rivaroxaban and Postoperative-Complications

To evaluates the efficacy and safety of rivaroxaban versus aspirin in prevention of venous thromboembolism (VTE) following total hip (THA) or knee arthroplasty (TKA) or hip fracture surgery.. Major databases were systematically searched for all relevant studies published in English up to October 2020. The meta-analysis was conducted using RevMan 5.3 software.. In total, 7 studies were retrieved which contained 5133 patients. Among these patients, 2605 patients (50.8%) received rivaroxaban, whereas 2528 patients (49.2%) received aspirin. There were no statistical difference between aspirin and rivaroxaban for reducing VTE (RR = 0.75, 95% CI 0.50-1.11, I. There was no significant difference between aspirin and rivaroxaban in prevention of venous thromboembolism following total joint arthroplasty or hip fracture surgery. Aspirin may be an effective, safe, convenient, and cheap alternative for prevention of VTE. Further large randomized studies are required to confirm these findings.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Fracture Fixation, Internal; Hip Fractures; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Pregnancy is a known risk factor for spontaneous spinal epidural hematoma. During cesarean section or vaginal delivery, the unstable hemodynamic status that may occur owing to fluctuation of intra-abdominal pressure increases the possibility of spontaneous spinal epidural hematoma. During labor and the postpartum period, neurologic symptoms may be masked by labor pain or anesthesia block, which makes early diagnosis difficult, especially in the obstetric clinic without a neurologist or neurosurgeon.. A 28-year-old woman who had a normal spontaneous delivery under epidural anesthesia developed bilateral lower limb flaccid paralysis and loss of sensation 12.5 hours after delivery. Magnetic resonance imaging showed a 5.2 × 0.9 × 2 cm spinal epidural hematoma with severe spinal cord stenosis at the T2-T5 level with no evidence of a vascular anomaly. After emergent evacuation of the spinal epidural hematoma, lower limb muscle power improved from 0/5 to 1/5, and sensation gradually returned to bilateral lower limbs 22 days postoperatively. Deep vein thrombosis developed at 35 days postoperatively, and an inferior vena cava filter was implanted with urokinase infusion for thrombolytic therapy. She was discharged on day 52 after admission, and lower limb muscle power returned to normal after 3 months.. Clinicians should observe postpartum women for signs of myelopathy or back tenderness and closely monitor neurologic function until anesthesia has run its course. A prompt diagnosis can enable prompt intervention.

Topics: Adult; Analgesia, Epidural; Anesthesia, Epidural; Decompression, Surgical; Delivery, Obstetric; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hematoma, Epidural, Spinal; Humans; Hypesthesia; Laminectomy; Lower Extremity; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Paraplegia; Postoperative Complications; Pregnancy; Puerperal Disorders; Recovery of Function; Rivaroxaban; Spinal Cord Compression; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator; Vena Cava Filters; Venous Thrombosis

Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007.. To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA.. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019.. We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status.. Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence.. This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GC. There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.

Topics: Adult; Anticoagulants; Arthroscopy; Aspirin; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Knee Joint; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Stockings, Compression; Venous Thrombosis

Decisions surrounding periprocedural anticoagulation management must balance thromboembolic and procedural bleed risk. The interruption of both warfarin and DOACs requires consideration of anticoagulant pharmacokinetics, procedural bleed risk and patient characteristics. There is a diminishing role for periprocedural bridging LMWH overall and no role for bridging LMWH for the procedural interruption of DOACs. A clinical approach to perioperative DOAC management based on operative bleeding risk and renal function is safe and effective, and at present, is preferred over preprocedural DOAC levels testing. Clear communication of the anticoagulation interruption plan to both the patient and the patient's care team is essential.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Perioperative Care; Postoperative Complications; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Stroke; Surgical Procedures, Operative; Warfarin

The application of venous thromboembolism (VTE) prophylaxis has been the topic of intense debate in plastic surgery. The overall incidence of VTE is low in plastic surgery patients as compared to other surgical subspecialties but may be higher in the inpatient rather than outpatient plastic surgery populations. The Caprini Risk Assessment Model is the most highly studied and validated tool to assess VTE risk in plastic surgery patients. However, the Caprini model lacks procedure-specific risk assessment and patient-specific risk factor calculations. Due to these limitations, such as the low incidence and the heterogeneous nature of the specialty, trials lacked the power to capture proof of benefit, except in the highest-risk inpatient population. The emerging use of aspirin and novel oral anticoagulants may provide an alternative, as noninferiority in terms of efficacy and safety has been demonstrated in other fields. In this review, the authors intend to summarize the current state of evidence for prevention and explore the modalities available for prophylaxis, including novel oral anticoagulants.

Topics: Administration, Oral; Anticoagulants; Aspirin; Chemoprevention; Heparin, Low-Molecular-Weight; Humans; Incidence; Plastic Surgery Procedures; Postoperative Complications; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Prophylactic anticoagulant therapy is recommended to reduce the risk of venous thromboembolism (VTE) after total hip or knee arthroplasty, and has become the standard of care. Rivaroxaban is a novel oral medication that directly inhibits factor Xa for the prevention and treatment of thromboembolic conditions.. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the efficacy and safety of rivaroxaban after total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgery. We reviewed several databases including PubMed, the Cochrane Library, Embase and the US trial registry to detect appropriate RCTs for our meta-analysis. The primary efficacy outcome of this meta-analysis was the combination of any deep-vein thrombosis (DVT), non-fatal pulmonary embolism (PE), and death from any cause. The main safety outcome was bleeding events which included significant bleeding events, clinically relevant insignificant bleeding events, or minor events. Other end points were the number of patients who received blood transfusion the volume of transfused whole blood or red blood cells, and the volume of postoperative drainage.. Thirteen RCTs were included in this meta-analysis. This meta-analysis showed that the overall rate of VTE events, DVT, PE, and death were 1%, 6%, < 1% and < 1%, respectively, for patients receiving treatment with rivaroxaban after THA and TKA surgery. The subgroup analysis demonstrated rivaroxaban had more superior effects in THA patients. The pooled analysis of bleeding events showed that the overall rate of major bleeding events, overt bleeding events associated with fall in Hb of > 2 g/DL, clinically overt bleeding events leading to transfusion of > 2 units of blood, clinically overt bleeding events leading to further surgeries, and non-major bleeding events were < 1%, < 1%, < 1%, < 1%, and 3%, respectively.. This is the first systematic review of the literature providing incidence of efficacy and safety outcomes for thromboprophylaxis in THA and TKA patients. Moreover, this meta-analysis showed that rivaroxaban had more superior effect in THA patients.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Total knee arthroplasty is an elective procedure performed on relatively healthy individuals. However, due to the inherent risk of venous thromboembolism, drugs are used for its prophylaxis. The objective of the present study was to conduct a systematic review of the literature to compare the efficacy of enoxaparin and rivaroxaban in preventing this complication and the risk of intraoperative bleeding. We reviewed the SciELO, Pubmed and Cochrane databases with the descriptors knee arthroplasty, rivaroxaban and enoxaparin through the PICO search strategy. Inclusion criteria were the articles during the study period comparing both drugs in knee arthroplasty. Relevant criteria to study eligibility were articles published since 2010 and with a sample of more than 20 patients; studies obtained in their entirety; and studies with follow-up of more than 12 months. The variables used to compare the articles were the most common postoperative complications of knee arthroplasties: venous thromboembolism and bleeding. We used the Review Man software, version 5.3, for structuring the review. In the studies analyzed, considering symptomatic venous thromboembolism, rivaroxaban resulted in higher benefits when compared to enoxaparin.. A artroplastia total do joelho é um procedimento eletivo, realizado em indivíduos relativamente saudáveis. Porém, devido ao risco inerente de tromboembolismo venoso, são utilizados fármacos para sua profilaxia. O objetivo do presente trabalho foi conduzir uma revisão sistemática da literatura para comparar a eficácia da enoxaparina e da rivaroxabana na prevenção desta complicação e no risco de sangramento intraoperatório. Foi feita uma revisão no site SciELO, Pubmed e Cochrane através dos descritores, artroplastia de joelho, rivaroxabana e enoxaparina através da estratégia de busca PICO. Os critérios de inclusão foram os artigos no período estudado, que comparavam ambas as drogas em cirurgias de artroplastia do joelho. Os critérios de relevância para tornar o estudo elegível foram definidos como: somente artigos publicados a partir 2010 e com casuística com mais de 20 pacientes foram considerados; somente estudos obtidos em sua íntegra foram analisados; somente estudos com seguimento maior do que 12 meses foram considerados relevantes. As variáveis utilizadas para a comparação dos artigos foram as complicações mais comuns no pós-operatório de artroplastias do joelho: tromboembolismo venoso e sangramento. Foi utilizado o Review Man 5.3 para estruturação da revisão. Os autores observaram que nos estudos analisados, considerando tromboembolismo venoso sintomático, a rivaroxabana resultou em maiores benefícios quando comparada com a enoxaparina.

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Enoxaparin; Humans; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Currently there is significant variation in the management of venous thromboembolism prophylaxis following total knee arthroplasty (TKA). Excessive wound ooze and bleeding is thought to increase a patient's risk of haematoma formation and possible infection. We evaluated the rate of unexpected reoperation in the perioperative period in patients who received aspirin, rivaroxaban or enoxaparin following primary TKA.. A systematic literature search was conducted in MEDLINE, CENTRAL and Embase to identify patients who underwent primary TKA. Two researchers independently reviewed the references identified in the literature search. The final 11 studies included for review were published between 1996 and 2016.. There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. Of the 5141 patients treated with enoxaparin, 11 (0.21%) required reoperation; of the 2764 patients treated with rivaroxaban, 12 (0.43%) required reoperation; and of the 228 patients treated with aspirin, seven (3.07%) required reoperation. The average time to follow-up in the 11 studies was 55 days, ranging from 30 to 180 days post-operatively.. There was a higher rate of reoperation in patients treated with aspirin following TKA when compared to enoxaparin and rivaroxaban in the perioperative period. While there is extensive data on the safety and efficacy of these medications following joint arthroplasty, improved reporting of surgically relevant outcomes are needed to assist both the surgeon and patient in clinical decision-making.

Topics: Arthroplasty, Replacement, Knee; Aspirin; Australia; Case-Control Studies; Clinical Decision-Making; Enoxaparin; Factor Xa Inhibitors; Heparin, Low-Molecular-Weight; Humans; Perioperative Period; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Reoperation; Rivaroxaban; Safety; Treatment Outcome; Venous Thromboembolism

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Stroke; Thiazoles; Venous Thromboembolism; Withholding Treatment

To assess the incremental benefit of uninterrupted direct oral anticoagulants (DOACs) vs. uninterrupted vitamin K antagonists (VKA) for catheter ablation (CA) of non-valvular atrial fibrillation (NVAF) on three primary outcomes: major bleeding, thrombo-embolic events, and minor bleeding. A secondary outcome was post-procedural silent cerebral infarction (SCI) as detected by brain magnetic resonance imaging.. A systematic review of Medline, Cochrane, and Embase was done to find all randomized controlled trials (RCTs) in which uninterrupted DOACs were compared against uninterrupted VKA for CA of NVAF. A fixed-effect model was used, with the exception of the analysis regarding major bleeding events (I2 > 25), for which a random effects model was used. The benefit of uninterrupted DOACs over VKA was analysed from four RCTs that enrolled a total of 1716 patients (male: 71.2%) with NVAF. Of these, 1100 patients (64.1%) had paroxysmal atrial fibrillation. No significant benefit was seen in major bleeding events [risk ratio (RR) 0.54, 95% confidence interval (95% CI) 0.29-1.00; P = 0.05]. No significant differences were found in minor bleeding events (RR 1.11, 95% CI 0.82-1.52; P = 0.50), thrombo-embolic events (RR 0.74, 95% CI 0.26-2.11; P = 0.57), or post-procedural SCI (RR 1.06, 95% CI 0.74-1.53; P = 0.74).. An uninterrupted DOACs strategy for CA of NVAF appears to be as safe as uninterrupted VKA without a significantly increased risk of minor or major bleeding events. There was a trend favouring DOACs in terms of major bleeding. Given their ease of use, fewer drug interactions and a similar security and effectiveness profile, DOACs should be considered first line therapy in patients undergoing CA for NVAF.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Cerebral Infarction; Dabigatran; Drug Administration Schedule; Factor Xa Inhibitors; Hemorrhage; Humans; Postoperative Complications; Postoperative Hemorrhage; Risk Factors; Rivaroxaban; Severity of Illness Index; Thromboembolism; Warfarin

Topics: Anticoagulants; Aspirin; Clopidogrel; Drug Synergism; Drug Therapy, Combination; Factor Xa Inhibitors; Hemorrhage; Humans; Mortality; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Rivaroxaban; Stents; Stroke; Thrombophilia; Ticlopidine

This article analyzed the clinical efficacy and tolerability of rivaroxaban and enoxaparin in patients undergoing total knee arthroplasty (TKA) surgery.. Five randomized, controlled clinical trials on rivaroxaban versus enoxaparin in patients who underwent TKA were identified and included in this meta-analysis.. The meta-analysis indicated that rivaroxaban prophylaxis was associated with lower rates of symptomatic venous thromboembolism (VTE) (relative risk[RR]:0.55; 95% confidence interval [CI]: 0.35-0.86; P = .009), symptomatic deep vein thrombosis (DVT) (RR 0.44, 95% CI 0.25-0.80, P = .007), asymptomatic DVT (RR: 0.57; 95% CI: 0.37-0.89; P = .01), distal DVT (RR: 0.62; 95% CI: 0.45-0.85; P = .003) and proximal DVT (RR: 0.42; 95% CI: 0.24-0.75; P = .004). Compared with the enoxaparin group, the incidence of symptomatic pulmonary embolism (PE) (RR: 0.48; 95% CI: 0.19-1.24; P = .13) in the rivaroxaban group was not significantly different. A nonsignificant trend towards all-cause death (RR: 0.38; 95% CI: 0.03-4.92; P = .46) or major bleeding (RR: 1.59; 95% CI: 0.77-3.27; P = .21) risk between rivaroxaban and enoxaparin prophylaxis was found.. Compared with the enoxaparin group, the group using rivaroxaban after TKA had a significantly lower rate of symptomatic VTE, symptomatic DVT, asymptomatic DVT, distal DVT, and proximal DVT. Our study shows that rivaroxaban after TKA is more effective than enoxaparin and did not increase major bleeding or all-cause mortality.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Humans; Male; Middle Aged; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Anticoagulants; Dabigatran; Humans; Perioperative Period; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thromboembolism

After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients.. After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included.. The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects.. Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding.

