反应监测,监测离子对m/z 436.2→m/z 145.2 (1),m/z 370.1→m/z 278.0(2).SD大鼠经口灌胃给予1,主要药动学参数分别为:Cmax(438.19±122.02) ng/ml,tmax(0.69±0.20)h,AUC0→24h(1 692.75±654.72) ng·h·ml-1,AUC0→∞(1 760.25±649.11)ng·h·ml-1,t1/2 (3.46±1.10)h.     

Periprocedural management of rivaroxaban-treated patients

Introduction: The increasing and widespread use of direct oral anticoagulants (DOACs) demands guidelines and experts’ consensus for their rational and safe use, especially in certain situations for which there is no evidence-based consensus, such as the periprocedural setting. Rivaroxaban is an oral factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF) and for treatment and prevention of venous thromboembolism (VTE) in major orthopedic surgery. This article is addressed to all the clinicians involved in the periprocedural approach of patients treated with rivaroxaban, with the aim to give practical recommendations to improve patients’ management during and after surgery.

Areas covered: This article is based on a consensus of specialists involved in anticoagulant treatment and in periprocedural setting, including experts in thrombosis, cardiologists, internists, clinical pathologists and anesthesiologists. The authors performed a review of the literature and expressed statements based on the results of the review as well as on personal experience.

Expert opinion: Rivaroxaban is a safe and effective drug that simplifies management of anticoagulation also in patients undergoing invasive procedures. However, periprocedural management could be challenging and physicians must carefully balance the risk of bleeding and the risk of thrombosis.     

Pharmacotherapy with oral Xa inhibitors for venous thromboembolism

Introduction: Venous thromboembolism (VTE) causes substantial morbidity and mortality worldwide. The traditional treatment of VTE, with an initial therapy with (low molecular weight) heparin or fondaparinux and a continued treatment with vitamin K antagonists, is effective but has limitations.

Areas covered: The current review summarizes the results of the Phase III trials with the new oral direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban and provides a meta-analysis of these trials in the subgroups of elderly patients (> 75 years) and patients with impaired renal function.

Expert opinion: The practical use of direct Xa inhibitors in the treatment of VTE in general and in specific subgroups is discussed. For elderly patients, patients with extremes of body weight, cancer patients or patients with moderate renal impairment, pooled data suggest that the direct oral Xa inhibitors are a reasonable alternative to standard therapy. For other indications, such as treatment of VTE in children, during pregnancy or in the context of heparin-induced thrombocytopenia, further data from clinical trials are needed.     

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial fibrillation: a Bayesian meta-analysis approach

Introduction: Choosing between different non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult due to the absence of head to head comparative studies. We performed a Bayesian meta-analysis to explore similarities and differences between different NOACs and to rank treatments overall for safety and efficacy outcomes.

Areas covered: Through a systematic literature search we identified randomized controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban versus adjusted-dose warfarin in patients with NVAF.

Expert opinion: Warfarin ranked worst for all-cause mortality and intracranial bleedings and had a nil probability of ranking first for any outcome. The risk of major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and both doses of edoxaban. All agents reduced the risk of intracranial bleeding versus warfarin. Edoxaban 30 mg was the best among the treatments being compared for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for stroke and systemic embolism. This study suggests that NOACs are generally preferable to warfarin in patients with NVAF. However, safety and efficacy differences do exist among NOACs, which might drive their use in specific subsets of AF patients, allowing prescribers to tailor treatment to distinct patient profiles.     

Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to investigate the effects of rivaroxaban on left ventricle thromboprophylaxis in patients with anterior ST-segment elevation myocardial infarction (STEMI).BackgroundAnterior STEMI is associated with an increased risk of left ventricular thrombus (LVT) formation. The contemporary role of prophylactic rivaroxaban therapy remains unclear.MethodsWe randomly assigned 279 patients with anterior STEMI who had undergone primary percutaneous coronary intervention to receive, in a 1:1 ratio, low-dose rivaroxaban (2.5 mg twice daily for 30 days) and dual antiplatelet therapy (DAPT) or only DAPT. The primary efficacy outcome was the LVT formation within 30 days. Net clinical adverse events were assessed at 30 days and 180 days, including all-cause mortality, LVT, systemic embolism, rehospitalization for cardiovascular events, and bleeding.ResultsThe addition of low-dose rivaroxaban to DAPT reduced LVT formation within 30 days compared with only DAPT (0.7% vs 8.6%; HR: 0.08; 95% CI: 0.01-0.62; P = 0.015; P < 0.001 for superiority). Net clinical adverse events were lower within 30 days in the rivaroxaban group versus those in the only DAPT group and remained relatively low throughout the follow-up period. There were no significant differences in bleeding events between the 2 groups in 30 days and 180 days. However, 1 case of intracranial hemorrhage (major bleeding) occurred in the rivaroxaban group within 30 days.ConclusionsOur results supported that the short-duration addition of low-dose rivaroxaban to DAPT could prevent LVT formation in patients with anterior STEMI following primary percutaneous coronary intervention. A larger multiple-institution study is necessary to determine the generalizability.     

利伐沙班对胸腰椎骨折患者术后静脉血栓栓塞的预防效果

目的探讨利伐沙班对胸腰椎骨折患者术后预防静脉血栓栓塞症（VTE）的临床疗效及安全性。方法以喀什地区第一人民医院收治的胸腰椎骨折100例患者为研究对象,随机分为两组：试验组50例（术后服用利伐沙班）;对照组50例（皮下注射低分子量肝素）。在术前和术后14 d 进行随访,根据彩超观察 VTE 的发生情况。结果试验组术后 VTE 的发生率为8％低于对照组（18％,P＜0．05）;试验组总的出血事件发生率为6％（大出血1例,非大出血2例）稍微高于对照组总的4％（非大出血2例,无大出血,P ＞0．05）;试验组平均引流量[（365．6±181．4）mL]高于对照组[（300．7±108．2）mL ,P＜0．05];术后10 d 比较两组患者凝血系统变化差异无统计学意义（P＞0．05）。结论应用利伐沙班预防胸腰椎骨折患者术后 VTE 安全、有效。