Topics: Anticoagulants; Arthroplasty; Azetidines; Benzylamines; Dabigatran; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Treatment Outcome; Venous Thromboembolism; Warfarin

A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?' Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The novel oral anticoagulant agents (NOACs) assessed in the included studies were dabigatran (a direct thrombin inhibitor) and rivaroxaban (a Factor Xa inhibitor). Dabigatran was included in all five studies and showed bleeding complication rates of 0-4%. Rivaroxaban was included in one study and had bleeding complication rates of 4%. Warfarin was a comparator agent in three studies and had bleeding complication rates of 4.6-8%. The incidence rate of thromboembolic complications was 0-1% with dabigatran and 0% with rivaroxaban and warfarin in all studies. Based on the available studies, there is no evidence of significantly increased risk of bleeding or thromboembolic events with NOACs compared with warfarin when used at the time of cardiac rhythm device implantation. However, not all patients in the studies were actually receiving the specified NOAC at the time of device implantation, thereby limiting the available evidence.

Topics: Aged, 80 and over; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Defibrillators, Implantable; Humans; Intraoperative Complications; Male; Pacemaker, Artificial; Postoperative Complications; Rivaroxaban; Thromboembolism; Warfarin

The aim of this network meta-analysis was to evaluate the comparative efficacy and safety of dabigatran, rivaroxaban, apixaban, interrupted vitamin K antagonist (I-VKA), and continuous VKA (C-VKA) in patients undergoing radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF).. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify clinical trials comparing dabigatran, rivaroxaban, or apixaban with I-VKA or C-VKA, or against each other, in AF patients undergoing RFCA. A network meta-analysis was conducted to directly and indirectly compare the efficacy and safety of competitive anticoagulation regimens with a Bayesian random-effects model.. A total of 39 studies enrolling 27,766 patients were included. C-VKA demonstrated significant superiority over I-VKA in reducing thromboembolic events (risk difference [RD] -0.0068, 95 % confidence interval [CI] -0.0106 to -0.0032) and major bleeding complications (RD -0.0044, 95 % CI -0.0098 to -0.0006). Rivaroxaban compared with I-VKA was associated with a lower risk of thromboembolism (RD -0.0073, 95 % CI -0.0134 to -0.0012), being at the best ranking position among all of the compared anticoagulation regimens in terms of both the efficacy and safety. None of the remaining comparisons reached statistically significant difference in the rate of thromboembolism or major bleeding.. The present study suggests that C-VKA is superior to I-VKA for AF patients undergoing RFCA. Rivaroxaban is the highest probability to be the optimal alternative to C-VKA among the three non-VKA oral anticoagulants in AF ablation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Causality; Comorbidity; Dabigatran; Female; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thromboembolism; Treatment Outcome; Vitamin K

Topics: Anticoagulants; Dabigatran; Humans; Postoperative Complications; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Surgical Procedures, Operative

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.. 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.. 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.

Topics: Administration, Oral; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Perioperative Period; Postoperative Complications; Risk; Rivaroxaban; Surgical Procedures, Operative; Thiophenes; Thromboembolism

The incidence of post-operative arterial thrombosis (AT) (acute myocardial infarction [AMI] and ischaemic stroke) is increased in patients undergoing total hip replacement (THR) or total knee replacement (TKR). We compared the incidence of post-operative AT in non-vitamin K antagonist oral anticoagulants (NOACs)-treated and enoxaparin-treated patients, performing a systematic review of phase III randomised controlled trials (RCTs) of venous thromboembolism (VTE) prophylaxis in THR and TKR. Studies were identified by electronic search of MEDLINE and EMBASE database until July 2014. Differences between NOACs and enoxaparin groups in the efficacy and safety outcomes were expressed as odds ratios (ORs) with pertinent 95 % confidence intervals (95 % CI). Statistical heterogeneity was assessed with the I² statistic. Eleven phase III RCTs for a total of 31,319 patients were included. Patients underwent TKR in six studies and THR in five studies. The NOACs under study were dabigatran (four studies), apixaban (three studies) and rivaroxaban (four studies). AT occurred in 0.23 % of patients on NOACs and in 0.27 % of patients on enoxaparin: the OR at fixed-effect model was 0.86 (95 % CI 0.53-1.40; I² 11 %). No differences in AT incidence among the three NOACs were observed. The incidence of major and clinically relevant bleeding was similar in NOACs and enoxaparin groups (OR 1.03, 95 % CI 0.92-1.15; I² 38 %). In conclusion, in RCTs of pharmacological VTE prophylaxis in patients undergoing THR or TKR, there was no difference in the incidence of post-operative AT among patients treated with NOACs, compared to those treated with enoxaparin.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Brain Ischemia; Clinical Trials, Phase III as Topic; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Female; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Postoperative Complications; Postoperative Hemorrhage; Prothrombin; Pulmonary Embolism; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome

The aim of this study is to compare effectiveness and safety profile of rivaroxaban with bemiparin in 3-week extended prophylaxis after knee arthroscopy.. Four hundred and sixty-seven patients were included in this review divided in two groups. One followed prophylaxis with rivaroxaban and the other one with bemiparin. All patients were interviewed and explored at 1 and 3 months postoperatively, looking for symptomatic signs of deep-vein thrombosis (DVT). In case of suspicion, diagnostic tests were performed. Collected data were age, sex, gender, diagnosis, time with ischemia, body mass index, concomitant diseases, concomitant therapy, DVT signs, treatment satisfaction, minor and major complications, treatment adherence and tolerability.. No thromboembolic events were observed in any of the groups. In one case treated with rivaroxaban, the drug had to be withdrawn due to epistaxis.. Our study showed that extended prophylaxis with 10 mg of rivaroxaban once daily for 3 weeks resulted as effective as bemiparin in knee arthroscopy thromboprophylaxis.

Topics: Adult; Aged; Arthroscopy; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Knee Joint; Male; Middle Aged; Morpholines; Polypharmacy; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Risk Factors; Rivaroxaban; Therapeutic Equipoise; Thiophenes; Thrombophilia; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Emergencies; Factor Xa Inhibitors; Hemorrhage; Humans; Kidney Diseases; Morpholines; Orthopedic Procedures; Postoperative Complications; Premedication; Pyrazoles; Pyridines; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

Topics: Acute Coronary Syndrome; Adenosine; Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Hemorrhage; Humans; Morpholines; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Postoperative Complications; Prasugrel Hydrochloride; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis; Ticagrelor

Heparins and vitamin K antagonists (VKA) used commonly are the standard treatment of venous and arterial thromboses. They are very efficient and safe, but have some limitations: iatrogenicity, laboratory monitoring, parenteral use for heparins and fondaparinux. Nowadays, four new inhibitors of factor Xa are used orally (rivaroxaban, apixaban, edoxaban, betrixaban), and they are at least as efficient as heparins and vitamin K antagonists. The objective is to substitute these indirect inhibitors of factor Xa (heparins, low molecular weight heparins and fondaparinux) in the prevention of venous and arterial thromboembolic episodes. The new direct inhibitors do not require routine laboratory monitoring of blood coagulation. They inhibit the extrinsic and the intrinsic pathways of blood coagulation. Rivaroxaban and apixaban are efficacious and safe in the prevention of cerebral infarcts in patients with non-valvular fibrillation. Apixaban is another direct inhibitor of factor Xa used orally which is developed in the same indications as rivaroxaban. Edoxaban and betrixaban are also in development. The objective of this work is to study the pharmacodynamic, pharmacokinetic, the efficacy and safety of these four oral direct factor Xa inhibitors.

Topics: Acute Coronary Syndrome; Administration, Oral; Anticoagulants; Benzamides; Blood Coagulation; Embolism; Factor Xa Inhibitors; Hemorrhage; Hemostatics; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Thiophenes; Thrombophilia; Thrombosis

Topics: Administration, Oral; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Gastrointestinal Hemorrhage; Humans; Intracranial Embolism; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Thiophenes; Thrombosis; Vitamin K; Warfarin

EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Recognize the high risk of postoperative venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. 2. Distinguish the different pharmacological mechanisms of VTE prophylaxis drugs. 3. Delineate the advantages and disadvantages of each VTE prophylaxis drug. 4. Recognize that rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage. Patients undergoing major orthopedic surgery are at high risk for developing postoperative venous thromboembolism (VTE). The authors analyzed the available evidence on the efficacy and safety of dabigatran, apixaban, and rivaroxaban vs low-molecular-weight heparins (LMWHs) as VTE prophylaxis in major orthopedic surgery. Outcomes evaluated included total VTE, deep venous thrombosis (DVT), pulmonary embolism (PE), death, and major bleeding. Rivaroxaban and apixaban are more efficacious than dabigatran and are as safe as dabigatran. Rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage.

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Dabigatran; Heparin, Low-Molecular-Weight; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Until recently, warfarin had been one of the only treatment options for long-term anticoagulation of patients with atrial fibrillation, venous thromboembolism, or other medical conditions that require chronic anticoagulation. A main concern when treating patients with anticoagulants is balancing the benefits of preventing a thromboembolic event with the risks of bleeding events. The US Food and Drug Administration recently approved 2 new oral anticoagulants, dabigatran and rivaroxaban, for stroke prevention in patients with atrial fibrillation, and is currently reviewing a drug application for a third new oral anticoagulant, apixaban. These new anticoagulants do not require strict and frequent laboratory monitoring, dosing adjustments, or dietary restrictions, and they incur fewer drug-drug interactions than warfarin. However, these new medications do not have specific reversal agents, may require dosage adjustment based on patient renal function, and lack clinical data regarding their long-term safety and efficacy. The 2012 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for antithrombotic therapy and prevention of thrombosis include recommendations for dabigatran, rivaroxaban, and apixaban for certain indications. Each of the 3 novel oral anticoagulants has specific pharmacokinetic and pharmacodynamic properties that may make them suitable agents for use in specific patient populations. Knowledge of dosing, drug-drug interactions, monitoring parameters, and clinical considerations for each of these new medications will help clinicians decide for which patients they may be best suited to replace conventional therapy with warfarin.

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Dabigatran; Drug Administration Schedule; Humans; Morpholines; Postoperative Complications; Practice Guidelines as Topic; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism is a common cause of morbidity and mortality among patients undergoing elective orthopedic surgery. Due to the high incidence of venous thromboembolism in this setting, perioperative anticoagulation is the recommended approach for thromboprophylaxis. Low molecular weight heparin (LMWH), fondaparinux and warfarin are the agents commonly used for thromboprophylaxis. The well-recognized limitations of warfarin and the inconvenience and discomfort associated with the subcutaneous administration of low molecular weight heparin and fondaparinux inspired intense investigation to develop novel oral anticoagulants (NOACs) with more predictable pharmacokinetics, fewer drug interactions and no need for regular laboratory monitoring. Three NOACs have been demonstrated to be effective for thromboprophylaxis after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in large randomized controlled trials. Here we review the pharmacology of rivaroxaban, dabigatran, and apixaban, summarize the major clinical trials of these agents in thromboprophylaxis after THA and TKA, and discuss the clinical factors to be considered by providers when selecting a NOAC for their patients.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Within the past 5 years, the oral anticoagulants rivaroxaban, apixaban, and dabigatran etexilate have been approved for the prevention of venous thromboembolism in adult patients after elective hip or knee arthroplasty in the European Union and many other countries worldwide. These agents differ from the previously available anticoagulants because they selectively and directly inhibit a single factor in the coagulation cascade-rivaroxaban and apixaban inhibit Factor Xa, and dabigatran inhibits Factor IIa (thrombin)-potentially enhancing the predictability of their anticoagulant effect. Currently, although some guidelines provide recommendations for the use of rivaroxaban, dabigatran etexilate, and apixaban in clinical practice, there are still questions regarding the optimal practical management of patients receiving these agents. This article briefly reviews the practical limitations associated with conventional anticoagulants, discusses potential issues with the practical management of the newer oral anticoagulants, and provides clinical experience from a single institution where rivaroxaban and dabigatran etexilate have been used within their approved indications.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Blood Coagulation Tests; Clinical Trials, Phase III as Topic; Contraindications; Dabigatran; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Hematoma, Epidural, Spinal; Humans; Morpholines; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Hemorrhage; Postoperative Nausea and Vomiting; Practice Guidelines as Topic; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Patients undergoing a total hip or total knee arthroplasty are at high risk of thromboembolism in the postoperative period and after hospital discharge; consequently, clinical guidelines recommended thromboprophylaxis for 10-35 days. Although improved surgical techniques and widespread use of anticoagulants have substantially reduced the incidence of thromboembolic events, venous thromboembolic disease is still a dangerous complication and, in these patients, pulmonary embolism remains the main cause of death. Low molecular weight heparins have long been the mainstay of prevention. However, parenteral administration is inconvenient for many patients, which can sometimes cause poor treatment adherence. In recent years, a new class of oral, fixed-dose anticoagulants, with different mechanisms of action, few interactions and a predictable effect, has been developed. At present, a thrombin inhibitor (dabigatran) and two FXa inhibitors (rivaroxaban and apixaban) are available for prophylaxis in patients after total knee or total hip arthroplasty. In several phase III clinical trials, these drugs have been shown to have equal or superior efficacy and a similar degree of safety to conventional therapy with enoxaparin. These new drugs can significantly improve long-term prevention, particularly in the community setting.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Morpholines; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Direct experimental safety comparisons of Xa coagulation factor direct inhibitors, apixaban and rivaroxaban, on their approved therapeutic indications have not been identified. Due to recently raised safety concerns, a meta-analysis was carried out pooling data from studies identified on a Medline and Cochrane Library search in order to better evaluate the safety profile of both drugs. Abstracts from scientific meetings were also searched from 2003 to 2011. Primary and secondary outcome measures were major bleeding and total bleeding, respectively. Relative risks (RRs) were estimated using random effects models and statistical heterogeneity was estimated with I(2) statistics. Of the 160 screened publications, 12 clinical trials were included in which enoxaparin was the active control. For knee arthroplasty, apixaban was associated with significantly fewer major bleeding events (6496 patients, RR 0.56, 95% confidence interval [CI] 0.32-0.96) and fewer total bleeding events (6496 patients, RR 0.81, 95% CI 0.67-0.97). There were no significant differences in the incidence of major bleeding events (5699 patients, RR 1.40, 95% CI 0.56-3.52) or in the incidence of total bleeding events for rivaroxaban (5699 patients, RR 1.09, 95% CI 0.91-1.30). No differences were found when thromboprophylaxis after hip replacement was the case. Apixaban seems to be associated with a lower risk of the incidence of hemorrhagic events after total knee arthroplasty. For hip arthroplasty, no differences were found between the studied drugs.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thrombosis

Rivaroxaban (Xarelto®), an oral oxazolidinone-based anticoagulant, is a potent, selective, direct inhibitor of factor Xa that is used in the prevention of venous thromboembolism (VTE) in adult patients after total hip replacement (THR) or total knee replacement (TKR) surgery. In large, clinical trials, oral rivaroxaban 10 mg once daily was more effective than subcutaneous enoxaparin 40 mg once daily in preventing postoperative VTE in patients undergoing THR or TKR surgery. Rivaroxaban was associated with significantly lower incidences of the primary endpoint, total VTE (composite of deep vein thrombosis, non-fatal pulmonary embolism, or death from any cause) compared with enoxaparin regimens across all studies. For example, in the largest trial in patients undergoing THR, total VTE occurred in 1.1% of rivaroxaban recipients and 3.7% of enoxaparin recipients (absolute risk reduction 2.6% [95% CI 1.5, 3.7]) in the modified intent-to-treat population. Notably, the greater efficacy of rivaroxaban was achieved without a significant increase in the incidence of major bleeding episodes compared with enoxaparin; bleeding events were the most frequently reported adverse events across clinical trials. Pyrexia, vomiting, nausea, and constipation were the most frequently reported of the non-bleeding treatment-emergent adverse events in rivaroxaban recipients and occurred at a similar rate to that with enoxaparin treatment. In addition, preliminary pharmacoeconomic analyses in Canada and the US indicate that rivaroxaban is a cost-saving treatment strategy versus enoxaparin. Although the position of rivaroxaban relative to other therapies remains to be fully determined, it is an effective option for the prophylaxis of VTE following THR and TKR.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of "all VTE and all-cause death" were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.

Topics: Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Female; Hemorrhage; Humans; Male; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.. We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.. Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).. Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.

Topics: Anticoagulants; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis

The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Biological Availability; Clinical Trials as Topic; Dabigatran; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Postoperative Complications; Prothrombin; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

Thromboprophylaxis in orthopedic surgery remains a controversial issue despite recent changes to NICE guidelines, particularly with the addition of oral factor Xa inhibitors. The healthcare burden of venous thromboembolism is substantial and needs frequent academic and clinical appraisal.. The authors review the available relevant literature on the use of rivaroxaban in orthopedic surgery, identified using an EMBASE (1980 - 2010) and Ovid MEDLINE (1950 - 2010) search of published articles up to August 2010. This includes clinical studies, case reports and experimental studies where applicable. Search terms include: 'rivaroxaban', 'safety', 'efficacy', 'bleeding', 'toxicity', 'tolerability' and 'complication'.. Rivaroxaban is a safe and effective choice of thromboprophylactic agent following lower limb arthroplasty surgery. More research is required to expand the application of this novel agent to other areas of orthopedic surgery.

Topics: Anticoagulants; Clinical Trials, Phase III as Topic; Humans; Lower Extremity; Morpholines; Orthopedics; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacological strategies, or in cases of contraindications to anticoagulants, as in patients or procedures at high risk of bleeding.

Topics: Aged; Anticoagulants; Antithrombins; Arthroscopy; Bariatric Surgery; Benzimidazoles; Blood Coagulation Disorders, Inherited; Dabigatran; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Hip Fractures; Humans; Kidney; Knee; Laparoscopy; Morpholines; Neoplasms; Orthopedic Procedures; Polysaccharides; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thrombophilia; Venous Thromboembolism

For years, prevention and treatment of thromboembolic events have been restricted to the use of heparins and vitamin K antagonists. These treatments, in spite of their unquestioned efficacy, present numerous limits (hemorrhagic risk, need for regular laboratory controls). These limits call for the development of new antithrombotic drugs. This review briefly reports on three new molecules, in very advanced phases of clinical research: dabigatran (Pradaxa®), rivaroxaban (Xarelto®) and apixaban. These molecules represent new oral anticoagulants, which directly inhibit a coagulation factor (thrombin for dabigatran, factor Xa for rivaroxaban and apixaban) and do not need regular anticoagulant monitoring or dose adjustment. The approval is still restricted in France to the prophylaxis of venous thromboembolism in orthopaedics. Dabigratran will be soon available in the prevention of stroke in atrial fibrillation. With the forthcoming phase III studies to prevent and treat venous thromboembolism, anticoagulant therapy management will be most probably improved in the coming years.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Clinical Trials as Topic; Dabigatran; Drug Approval; Drug Monitoring; Factor Xa Inhibitors; Fibrinolytic Agents; Forecasting; France; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Thrombin; Thromboembolism; Thrombophilia; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Neurosurgical Procedures; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Stockings, Compression; Surgical Procedures, Operative; Thiophenes; Urologic Surgical Procedures; Venous Thrombosis

Vitamin K antagonists and heparins have been standard anticoagulation drugs over the past decades. They are effective and safe but they have several drawbacks which has led to the development of new oral anticoagulants. Dabigatran etexilate is a specific oral thrombin inhibitor and rivaroxaban and apixaban are oral inhibitors of factor Xa. These agents produce a predictable anticoagulant response after fixed-dose administration so that routine coagulation monitoring is unnecessary. Currently, dabigatran etexilate, rivaroxaban and apixaban are licensed for thromboprophylaxis after elective total hip or knee replacement surgery. Since august 2011, dabigatran etexilate is licensed for patients with atrial fibrillation, rivaroxaban will follow. However, indications will be expanded e.g. for therapy of venous thromboembolism. It is important to be aware of the pharmacokinetic and pharmacodynamic profiles of these new agents. The drugs considerably influence the global test of coagulation thus making an interpretation of test results difficult. Currently, there is a lack of suitable coagulation tests to monitor anticoagulation in emergency cases, such as bleeding. Specific antidotes are not yet available.

Topics: Administration, Oral; Antithrombins; Arthroplasty, Replacement, Hip; Atrial Fibrillation; Benzimidazoles; Blood Coagulation Tests; Critical Care; Dabigatran; Drug Approval; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Thrombophilia; Vitamin K

To review the pharmacology, pharmacokinetics, and clinical efficacy/safety profile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery.. A literature search was performed in PubMed/MEDLINE (1966-March 2010), International Pharmaceutical Abstracts (1970-March 2010), and EMBASE (1990-March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets.. All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data.. Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonfatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6-8 hours post-surgery and post-hemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14 days in TKR.. Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.

Topics: Animals; Clinical Trials, Phase III as Topic; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

This study aimed to evaluate the cost-effectiveness of prophylaxis with rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR) from the perspective of the Canadian healthcare system. A model was developed that included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with one-year cycles). Transition probabilities were derived from phase III clinical trials comparing rivaroxaban with enoxaparin and published literature. Costs were derived from the Ontario Case Costing Initiative and publicly available sources. Utilities were derived from published literature. The model reported VTE event rates, quality-adjusted life expectancy and direct medical costs over a five-year horizon. Costs are reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is, rivaroxaban is associated with improved health outcomes as measured by increased quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events (0.0061), and also with lower cost (savings of C$300) per patient. Similarly, rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of 0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five-year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more quality-of-life benefit at a lower cost.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Canada; Cost-Benefit Analysis; Enoxaparin; Follow-Up Studies; Humans; Morpholines; Postoperative Complications; Quality of Life; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Venous Thromboembolism

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.

Topics: Anticoagulants; Antithrombin Proteins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiophenes; Venous Thrombosis; Vitamin K

The traditional agents used for thromboprophylaxis are effective and safe but have limitations particularly related to ease of administration. Newer agents targeting single coagulation factors such as the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban and apixaban have demonstrated efficacy and safety for thromboembolism prophylaxis in the orthopedic population and have the additional benefit of oral administration and predictable pharmacokinetics. Pharmacology of the new anticoagulants and published data on the use of these agents in total knee and hip replacement patients will be reviewed in this article.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiophenes; Venous Thromboembolism

The new oral, antithrombotic drug rivaroxaban is a direct factor Xa inhibitor, which can restrict thrombin generation both in vitro and in vivo. It has a predictable dose-dependent pharmacokinetic and pharmacodynamic profile and is well tolerated. In patients undergoing total hip or knee arthroplasty, rivaroxaban, 10 mg once daily started 6 - 8 h after the operation, had a significantly better antithrombotic efficacy and a comparable safety when compared with enoxaparin. Furthermore in all studies performed the drug had no adverse influence on the liver function in comparison with enoxaparin. In conclusion, rivaroxaban is a potent and safe new compound for antithrombotic prophylaxis in orthopaedic surgery.

Topics: Administration, Oral; Animals; Antithrombin III; Arthroplasty; Clinical Trials as Topic; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Thrombolytic Therapy

Venous thromboembolism is an important complication for patients undergoing surgery. Thromboprophylaxis reduces thromboembolic events.. In this review we discuss the evidence supporting the use of newer agents for thromboprophylaxis, rivaroxaban and dabigatran etexilate. We will also discuss current thromboprophylaxis options for patients undergoing bariatric surgery, including dose and duration of pharmacological prophylaxis and mechanical methods. The most recent The American College of Chest Physicians and American Academy of Orthopedic Surgeons guidelines are also reviewed.. Novel agents may modify our approach to thromboprophylaxis; although these agents offer reduced rates of venographic deep vein thrombosis, their impact on patient important outcomes (clinical deep vein thrombosis, pulmonary embolism and death) requires additional study.

Topics: Benzimidazoles; Dabigatran; Humans; Morpholines; Postoperative Complications; Premedication; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70-79% in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturer's economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban compa

Topics: Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Humans; Morpholines; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Animals; Factor Xa Inhibitors; Heart Diseases; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Thromboembolism; Thrombosis

Currently, pharmacological thromboprophylaxis is frequently required in patients undergoing surgery, due to the high risk of deep venous thrombosis in the perioperative period. The administration of these anticoagulant agents (in Spain, usually low molecular weight heparins or fondaparinux, and in future, probably also the new oral anticoagulants dabigatran and rivaroxaban) may conflict with regional anesthetic techniques, in which maintaining hemostatic integrity is essential. Therefore, safety protocols have been designed that allow thromboprophylaxis to be administered with optimal effectiveness and anesthetic techniques to be performed with maximal safety; these protocols are based on the drug used, as well as on the dose and time of administration. The present chapter reviews the details related to these issues.

Topics: Acenocoumarol; Administration, Oral; Anesthesia, Conduction; Anticoagulants; Benzimidazoles; Clinical Protocols; Dabigatran; Early Ambulation; Fibrinolytic Agents; Fondaparinux; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Risk Factors; Rivaroxaban; Safety; Surgical Procedures, Operative; Thiophenes; Venous Thromboembolism; Venous Thrombosis

Rivaroxaban (Xarelto) is a new oral, direct and selective inhibitor of the factor Xa of the coagulation cascade. The main pharmacokinetic characteristics of rivaroxaban are a bioavailability of approximately 80-100%, a maximum concentration obtained in 2 to 4 hours, a terminal half-life of elimination of 7 to 11 hours, a renal elimination for 1/3 for the active hepatic metabolism from the cytochrome P450 (3A4) for the other 2/3. The main sources of variability are the renal and the liver function and potential interactions with some strong inhibitors or inducers of the CYP450 3A4. Phase II clinical studies have shown that this compound can be orally administrated, once or twice daily, without any biological monitoring and without any need for dose adjustment. There is a contra-indication in case of severe liver insufficiency and not recommended in case of severe renal impairment. Pharmacodynamically, Rivaroxaban is a direct and selective factor Xa inhibitor without any effect on the factor IIa and without any interaction on platelets. Four phases II with 2787 patients were carried out to for venous thromboembolic (VTE) prophylaxis after major orthopaedic surgery, showing that 10 mg once daily could be the optimal dose regimen to assess in phase III. Two phases II with 1446 patients were carried out for the treatment of VTE showing that 15 mg twice daily for 3 weeks and then 20 mg once daily could be the optimal dose regimen to evaluate in the following phases 3. No strong signal for a potential liver toxicity was shown during these 6 phases II.

Topics: Administration, Oral; Aged; Anticoagulants; Biological Availability; Clinical Trials as Topic; Contraindications; Cytochrome P-450 CYP3A; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Metabolic Clearance Rate; Middle Aged; Molecular Structure; Morpholines; Orthopedic Procedures; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Venous Thrombosis

The overall thromboembolic risk is the resultant of patient-related risk and surgical risk. The surgical risk is decreasing, especially with the introduction of new procedures (fast-track surgery). The value of prophylaxis has been firmly established. Mechanical prophylaxis is to be used as first-line prophylaxis when there is a risk of bleeding. Combining this with drugs increases the antithrombotic efficacy. However, the effectiveness of prophylaxis on pulmonary embolism and mortality has not been demonstrated. Renal function needs to be evaluated when low molecular weight heparins, fondaparinux, rivaroxaban or dabigatran are prescribed. An age of over 75 years and low body weight (<50 kg) have to be taken into account. There is a risk of spinal or epidural hematoma in patients receiving anticoagulants. Caution should be taken especially when administering the newer agents. Patients undergoing surgery that involves a moderate or high overall risk should receive prophylaxis until full mobilization. Patients who have undergone a total hip replacement, surgery for hip fracture, or major abdominal surgery should receive prophylaxis for about 5 weeks longer. The relevance of distal vein thromboses is debated. Surrogate venographic end-points should be gradually replaced by a combination of ultrasound and clinical criteria. The new antithrombotic agents will probably modify prevention in the years to come but currently there are very few long-term data for these products for which - it should be reminded - no antagonists are available.

Topics: Adult; Aged; Anticoagulants; Combined Modality Therapy; Fibrinolytic Agents; Fondaparinux; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Middle Aged; Morpholines; Polysaccharides; Postoperative Complications; Preanesthetic Medication; Pulmonary Embolism; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Thromboembolism; Thrombophlebitis; Vitamin K

The oral direct Xa inhibitor rivaroxaban (Xarelto) shows great promise for prevention of venous thromboembolic events after major elective orthopedic surgery. Its consistent and predictable pharmacokinetics and pharmacodynamics across a wide range of patient populations allow administration with fixed dosing and with no coagulation monitoring. In 4 orthopaedic surgery clinical trials (12,700 patients), 10mg postoperative (6-10 hours after the end of surgery) dose, once daily, of oral rivaroxaban, achieved superior efficacy and similar safety to enoxaparin, whatever the dose of enoxaparin. Indeed, 40 mg once a day in Europe and 30 mg bid in US of enoxaparin were compared to the same dose of 10mg once daily of rivaroxaban. Furthermore, there is no difference according to liver enzymes elevation and cardio-vascular adverse events. Although the risk of spinal haematoma after neuraxial anaesthesia is rare, it is increased by concomitant use of anticoagulants. In orthopedic surgery trials with rivaroxaban to date, complications such as spinal haematoma have not been reported. The pharmacokinetic profile of rivaroxaban suggests that concurrent use with neuraxial anaesthesia should require no further precautions than currently necessary with low-molecular-weight heparin.

Topics: Administration, Oral; Anticoagulants; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hematoma, Epidural, Spinal; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Morpholines; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Thromboembolism

Rivaroxaban is the first oral anticoagulant with a direct anti-Xa activity to be registered (approval). As for all first comers in a class, it should be assessed both for itself and for the class. The targeting of factor-Xa factor, key component in the coagulation cascade, has the theoretical benefit of being an effective antithrombotic and a potential risk for hemorrhage, both highly dose-dependent. Experience has shown us that the representativeness and predictiveness of in vitro tests and preclinical models are only partial and sometimes even misleading. This is why the responses can only come from clinical trials and rigorous research testing doses, which should be conducted specifically in all the indications foreseen, with no extrapolations. The oral anticoagulant drugs are developed in the prevention of arterial thromboembolic events caused by atrial fibrillation too, where the vitamin K antagonists (VKAs) are the current standard of care. The well-known problems of monitoring and adaptation doses with VKAs have led to developing new replacement classes without the need for control or biological adaptation. However, in certain conditions there is a need to monitor the patient. The advantage for the direct anti-Xa inhibitors such as rivaroxaban is that the prothrombin time, a routine test is sensitive and provides a prolonged response that is proportional to the plasma concentration within a wide range of concentrations. This test is potentially usable provided that the indispensable standardization is forthcoming.

Topics: Administration, Oral; Anticoagulants; Clinical Trials as Topic; Drug Administration Schedule; Drug Monitoring; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; Molecular Structure; Morpholines; Postoperative Complications; Preanesthetic Medication; Prothrombin Time; Rivaroxaban; Thiophenes; Thrombin; Thromboembolism; Vitamin K; Warfarin

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.

Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Aged, 80 and over; Animals; Anticoagulants; Atrial Fibrillation; Binding Sites; Clinical Trials as Topic; Comorbidity; Drug Evaluation, Preclinical; Factor Xa; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Rats; Rivaroxaban; Stroke; Thiophenes; Thrombosis; Warfarin

Bayer AG and Ortho-McNeil Pharmaceutical Inc are developing rivaroxaban, an oral Factor Xa inhibitor, for the potential prevention and treatment of thrombosis. In December 2005 and December 2006, phase III trials were initiated for the prevention of venous thromboembolism (VTE) following major orthopedic surgery and in patients with atrial fibrillation, respectively. By January 2007, a phase III trial for the prevention of VTE following total knee replacement surgery had commenced. In November 2006, a phase II trial for the reduction of VTE in patients with acute coronary syndrome was initiated.

Topics: Administration, Oral; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Humans; Molecular Structure; Morpholines; Patents as Topic; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Thromboembolism

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking.. To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery.. This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland.. Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis).. The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality.. Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm.. In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups.. ClinicalTrials.gov Identifier: NCT03522259.

Topics: Adult; Anticoagulants; Female; Hemorrhage; Humans; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism

BACKGROUND Venous thrombosis (VTE) is a common adverse event among inpatients, which can cause pulmonary embolism, and greatly increases mortality. The effects of rivaroxaban in patients undergoing brain glioma surgery have still not been explored. This single-center study of 94 patients undergoing surgery for cerebral glioma aimed to compare postoperative thromboprophylaxis with and without rivaroxaban. MATERIAL AND METHODS We designed a randomized, controlled, double-blind study to evaluate the effect of rivaroxaban on 94 patients undergoing brain glioma surgery. These patients were divided into a rivaroxaban group (administered at 10 mg per day from admission to discharge) and a placebo group. The primary study endpoint was incidence of VTE at discharge. The secondary endpoints included safety outcomes of major bleeding, allergy, or VTE-related death. RESULTS A total of 94 patients were enrolled in the study: 47 in the rivaroxaban group and 47 in the placebo group. Baseline characteristics of participants were well-matched in both groups. A significant reduction was found in the incidence of VTE in the rivaroxaban treatment group versus the placebo group (1/47 vs 10/47 patients, P=0.008). The rate of major bleeding events was quite low in both group (1/47 vs 1/47 patients). One patient in the placebo group died due to a pulmonary embolism and intractable concomitant underlying diseases. CONCLUSIONS Our results indicate that treatment with rivaroxaban is a safe and effective thromboprophylaxis treatment in patients undergoing surgery for malignant cerebral glioma.

Topics: Brain Neoplasms; Double-Blind Method; Factor Xa Inhibitors; Glioma; Humans; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Topics: Administration, Oral; Antithrombins; Arthroplasty; Dabigatran; Humans; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Venous Thrombosis

For the non-vitamin-K oral anticoagulants, data on bleeding when used for 42 days as thromboprophylaxis after total knee arthroplasty (TKA) are scarce. This pilot study assessed feasibility of a multicentre randomised clinical trial to evaluate major and clinically relevant non-major bleeding during 42-day use of dabigatran, nadroparin and rivaroxaban after TKA.. In 70 weeks, between July 2012 and November 2013, 198 TKA patients were screened for eligibility in the Martini Hospital (Groningen, the Netherlands). Patients were randomly assigned to dabigatran (n=45), nadroparin (n=45) or rivaroxaban (n=48). The primary outcome was the combined endpoint of major bleeding and clinically relevant non-major bleeding. Secondary endpoints of this study were the occurrence of clinical venous thromboembolism (VTE) (pulmonary embolism or deep venous thrombosis), compliance, duration of hospital stay, rehospitalisation, adverse events and Knee Injury and Osteoarthritis Outcome Score (KOOS).. The primary outcome was observed in 33.3% (95% CI 20.0% to 49.0%), 24.4% (95% CI 12.9% to 39.5%) and 27.1% (95% CI 15.3% to 41.8%) of patients who received dabigatran, nadroparin or rivaroxaban, respectively (p=0.67). Major bleeding was found in two patients who received nadroparin (p=0.21). Clinically relevant non-major bleeding was observed in 33.3% (95% CI 20.0% to 49.0%), 22.2% (95% CI 11.2% to 37.1%) and 27.1% (95% CI 15.3% to 41.8%) for dabigatran, nadroparin and rivaroxaban, respectively (p=0.51). Wound haematoma was the most observed bleeding event. VTE was found in one patient who received dabigatran (p=0.65). The presurgery and postsurgery KOOS qQuestionnaires were available for 32 (71%), 35 (77%) and 35 (73%) patients for dabigatran, nadroparin and rivaroxaban, respectively. KOOS was highly variable, and no significant difference between treatment groups in mean improvement was observed.. A multicentre clinical trial may be feasible. However, investments will be substantial. No differences in major and clinically relevant non-major bleeding events were found between dabigatran, nadroparin and rivaroxaban during 42 days after TKA. KOOS may not be suitable to detect functional loss due to bleeding.. NCT01431456.

Topics: Activities of Daily Living; Anticoagulants; Arthroplasty, Replacement, Knee; Dabigatran; Female; Humans; Nadroparin; Netherlands; Pilot Projects; Postoperative Care; Postoperative Complications; Quality of Life; Rivaroxaban; Treatment Outcome; Venous Thromboembolism

Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.. In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.. A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P<0.001 for noninferiority; P = 0.01 for superiority). The incidence of bleeding did not differ significantly between the rivaroxaban group and the enoxaparin group (1.1% and 1.0%, respectively, for major bleeding or nonmajor clinically relevant bleeding; 0.6% and 0.7%, respectively, for major bleeding).. Rivaroxaban was more effective than enoxaparin in the prevention of venous thromboembolic events during a period of immobilization after nonmajor orthopedic surgery of the lower limbs. (Funded by Centre Hospitalier Universitaire de Saint-Etienne and Bayer; PRONOMOS ClinicalTrials.gov number, NCT02401594.).

Topics: Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Enoxaparin; Female; Hemorrhage; Humans; Injections, Subcutaneous; Lower Extremity; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism; Venous Thrombosis

Anticoagulant plasma concentrations and patient characteristics might affect the benefit-risk balance of therapy. The study objective was to assess the impact of model-predicted rivaroxaban exposure and patient characteristics on outcomes in patients receiving rivaroxaban for venous thromboembolism (VTE) prophylaxis (VTE-P) after hip/knee replacement surgery. Post hoc exposure-response analyses were conducted using data from the phase 3 RECORD1-4 studies, in which 12,729 patients were randomized to rivaroxaban 10 mg once daily or enoxaparin for ≤ 39 days. Multivariate regression approaches were used to correlate model-predicted individual rivaroxaban exposures and patient characteristics with outcomes. In the absence of measured rivaroxaban exposure, exposure estimates were predicted based on individual increases in prothrombin time (PT) and by making use of the known correlation between rivaroxaban plasma concentration and dynamics of PT. No significant associations between rivaroxaban exposure and total VTE or major bleeding were identified. A significant association between exposure and a composite of major or non-major clinically relevant (NMCR) bleeding from day 4 after surgery was observed. The relationship was shallow, with an approximate predicted absolute increase in a composite of major or NMCR bleeding from 1.08 [95% confidence interval (CI) 0.76-1.54] to 2.18% (95% CI 1.51-3.17) at the 5th and 95th percentiles of trough plasma concentration, respectively. In conclusion, based on the underlying data and analysis, no reliable target window for exposure with improved benefit-risk could be identified within the investigated exposure range. Hence, monitoring rivaroxaban levels is unlikely to be beneficial in VTE-P.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Biomarkers, Pharmacological; Chemoprevention; Drug Monitoring; Female; Hemorrhage; Humans; Male; Middle Aged; Models, Statistical; Postoperative Complications; Prognosis; Prothrombin Time; Risk Adjustment; Risk Assessment; Rivaroxaban; Venous Thromboembolism

Data on the comparison between uninterrupted and interrupted by one dose strategies for direct oral anticoagulant (DOAC) use during the periprocedural period of atrial fibrillation (AF) ablation are scarce. The purpose of this study is to investigate the feasibility of uninterrupted DOAC strategy by evaluating the incidence of silent stroke (SS) and perioperative trends in coagulation markers compared with the interrupted strategy.. We randomly divided 200 consecutive patients receiving DOACs, who underwent AF ablation into uninterrupted group (UG = 100) and interrupted by one dose group (IG = 100). The rate of SS confirmed by post-operative magnetic resonance imaging and periprocedural trends in coagulation markers was investigated. A significant difference in SS incidence was found between the UG and IG (UG 4%, IG 17%, P < 0.005), although there were no differences in the rate of complications including bleeding and symptomatic thrombo-embolic events between the two groups. Intraoperative cardioversion [odds ratio (OR) 7.27, 95% confidence interval (CI) 1.76-30.0; P < 0.01] and the length of procedure time (OR 1.03, 95% CI 1.01-1.05; P < 0.05) independently predicted the occurrence of SS in the IG. A significant increase in prothrombin fragment 1 + 2 (PF1 + 2) values was observed in the IG compared with the UG on the operative and first post-operative days.. Silent stroke incidence in the IG was significantly higher than that in the UG; this seems to be supported by the difference in PF1 + 2 values between the UG and IG. Intraoperative cardioversion and procedure time predicted the occurrence of SS in the IG.

Topics: Adult; Aged; Aged, 80 and over; Asymptomatic Diseases; Atrial Fibrillation; Catheter Ablation; Factor Xa Inhibitors; Female; Humans; Incidence; Magnetic Resonance Imaging; Male; Middle Aged; Peptide Fragments; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Prothrombin; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles

The Fontan procedure is the final step of the 3-stage palliative procedure commonly performed in children with single ventricle physiology. Thrombosis remains an important complication in children after this procedure. To date, guideline recommendations for the type and duration of thromboprophylaxis after Fontan surgery are mainly based on extrapolation of knowledge gained from adults at risk for thrombosis in other clinical settings. Warfarin is being used off-label, and because of its multiple interactions with other drugs and food, a new alternative is highly desirable. Rivaroxaban, a direct Factor Xa inhibitor with a predictable pharmacokinetic profile, is a candidate to address this medical need.. The UNIVERSE study is a prospective, open-label, active-controlled, multicenter study in children 2 to 8 years of age who have single ventricle physiology and had the Fontan procedure within the 4 months preceding enrollment. This study consists of 2 parts. In Part A, rivaroxaban pharmacokinetics, pharmacodynamics, safety, and tolerability are assessed to validate the pediatric dosing selected. In Part B, safety and efficacy of rivaroxaban versus acetylsalicylic acid are evaluated for thromboprophylaxis in children post-Fontan procedure. Children in each part will receive study drug for 12 months. Part A has been completed with 12 children enrolled. Enrollment into Part B is currently ongoing.. The UNIVERSE study aims to provide dosing, pharmacokinetics/pharmacodynamics, safety, and efficacy information on the use of rivaroxaban, an oral anticoagulant, versus acetylsalicylic acid, an antiplatelet agent, in children with single ventricle physiology after the Fontan procedure.

Topics: Aspirin; Child; Child, Preschool; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fontan Procedure; Humans; Male; Multicenter Studies as Topic; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; Rivaroxaban; Thrombosis

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge.. We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome).. A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43).. Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Double-Blind Method; Factor Xa Inhibitors; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Risk Factors; Rivaroxaban; Venous Thromboembolism

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Double-Blind Method; Equivalence Trials as Topic; Female; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Most international guidelines recommend pharmacological thromboprophylaxis after total hip and knee arthroplasty (THA/TKA) for 10 to 35 days. However, a recent cohort study on fast-track THA and TKA questioned the need for prolonged thromboprophylaxis when length of stay (LOS) is ≤ 5 days. We aimed at re-investigating the incidence of venous thromboembolism (VTE) in fast-track THA and TKA with in-hospital only thromboprophylaxis when LOS was ≤ 5 days. Prospective cohort study from 1 December 2011 to 30 October 2015 on elective unilateral THA/TKA with in-hospital only thromboprophylaxis if LOS was ≤ 5 days. Prospective information on co-morbidity and complete 90-day follow-up through the Danish National Patient Registry and medical records. Patients with pre-operative use of anticoagulants were excluded. In per protocol analysis, 17,582 (95.5%) had LOS of ≤ 5 days (median, 2 [interquartile range, 2-3]) and in-hospital thromboprophylaxis only. Incidence of symptomatic VTE was 0.40%, consisting of 28 (0.16%) pulmonary embolisms (PEs), 38 (0.22%) deep vein thrombosis (DVT) and 4 (0.02%) combined DVT and PE. Two PEs (0.01%) were fatal. VTE-associated risk factors with in-hospital only thromboprophylaxis were age > 85 years, odds ratio (OR) of 3.74 (95% confidence interval: 1.15-12.14,

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dalteparin; Denmark; Enoxaparin; Follow-Up Studies; Hospitals; Humans; Incidence; Middle Aged; Postoperative Complications; Prospective Studies; Risk; Rivaroxaban; Survival Analysis; Venous Thromboembolism

Guidelines recommend warfarin continuation rather than heparin bridging for pacemaker and defibrillator surgery, after the BRUISE CONTROL trial demonstrated an 80% reduction in device pocket haematoma with this approach. However, direct oral anticoagulants (DOACs) are now used to treat the majority of patients with atrial fibrillation. We sought to understand the best strategy to manage the DOACs at the time of device surgery and specifically hypothesized that performing device surgery without DOAC interruption would result in a reduced haematoma rate.. We randomly assigned patients with atrial fibrillation and CHA2DS2-VASc score ≥2, to continued vs. interrupted DOAC (dabigatran, rivaroxaban, or apixaban). The primary outcome was blindly evaluated, clinically significant device pocket haematoma: resulting in re-operation, interruption of anticoagulation, or prolonging hospital stay. In the continued arm, the median time between pre- and post-operative DOAC doses was 12 h; in the interrupted arm the median time was 72 h. Clinically significant haematoma occurred in of 7 of 328 (2.1%; 95% CI 0.9-4.3) patients in the continued DOAC arm and 7 of 334 (2.1%; 95% CI 0.9-4.3) patients in the interrupted DOAC arm (P = 0.97). Complications were uncommon, and included one stroke and one symptomatic pericardial effusion in each arm.. These results suggest that, dependent on the clinical scenario, either management strategy (continued DOAC or interrupted DOAC) might be reasonable, at least for patients similar to those enrolled in our trial.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cardiac Pacing, Artificial; Dabigatran; Defibrillators, Implantable; Drug Administration Schedule; Female; Hematoma; Humans; Length of Stay; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Reoperation; Rivaroxaban; Thromboembolism

The effectiveness of preoperative thromboprophylaxis remains obscure in patients with femoral neck fracture. The purpose of the current study was to investigate whether these patients benefit from preoperative thromboprophylaxis.. In this prospective, randomized controlled trial, a total of 80 patients with femoral neck fracture were randomly assigned to receive either rivaroxaban or conservative treatment before surgery. For all patients, color Doppler ultrasound of both lower extremities was performed immediately after admission. The primary efficacy outcome was venous thromboembolism (VTE) defined as deep vein thrombosis (DVT) or pulmonary embolism (PE). The primary safety outcome was major bleeding.. Compared with conservative treatment, rivaroxaban could significantly reduce the incidence of DVT from 19.5% (8/41) to 2.6% (1/39) (P = .016). Preoperatively, there were a total of 9 occurrences of DVT including 8 DVT in the conservative treatment group and 1 in the oral rivaroxaban group. All cases of DVT were asymptomatic, with 8 of them diagnosed as isolated muscular calf vein thromboses. There were no differences between the 2 groups in terms of the overall incidence of major bleeding.. Thromboprophylaxis with rivaroxaban prior to surgery can effectively reduce the risk of preoperative DVT for patients with femoral neck fracture without increasing the risk of bleeding.

Topics: Administration, Oral; Aged; Aged, 80 and over; Conservative Treatment; Factor Xa Inhibitors; Female; Femoral Neck Fractures; Hemorrhage; Humans; Incidence; Male; Middle Aged; Postoperative Complications; Preoperative Care; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thrombosis

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol.\ \ Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group.\ \ Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Topics: Administration, Oral; Adult; Anticoagulants; Atrial Fibrillation; Canada; Cardiac Surgical Procedures; Cohort Studies; Dabigatran; Female; Hemorrhage; Humans; Male; Perioperative Period; Postoperative Complications; Precision Medicine; Prospective Studies; Pyrazoles; Pyridones; Rivaroxaban

Topics: Adult; Anticoagulants; Brain Injuries, Traumatic; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Treatment Outcome; Venous Thrombosis

In global admission studies (RECORD I-IV) Rivaroxaban and enoxaparin as a standard prophylaxis were comparable in safety of treatment, but rivaroxaban appeared more effective in prevention of venous thromboembolism (VTE) when used in elective hip and knee replacement. The worldwide non-interventional cohort study XAMOS confirmed these results in the clinical routine compared to proven anticoagulants.. Efficacy and safety of rivaroxaban was to be compared with the standard prophylaxis in the prevention of VTE after elective hip and knee replacement surgery in clinical practice in Germany. For this purpose a subanalysis of the 2,719 patients (XAMOS-DE) included in XAMOS in German study centers was performed.. Out of 2,719 patients in 32 study centers 1,333 patients obtained rivaroxaban and 1,386 patients obtained standard prophylaxis. The incidence of symptomatic VTE-events (0.9% with rivaroxaban vs. 1.1% with standard prophylaxis) and severe bleeding by RECORD (0.5% vs. 0.9%) and EMA criteria (2.9 % vs. 3.0%) was similar in both groups. Most of the patients treated with rivaroxaban rated tolerability as "very good" and therapy as "very patient-friendly".. The results from XAMOS-DE confirm in clinical practice the favorable benefit-risk ratio of rivaroxaban, as well as the current S3 guidelines for thromboembolism prophylaxis with rivaroxaban in elective hip and knee replacement.

Topics: Aged; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Female; Germany; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Thrombosis

Patients on rivaroxaban have variable international normalized ratios (INRs) but it is uncertain if INR impacts procedural heparin requirement during left atrial ablation. We sought to examine the determinants of heparin dosing in this patient population.. We reviewed consecutive patients who received rivaroxaban within 24 hours of left atrial ablation and compared them to patients on uninterrupted warfarin. The determinants of heparin requirement were evaluated using regression analysis. We then tested a weight-based heparin dose prospectively in rivaroxaban patients.. There were 258 patients on rivaroxaban and 213 on warfarin. The mean INR was 1.4 in the rivaroxaban group and 2.3 in the warfarin group (P < 0.01). To achieve an activated clotting time (ACT) >350 seconds, rivaroxaban patients required significantly more heparin (166.9 vs. 78.3 units/kg, P < 0.001). In the rivaroxaban group, body weight was the strongest predictor of heparin dose (r = 0.52), while INR was weakly correlated (r = -0.21). In the prospective group, 25 patients were given an initial heparin dose of 120 units/kg with 22/25 (88%) achieving an ACT > 300 seconds. There were seven and three cases of pericardial effusion in rivaroxaban and warfarin patients, respectively (P = 0.41). The average volume drained in the rivaroxaban group was elevated (988.6 vs. 275.0 mL, P = 0.21).. Body weight is the strongest predictor of procedural heparin requirement during left atrial ablation in patients on uninterrupted rivaroxaban, even in those with an elevated INR. A heparin dose of 120 units/kg achieves an ACT > 300 seconds in the majority of patients. In cases of pericardial effusion, bleeding may be prolonged.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Body Weight; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heart Atria; Heparin; Humans; Male; Middle Aged; Postoperative Complications; Premedication; Prevalence; Risk Factors; Rivaroxaban; Thromboembolism; Treatment Outcome; United States

Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients.. In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion.. Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 μg·h l. Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.

Topics: Administration, Oral; Adult; Antithrombins; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Gastric Bypass; Half-Life; Humans; Male; Middle Aged; Obesity; Postoperative Complications; Postoperative Period; Preoperative Period; Prothrombin; Rivaroxaban; Thrombin; Venous Thromboembolism

BACKGROUND This study aimed to assess whether the efficacy of tranexamic acid (TXA) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement (TKR). It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin. MATERIAL AND METHODS A randomized clinical trial was conducted on 194 patients undergoing primary TKR for osteoarthritis. An intravenous dose of 15 mg/kg (TXA) and 1 g topical TXA were used. Patients randomly received enoxaparin or rivaroxaban prophylaxis when the drainage was less than 30 ml/h 6-8 h postoperatively. The primary endpoint was hidden blood loss (HBL). Indexes of total blood loss drainage, hemoglobin drop, transfusion, range of motion (ROM), HSS score, VAS pain score, knee swelling, length of hospital stay (LOHS), incidence of venous thromboembolism, major/minor bleeding, and wound complications were also compared between the groups. RESULTS More than 80% of patients initiated anticoagulation within 6 h postoperatively. No statistically significance difference was detected in terms of HBL (679.0±205.6 vs. 770.5±206.1, p=.062) or other bleeding index, ROM, or LOHS. The motion VAS pain score and knee swelling (16.7% vs. 6.1%, p=.021) were significantly lower, and HSS score at discharge was higher in the enoxaparin group. The rivaroxaban group had less asymptomatic deep venous (4.1% vs. 0%, p=.121) and muscular venous thrombosis (2.1% vs. 9.2%, p=.033); more ecchymosis (13.5% vs. 10.2%, p=.472), and wound complications (13.5% vs. 6.1%, p=.082). No episodes of transfusion, pulmonary embolism, or major bleeding occurred in either group. CONCLUSIONS More attention should be paid to the increased risk of wound complications and knee swelling associated with rivaroxaban, although the hidden blood loss was similar in both groups.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Coagulation; Drug Interactions; Enoxaparin; Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Osteoarthritis; Pilot Projects; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Tranexamic Acid; Venous Thromboembolism

The risk of venous thromboembolism is high in patients undergoing fracture-related major orthopedic surgery, but data on pharmacological thromboprophylaxis are limited. This analysis evaluated the effectiveness and safety of rivaroxaban after fracture-related orthopedic surgery in routine care compared with other pharmacological thromboprophylaxis (standard of care [SOC]).. The study population comprised a subset of patients with lower-limb fracture from XArelto in the prophylaxis of post-surgical venous thromboembolism after elective Major Orthopaedic Surgery of hip or knee (XAMOS; a phase IV noninterventional study) and a XAMOS extension study (XAMOS-Extra). The study participants included patients who underwent surgery for hip/femur or lower-leg fractures (below-knee lower-leg fractures, eg, the tibia or foot). All adverse events were recorded, including symptomatic thromboembolic events and bleeding events.. Data from 790 patients were available for analysis (n = 350 for rivaroxaban and n = 440 for SOC). The incidence of symptomatic thromboembolic events 3 months postsurgery was 0.57% (2 of the 350) in the rivaroxaban group and 1.14% (5 of the 440) in the SOC group (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.10-2.59). Treatment-emergent major bleeding events occurred in 0.29% (1 of the 350) of patients receiving rivaroxaban and 0.45% (2 of the 440) of patients receiving SOC (OR: 0.63; 95% CI: 0.06-6.95). There were no cases of fatal or critical bleeding in either treatment group. The incidences of wound complications and any other adverse events were numerically lower with rivaroxaban compared with SOC.. These data from routine practice demonstrate that rivaroxaban can provide effective thromboprophylaxis after fracture-related orthopedic surgery of the lower limb with a favorable safety profile.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Fractures, Bone; Humans; Incidence; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thromboembolism

This prospective study was conducted to report the effect of oral factor Xa inhibitor and low-molecular-weight heparin (LMWH) on surgical complications following total hip arthroplasty (THA). The patients with an age < 60 years were randomly assigned to three groups (rivaroxaban, enoxaparin, and placebo) and the patients with an age ≥ 60 years were assigned to two groups (rivaroxaban and enoxaparin). All drug regimens started at 12 hours postoperatively and continued for two weeks after surgery. Primary measure outcome was major surgical wound complications defined as haematoma requiring any intervention, superficial wound infection, deep periprosthetic infection, and increased wound bleeding. Secondary measured outcome included minor surgical complications (swelling, drainage, erythema, and oozing), organ bleeding, and venous thromboembolic (VTE) events. A total of 184 patients aged < 60 years and 167 patients aged ≥ 60 years were included as the analysis population per group. Up to 14 days after surgery, the overall incidence of major surgical complications associated with thromboprophylaxis was 6.5 % (58/886). There were no significant differences in the rate of major surgical complications among all the three groups of the patients aged < 60 years and between two groups of the patients aged ≥ 60 years. For the patients aged < 60 years, wound oozing continued significantly longer in the pharmacological group than in the placebo group, but wound infection did not occur in any case. The VTE events were similar in all the groups.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Placebos; Postoperative Complications; Postoperative Period; Prospective Studies; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Wound Healing

Patients on rivaroxaban requiring percutaneous coronary intervention (PCI) represent a clinical conundrum. We aimed to investigate whether rivaroxaban, with or without an additional bolus of unfractionated heparin (UFH), effectively inhibits coagulation activation during PCI. Stable patients (n=108) undergoing elective PCI and on stable dual antiplatelet therapy were randomised (2:2:2:1) to a short treatment course of rivaroxaban 10 mg (n=30), rivaroxaban 20 mg (n=32), rivaroxaban 10 mg plus UFH (n=30) or standard peri-procedural UFH (n=16). Blood samples for markers of thrombin generation and coagulation activation were drawn prior to and at 0, 0.5, 2, 6-8 and 48 hours (h) after start of PCI. In patients treated with rivaroxaban (10 or 20 mg) and patients treated with rivaroxaban plus heparin, the levels of prothrombin fragment 1 + 2 at 2 h post-PCI were 0.16 [0.1] nmol/l (median) [interquartile range, IQR] and 0.17 [0.2] nmol/l, respectively. Thrombin-antithrombin complex values at 2 h post-PCI were 3.90 [6.8]µg/l and 3.90 [10.1] µg/l, respectively, remaining below the upper reference limit (URL) after PCI and stenting. This was comparable to the control group of UFH treatment alone. However, median values for thrombin-antithrombin complex passed above the URL with increasing tendency, starting at 2 h post-PCI in the UFH-alone arm but not in rivaroxaban-treated patients. In this exploratory trial, rivaroxaban effectively suppressed coagulation activation after elective PCI and stenting.

Topics: Aged; Anticoagulants; Antithrombin III; Biomarkers; Coronary Disease; Drug Therapy, Combination; Elective Surgical Procedures; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Heparin; Humans; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Complications; Prothrombin; Risk Factors; Rivaroxaban; Single-Blind Method; Stents; Thrombin; Thrombosis

Prevention of deep venous thrombosis (DVT) and associated pulmonary embolism following major orthopedic surgeries is challenging, and there is an increased interest in developing new treatment strategies. We compared 2 switch-therapy modalities-enoxaparin to rivaroxaban and enoxaparin to dabigatran-and enoxaparin monotherapy for preventing DVT after total knee arthroplasty (TKA) and total hip arthroplasty (THA).. This was a prospective, non-blinded, randomized controlled study. We selected 180 eligible patients out of 247 patients undergoing TKA or THA. During the preoperative checkup, patients were randomized to receive either enoxaparin (enoxaparin group) or switch-therapy regimens, comprising enoxaparin during hospitalization and rivaroxaban (rivaroxaban group) or dabigatran (dabigatran group) during the outpatient period. All patients were evaluated for DVT using Doppler ultrasonography (USG) 6 weeks postoperatively. The primary efficacy outcome was the prevention of symptomatic or Doppler ultrasonography (USG)-proven DVT, whereas the primary safety outcome was the incidence of bleeding during the DVT-prophylaxis period.. Doppler USG at 6 weeks after surgery revealed no signs of DVT in any patient. During the hospitalization period, only 2 major bleeding events were reported (1 [1.6%] in the enoxaparin group and 1 [1.6%] in the dabigatran group). No major bleeding events were reported during the outpatient follow-up period in any group. Differences among the 3 groups regarding bleeding events were not statistically significant (p>0.05).. When using switch-therapy modalities, clinicians can take advantage of the safety of enoxaparin during the hospitalization period and ease of use of new oral anticoagulant drugs during the outpatient period.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Rivaroxaban; Ultrasonography, Doppler; Venous Thrombosis

Thromboprophylaxis with rivaroxaban has proved effective and safe in patients undergoing hip and knee replacement surgery. As it is unclear whether it is also effective and safe in fracture patients, the aim of the present study was to evaluate the efficacy and safety of rivaroxaban in patients with lower limb fractures. We performed a retrospective cohort study of 2,050 consecutive patients treated for lower limb fractures at our trauma center, comparing rates of venous thromboembolism (VTE), bleeding and surgical complications, and the length of hospital stay for 608 patients who received rivaroxaban and 717 who received a low-molecular-weight heparin (LMWH). Rates of symptomatic VTE were 4.9 and 8.6% in the rivaroxaban and LMWH groups, respectively (p = 0.008), and distal VTE rates were 1.8 and 5.7%, respectively (p = 0.036). The incidence of major bleeding events in the rivaroxaban group was also lower than in the LMWH group (0.2 vs 0.6%), but the difference between the groups was not statistically significant. The mean length of hospital stay was significantly shorter in the rivaroxaban group (12.2 vs 13.1 days, respectively; p = 0.016). This retrospective cohort study is the first report documenting the efficacy and safety of rivaroxaban in patients with lower extremity fractures. In comparison with LMWH, rivaroxaban reduced the incidence of VTE by 45% without increasing the risk of bleeding. However, prospective, randomized controlled trials comparing rivaroxaban and LMWH are needed to confirm our findings.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Factor Xa Inhibitors; Female; Fractures, Bone; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Length of Stay; Lower Extremity; Male; Middle Aged; Morpholines; Postoperative Complications; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism

To investigate the risk of hidden blood loss about applying rivaroxaban after total hip arthroplasty.. From October 2009 to May 2012,88 patients with femoral head necrosis were treated with primary total hip arthroplasty. All the patients were divided into Rivaroxaban group(44 cases)and control group(44 cases). There were 25 males and 19 females in the Rivaroxaban group, with an average age of (58.48 +/- 15.19) years old; in the control group,24 patients were male and 20 patients were female, with an average age of (61.11 +/- 13.54) years old. The patients in the Rivaroxaban group took Rivaroxaban orally from the first day after operation with a dose of 10 mg each day, and treatment course was 14 days. The patients in the control group took placebo orally at the same time. Dominant blood loss and transfusion were recorded, blood routine examinations were taken before operation and at 3 days after operation. The total blood loss and hidden blood loss were calculated according to the formula.. The mean total blood loss was (1509.56 +/- 325.23) ml and the hidden blood loss was(581.47 +/- 215.01) ml, accounting for (37.88 +/- 10.42)% in the Rivaroxaban group. The mean total blood loss was (1262.30 +/- 397.95) ml and the hidden blood loss was (395.59 +/- 97.33) ml, accounting for (30.62 +/- 0.20)% in the control group. The total blood loss, hidden blood loss and transfusion in the Rivaroxaban group was significantly more than those in control group,b ut there was no significant difference on dominant blood loss between two groups.. Rivaroxaban increased the overall bleeding risk of total hip arthroplasty, especially hidden bleeding risk, which should be careful used.

Topics: Arthroplasty, Replacement, Hip; Case-Control Studies; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Risk; Rivaroxaban; Thiophenes; Time Factors

TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2-4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9-9.6), 5.2% (95%CI 2.8-9.3) and 4.7% (95%CI 2.5-8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3-9.9), 7.2% (95%CI 4.4-11.6) and 1.4% (95%CI 0.5-4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Patient Safety; Postoperative Complications; Risk; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

Venous thromboembolism (VTE) has a significant impact on healthcare costs but is largely preventable with anticoagulant prophylaxis using low-molecular-weight heparins (LMWHs), such as enoxaparin or dalteparin. Rivaroxaban and dabigatran etexilate are two new oral anticoagulants (NOACs) both compared with enoxaparin in separate trials. A decision analytic model with a healthcare and national payer perspective over a five-year time horizon was used to evaluate the cost-effectiveness of the NOACs for VTE prophylaxis after total hip replacement (THR) or total knee replacement (TKR) in France, Italy and Spain. Efficacy and safety data were obtained from randomised controlled trials of rivaroxaban vs enoxaparin and an indirect statistical comparison for rivaroxaban vs dabigatran. Rivaroxaban demonstrated dominance across all comparisons, indications and countries. In THR, total per-patient costs were reduced by up to €160 in the enoxaparin comparison and €115 in the dabigatran comparison, respectively. In addition, quality-adjusted life-years (QALYs) were increased by up to 0.0011 and 0.0012 in each comparison, respectively. Similarly, total costs were reduced in TKR by up to €137 and €28 in the enoxaparin and dabigatran comparisons, respectively. The total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison and 0.0005 in the dabigatran comparison. The results were driven by costs since the incremental benefits were minimal. Rivaroxaban use could result in substantial healthcare cost savings and improved quality of life. The results are applicable across three European countries with differing healthcare systems so, potentially, could be generalised to a much wider population.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Cost of Illness; Cost-Benefit Analysis; Dabigatran; Direct Service Costs; Enoxaparin; France; Humans; Italy; Models, Theoretical; Morpholines; Postoperative Complications; Pyridines; Quality of Life; Rivaroxaban; Spain; Thiophenes; Venous Thromboembolism

Patients receiving anticoagulants could be at higher risk of compressive haematoma with neuraxial anaesthesia use. The phase III RECORD programme compared rivaroxaban with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement surgery in more than 12,500 patients. This observational analysis evaluated the risk of neuraxial haematoma after neuraxial anaesthesia in patients receiving rivaroxaban or enoxaparin using pooled RECORD1-4 data.. The incidences of intraspinal bleeding or haemorrhagic puncture were recorded as part of the criteria for major bleeding (the primary safety outcome in the RECORD studies). Incidences of allogeneic transfusion and venous thromboembolism by type of anaesthesia were also recorded.. No compressive haematomas occurred in rivaroxaban-treated patients (10 mg once daily started 6-8 h after surgery) who underwent neuraxial anaesthesia (n = 4086). Among enoxaparin-treated patients (n = 4090), one compressive spinal haematoma requiring laminectomy occurred after epidural catheter removal in an elderly female patient with renal insufficiency undergoing total knee replacement. Total venous thromboembolism rates did not differ according to type of anaesthesia.. Although no issues were observed with the use of neuraxial anaesthesia in this population of 4086 patients receiving rivaroxaban after total hip or knee replacement, it is important to remain aware of the risk of compressive haematoma. This may be of particular concern in elderly patients with renal insufficiency receiving an anticoagulant predominantly eliminated via the kidneys.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Enoxaparin; Female; Hematoma; Humans; Incidence; Male; Middle Aged; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Deep vein thrombosis and its most dangerous outcome, pulmonary embolism, are complications with a high incidence in hospitalized patients. In plastic surgery, abdominoplasty is the aesthetic surgery more frequently associated with deep vein thrombosis condition. This study aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after abdominoplasty in patients considered to be at risk.. In a randomized, double-blind study, 40 patients undergoing abdominoplasty were assigned to receive either oral rivaroxaban (10 mg) or oral placebo once daily for 10 days, beginning 6 to 8 hours after surgery.. The study was interrupted after 27 operations due to systematic complications. The population operated on was composed of women with a mean age of 38 years. Most patients were Caucasian (85 percent) and had a mean body mass index of 28. The average overall rate of complications was 29.6 percent (large hematomas requiring drainage), and all complications were seen in the study group, with none in the control group.. Plastic surgery procedures in which large detachment is planned in patients with a moderate risk of deep venous thrombosis should be evaluated with regard to the risk and benefit of thromboembolism prophylaxis. Other measures must be applied and eventually contraindicate a surgical procedure. Further research is needed to complement the data from this work.

Topics: Abdominoplasty; Administration, Oral; Adult; Anticoagulants; Double-Blind Method; Drug Administration Schedule; Early Termination of Clinical Trials; Female; Follow-Up Studies; Hematoma; Humans; Middle Aged; Morpholines; Postoperative Care; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Pulmonary Embolism; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Venous Thrombosis

To explore the incidence of postoperative venous thromboembolism (VTE) in adult patients with primary bone tumor undergoing knee operation and evaluate its efficacy and safety in the prevention of VTE.. For this prospective, randomized and negative-control single-center trial, a total of 100 eligible patients were selected and randomly divided into observation and control groups. Observation group (rivaroxaban): the first rivaroxaban tablet was taken in the first 24 hours after operation. Rivaroxaban was administered daily every 24 hours up to Day 14.. no anticoagulant was taken postoperatively.. Efficacy indictors: 6 cases of DVT (an incidence of 12%) occurred in the observation group versus 15 (30%) in the control group. Significant statistical difference existed between two groups (P < 0.05). Furthermore, neither pulmonary embolism nor death was found in either group. Safety indicators:a total of 3 bleeding (1 major and 2 non-major) cases occurred in observation group versus a total of 2 bleeding (no major and 2 non-major) cases in control group. No significant statistical difference existed in bleeding events (P > 0.05). The total incidence of adverse effect was 6% (3/50) in the observation group. The drainage volume of the observation group was a little more than that of the control group. But no significant statistical difference existed in drainage duration (P > 0.05). And there was almost no change in the coagulation system by laboratory examination after oral administration.. With an excellent safety profile and a low incidence of adverse effects, Rivaroxaban is effective and safe in the prevention of VTE in adult patients with primary bone tumor undergoing knee operation.

Topics: Adult; Anticoagulants; Bone Neoplasms; Female; Humans; Knee; Male; Middle Aged; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Young Adult

This study aimed to evaluate the cost-effectiveness of prophylaxis with rivaroxaban vs. enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR) from the perspective of the Canadian healthcare system. A model was developed that included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with one-year cycles). Transition probabilities were derived from phase III clinical trials comparing rivaroxaban with enoxaparin and published literature. Costs were derived from the Ontario Case Costing Initiative and publicly available sources. Utilities were derived from published literature. The model reported VTE event rates, quality-adjusted life expectancy and direct medical costs over a five-year horizon. Costs are reported in 2007 Canadian Dollars (C$). When rivaroxaban and enoxaparin are compared in patients undergoing THR, rivaroxaban dominates enoxaparin. That is, rivaroxaban is associated with improved health outcomes as measured by increased quality-adjusted life years (QALYs; 0.0006) and fewer symptomatic VTE events (0.0061), and also with lower cost (savings of C$300) per patient. Similarly, rivaroxaban dominates enoxaparin in patients undergoing TKR, achieving a gain of 0.0018 QALYs, a reduction of 0.0192 symptomatic venous thromboembolic events and savings of C$129 per patient. Rivaroxaban is a cost-effective alternative to enoxaparin for VTE prophylaxis in patients undergoing THR and TKR. Over a five-year horizon, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more quality-of-life benefit at a lower cost.

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Canada; Cost-Benefit Analysis; Enoxaparin; Follow-Up Studies; Humans; Morpholines; Postoperative Complications; Quality of Life; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Venous Thromboembolism

Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking.. We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I²=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I²=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17; P<0.001; number needed to treat, 167; I²=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99; P=0.049; number needed to harm, 167; I²=0%).. In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Follow-Up Studies; Hemorrhage; Humans; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism; Withholding Treatment

Total hip/knee replacement surgeries are associated with an increased risk of venous thromboembolism and post-operative thromboprophylaxis has become standard treatment. This study aimed to: (i) assess the impact of hip/knee replacement surgery on ex vivo thrombin generation (TG), prothrombin fragments 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT) and D-dimer; (ii) compare the anticoagulant effects of dalteparin and rivaroxaban on TG 24 h after surgery. Haemostatic variables were assessed in plasma samples of 51 patients taken pre-operatively, peri-operatively, and 24 h post-operatively. Prophylaxis, once a day, with dalteparin or rivaroxaban, starting 6–8 h post-operatively, was administered in 25 (14 knee/11 hip) and 26 patients (13 knee/13 hip) respectively. TG, F1 + 2, TAT and D-dimer increased during surgery. Dalteparin patients showed a variable TG response 24 h after surgery: conversely, the effect of rivaroxaban on TG was consistent across individuals. Good correlation was seen between rivaroxaban levels and TG-lag-time (rs = 0·46, P = 0·01); TG-time-to-Peak (rs = 0·53, P = 0·005); TG-peak-thrombin (rs = −0·59, P = 0·001); and TG-velocity-index-rate (rs = −0·61, P = 0·0009). Patients who received rivaroxaban showed a greater decrease of TG, F1 + 2 and TAT (but not D-dimer) than those on dalteparin. TG increases during hip/knee replacement surgery. Rivaroxaban inhibits TG more than dalteparin at 24 h after surgery.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dalteparin; Factor Xa; Female; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Prospective Studies; Rivaroxaban; Thiophenes; Thrombin; Treatment Outcome; Venous Thromboembolism

Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban.. This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6-8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5-9 days after surgery.. A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint - deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality - occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant (p=0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban (p=0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban (p=0.0008), occurring in 0-10.8% of patients, compared with 0% in patients receiving enoxaparin.. This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Morpholines; Phlebography; Postoperative Complications; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography.. A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography.. Patients received study drugs until mandatory, bilateral venography was performed 7 +/- 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus.. A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively.. Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs.

Topics: Anticoagulants; Enoxaparin; Hip Prosthesis; Humans; Knee Prosthesis; Morpholines; Orthopedic Procedures; Phlebography; Postoperative Complications; Rivaroxaban; Sensitivity and Specificity; Thiophenes; Ultrasonography; Venous Thrombosis

Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants.. To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement.. In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery.. Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin.. When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Dose-Response Relationship, Drug; Double-Blind Method; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Thromboembolism; Venous Thrombosis

Rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders.. This randomized, double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n=873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and > or = 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=618, per-protocol population). No significant dose-response relationship was found for efficacy (P=0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=845, safety population), representing a significant dose-response relationship (P=0.0391).. Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.

Topics: Administration, Oral; Adult; Anticoagulants; Arthroplasty, Replacement, Hip; Double-Blind Method; Drug Administration Schedule; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Postmenopause; Postoperative Complications; Rivaroxaban; Safety; Sample Size; Survival Analysis; Thiophenes

Porto-mesenteric venous thrombosis (PMVT) is a significant complication that occurs more frequently after laparoscopic sleeve gastrectomy (SG) than other bariatric procedures and presents later than other venous thromboembolic (VTE) events often 2 weeks after the operation. The common current practice in bariatric surgery of perioperative chemoprophylaxis until discharge may not adequately prevent PMVT. Therefore, a 30-day post-discharge chemoprophylaxis (PDC) might reduce the incidence of PMVT. The objective of this study is to determine whether 30-day PDC with rivaroxaban 10 mg daily following SG can reduce the incidence of PMVT.. In a retrospective cohort study, 292 consecutive patients undergoing SG by a single surgeon were either prescribed rivaroxaban 10 mg daily for 30 days upon discharge (group A) or did not receive any PDC (group B). Primary outcome was PMVT and secondary outcome was bleeding. Patients on chronic anticoagulation therapy were excluded from the study.. PMVT events differences were significant between the groups while bleeding events were not. Group A had zero PMVT events, while group B had four (p = .045). There were 4 bleeding events in group A and 7 bleeding events on group B (p = .341).. A 30-day PDC regimen of rivaroxaban 10 mg daily is both safe and effective. This study demonstrated zero PMVT events without an increased risk of bleeding using this regimen.

Topics: Aftercare; Anticoagulants; Gastrectomy; Humans; Laparoscopy; Mesenteric Ischemia; Obesity, Morbid; Patient Discharge; Portal Vein; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis

BackgroundVenous thromboembolism (VTE) is common after bariatric surgery and extended prophylaxis is generally recommended. Low molecular weight heparin is the most commonly used agent but requires patients to be trained to self-inject and is expensive. Rivaroxaban is an oral daily formulation approved for VTE prophylaxis after orthopedic surgery. Efficacy and safety of rivaroxaban has been confirmed in major gastrointestinal resections by several observational studies. We report a single centre experience of using rivaroxaban as an agent for VTE prophylaxis in bariatric surgery. MethodsWe performed prospective cohort study assessing safety and efficacy of rivaroxaban as a medication for VTE prophylaxis in patients undergoing bariatric surgery in a single centre in Kyiv, Ukraine. Patients undergoing major bariatric procedure received perioperative prophylaxis of VTE with subcutaneous low molecular weight heparin and then were switched to rivaroxaban for total of 30 days starting on the 4th postoperative day. Thromboprophylaxis was performed in accordance with the VTE risks derived from the Caprini score. On the 3rd, 30th, 60th day after the operation, the patients underwent ultrasound examination of the portal vein, as well as the veins of the lower extremities. Telephone interviews were conducted 30 and 60 days after the surgery to evaluate the presence of complaints which may be characteristic for VTE as well as to assess compliance with the regimen and to assess patient satisfaction. Outcomes studies were incidence of VTE and adverse events related to rivaroxaban administration.Results110 patients were included in the study from July 2019 to May 2021. The average age of the patients was 43.6 years, the average preoperative BMI was 55 (35 to 75). One hundred and seven patients (97.3%) underwent laparoscopic intervention while three patients (2.7%) underwent laparotomy. Eighty-four patients underwent sleeve gastrectomy and twenty-six patients underwent other procedures, including bypass surgery. Average calculated risk of thromboembolic event was 5-6% based on Caprine index. All patients were treated with extended prophylaxis with rivaroxaban. The average follow-up period for patients was 6 months. There were no clinical or radiological evidence of thromboembolic complications in the study cohort. Overall complication rate was 7.2%, however, only one patient (0.9%) developed subcutaneous hematoma associated with rivaroxaban not requiring intervention. Co

Topics: Adult; Animals; Anticoagulants; Bariatric Surgery; Goats; Heparin, Low-Molecular-Weight; Humans; Postoperative Complications; Prospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Aftercare; Anticoagulants; Bariatric Surgery; Gastrectomy; Humans; Laparoscopy; Obesity, Morbid; Patient Discharge; Portal Vein; Postoperative Complications; Retrospective Studies; Rivaroxaban

In the VOYAGER PAD trial, rivaroxaban 2.5 mg plus aspirin significantly reduced the primary composite efficacy outcome of acute limb ischaemia, major amputation, myocardial infarction, ischaemic stroke, or cardiovascular death compared with aspirin alone. However, patients enrolled in the trial may not reflect patients encountered in daily clinical practice. This study described the proportion of patients eligible for VOYAGER PAD within the nationwide Danish Vascular Registry (DVR), reasons for ineligibility, and outcomes according to eligibility.. In total, 32 911 patients who underwent lower extremity revascularisation for symptomatic peripheral arterial disease (PAD) in the DVR (2000-2016) were identified. Trial inclusion and exclusion criteria were applied, and the three year cumulative incidence of primary and secondary trial outcomes was estimated.. Altogether, 27.1% of patients with PAD in the DVR were "VOYAGER eligible". Of those not included, 30.7% had at least one exclusion criterion ("VOYAGER excluded"), and an additional 42.3% did not fulfil the inclusion criteria ("VOYAGER not included"). The main reasons for exclusion were atrial fibrillation (32.3%), poorly regulated hypertension (20.6%), requirement for long term dual antiplatelet therapy (10.9%), cytochrome P450 inhibitors or inducers (9.7%), and renal failure (9.3%). The three year rate of the primary efficacy outcome was 10.08 per 100 person years among the "VOYAGER eligible", 16.32 among "VOYAGER excluded", and 6.98 among the "VOYAGER not included". For the primary safety outcome of thrombolysis in myocardial infarction (TIMI) major bleeding, rates were 2.24, 3.76, and 1.17, respectively. Rates of secondary endpoints were also consistently lower for patients who did not meet the inclusion criteria (predominantly due to central aorto-iliac procedures) and highest for "VOYAGER excluded" patients. "VOYAGER eligible" patients experienced a higher cumulative incidence of most endpoints than patients enrolled in the control arm of the VOYAGER PAD trial.. Among patients in routine clinical practice, 27.1% were eligible for the VOYAGER PAD trial. These patients were older, had more severe vascular symptoms, higher bleeding risk, and worse prognosis than trial participants.

Topics: Aged; Aspirin; Clinical Trials, Phase III as Topic; Denmark; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Treatment Outcome; Vascular Surgical Procedures

To explore the cohort study of rivaroxaban combined with D-dimer dynamic monitoring in the prevention of deep venous thrombosis (DVT) after knee arthroplasty.. Eighty-four patients with knee osteoarthritis who went through total knee arthroplasty from June 2019 to June 2021 in our hospital were arbitrarily assigned into the study group and the control group. The patients in the control group were cured with rivaroxaban anticoagulation after operation, and the study group was cured with dynamic monitoring of D-dimer on the basis of the control group. The incidence of postoperative DVT, pulmonary embolism (PE), and bleeding complications (incision ecchymosis and bleeding events) were compared. The related indexes such as drainage volume and blood transfusion volume were compared. The levels of activated partial prothrombin time (APPT), prothrombin time (PT), and D-dimer were dynamically monitored before and after operation. Visual analogue scale (VAS) was adopted to assess the degree of postoperative incision pain, the level of limb swelling before and after operation was measured, the circumference difference of affected limb was calculated, the ecchymosis area was assessed in the form of nine-palace grid, and the scores were compared.. According to the comparison of VAS score, there exhibited no remarkable difference before operation and on the first day after operation, but the VAS score decreased after operation, and the VAS score of the study group on the 3rd day, 7th day, and 14th day after operation was remarkably lower compared to the control group (. Rivaroxaban combined with D-dimer dynamic monitoring has high clinical value in preventing DVT after knee arthroplasty and can effectively reduce the amount of blood loss during operation and the incidence of postoperative DVT, PE, and bleeding complications, which is worth popularizing to reduce the area of ecchymosis and the degree of pain after operation and shorten the recovery process.

Topics: Arthroplasty, Replacement, Knee; Cohort Studies; Ecchymosis; Fibrin Fibrinogen Degradation Products; Humans; Pain; Postoperative Complications; Rivaroxaban; Venous Thrombosis

Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model.. The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective.. The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates.. Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.

Topics: Ankle; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Chemoprevention; Cost-Benefit Analysis; Enoxaparin; Humans; Postoperative Complications; Rivaroxaban; Venous Thromboembolism; Warfarin

There were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.. We performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.. Apixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban.. Apixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Topics: Aged; Anticoagulants; Blood Transfusion; Cohort Studies; Colonic Polyps; Colonoscopy; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hong Kong; Humans; Male; Postoperative Complications; Pyrazoles; Pyridones; Retrospective Studies; Risk Assessment; Rivaroxaban; Thromboembolism; Warfarin

The aim of this study is to compare the effectiveness and safety of thromboprophylactic treatments in patients undergoing primary total knee arthroplasty (TKA).. Using nationwide medical registries, we identified patients with a primary TKA performed in Denmark between 1 January 2013 and 31 December 2018 who received thromboprophylactic treatment. We examined the 90-day risk of venous thromboembolism (VTE), major bleeding, and all-cause mortality following surgery. We used a Cox regression model to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, pairwise comparing treatment with dalteparin or dabigatran with rivaroxaban as the reference. The HRs were both computed using a multivariable and a propensity score matched analysis.. We identified 27,736 primary TKA patients who received thromboprophylactic treatment (rivaroxaban (n = 18,846); dalteparin (n = 5,767); dabigatran (n = 1,443); tinzaparin (n = 1,372); and enoxaparin (n = 308)). In the adjusted multivariable analysis and compared with rivaroxaban, treatment with dalteparin (HR 0.68 (95% CI 0.49 to 0.92)) or dabigatran (HR 0.31 (95% CI 0.13 to 0.70)) was associated with a decreased risk of VTE. No statistically significant differences were observed for major bleeding or all-cause mortality. The propensity score matched analysis yielded similar results.. Treatment with dalteparin or dabigatran was associated with a decreased 90-day risk of VTE following primary TKA surgery compared with treatment with rivaroxaban. Cite this article:

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antithrombins; Arthroplasty, Replacement, Knee; Dabigatran; Dalteparin; Denmark; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Proportional Hazards Models; Registries; Rivaroxaban; Tinzaparin; Venous Thromboembolism; Young Adult

Reducing the incidence of venous thromboembolism (VTE) following abdominal body contouring surgery remains a top priority for patient safety. There is a lack of consensus regarding the optimal chemoprophylactic agent for postoperative VTE prophylaxis, and the role of oral anticoagulants warrants further investigation.. The aim of this multisurgeon, single-institution study was to determine the safety and efficacy of a 7-day postoperative rivaroxaban regimen for VTE prophylaxis in abdominal body contouring surgery.. A retrospective chart review was performed of all patients who underwent abdominoplasty, circumferential body lift, fleur-de-lis panniculectomy, or circumferential fleur-de-lis panniculectomy at our surgical center from August 2014 to November 2019. A 7-day postoperative course of once-daily 10 mg rivaroxaban, starting on postoperative day 1, was administered to every patient unless there was a contraindication. The 2 primary endpoints were the incidence of VTE and bleeding events.. A total of 600 patients were included in the study. There were no deaths. There were 4 (0.7%) incidents of VTE events: 2 (0.3%) patients suffered pulmonary embolus and 2 (0.3%) patients suffered a lower-extremity deep venous thrombosis. A total of 13 (2.2%) patients suffered complications related to bleeding. Of these, operative intervention for control and evacuation was required in 7 (1.2%) patients.. A 7-day postoperative course of once-daily rivaroxaban for VTE risk reduction in abdominal body contouring surgery is associated with a low incidence of VTE events and a low risk of bleeding complications.

Topics: Anticoagulants; Body Contouring; Humans; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD.. We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin.. Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding.. The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.

Topics: Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Endoscopic Mucosal Resection; Female; Humans; Japan; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stomach; Stomach Neoplasms; Thiazoles; Thromboembolism; Warfarin

The safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) for the treatment of venous thromboembolism (VTE) have been established in randomized controlled trials, but limited data are available on their use in clinical practice across geographical regions.. In the international RE-COVERY DVT/PE observational study (enrollment January 2016 to May 2017), we sought to characterize the patient population and describe the prescribed anticoagulant. Patient characteristics and anticoagulants administered after objective diagnosis of VTE were recorded at the baseline visit and again at hospital discharge or at 14 days after the diagnosis, whichever was later.. A total of 6095 patients were included, 50.2% were male, and the mean age was 61.5 years. The most common comorbidities were hypertension (35%), diabetes mellitus (11%), cancer (11%), prior VTE(11%), and trauma/surgery (7%). Overall, 77% of patients received oral anticoagulants, with 54% on NOACs and 23% on vitamin K antagonists (VKAs); 20% received parenteral anticoagulation only. NOACs comprised about 60% of anticoagulant treatment in Europe and Asia but substantially less in Latin America (29%) and the Middle East (21%). For NOAC therapies, the distribution (as a percentage of the total cohort) was rivaroxaban 25.6%, dabigatran 15.5%, apixaban 11.3%, and edoxaban 1.7%. Treatment with NOACs was less frequent in patients who had cancer, chronic renal disease, heart failure, or stroke.. These findings enhance our understanding of baseline characteristics and the initial management of patients with VTE in routine practice.

Topics: Administration, Oral; Adult; Age Distribution; Aged; Anticoagulants; Asia; Comorbidity; Cross-Sectional Studies; Dabigatran; Diabetes Mellitus; Europe; Factor Xa Inhibitors; Female; Fondaparinux; Heparin; Humans; Hypertension; Latin America; Male; Middle Aged; Middle East; Neoplasms; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

Background The risk of venous thromboembolism following major orthopaedic surgery is among the highest for all surgical specialties. Our hospital guidelines for thromboprophylaxis following elective primary total hip or knee replacement are based on American College of Chest Physicians guidance. The most recent change to local guidelines was the introduction of the extended aspirin regimen as standard thromboprophylaxis. Objective To establish the appropriateness of this regimen by comparing venous thromboembolism rates in patients receiving extended aspirin to previous regimens. Setting The largest dedicated orthopaedic hospital in Ireland. Methods This was a retrospective cohort study. Data were collected from patient record software. All eligible patients undergoing primary total hip or knee replacement between 1st January 2010 and 30th June 2016 were included. Main outcome measure Venous thromboembolism up to 6 months post-operatively. Results Of the 6548 participants (55.3% female, mean age 65.4 years (± 11.8 years, 55.8% underwent total hip replacement), venous thromboembolism occurred in 65 (0.99%). Venous thromboembolism rate in both the inpatient enoxaparin group (n = 961) and extended aspirin group (n = 3460) was 1.04% and was 0.66% in the modified rivaroxaban group (n = 1212). Non-inferiority analysis showed the extended aspirin regimen to be equivalent to the modified rivaroxaban regimen. History of venous thromboembolism was the only significant demographic risk factor for post-operative venous thromboembolism (0.87% vs. 3.54%, p  = 0.0002). Conclusion In daily clinical practice, extended aspirin regimen is at least as effective as modified rivaroxaban for preventing clinically important venous thromboembolism among patients undergoing hip or knee arthroplasty who are discharged from the hospital without complications. Aspirin can be considered a safe and effective agent in the prevention of venous thromboembolism after total hip or total knee replacement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Delayed-Action Preparations; Elective Surgical Procedures; Enoxaparin; Female; Humans; Ireland; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Socioeconomic Factors; Venous Thromboembolism; Young Adult

We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient's risk of VTE.. Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality.. Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities.. Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article:

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Aspirin; Chemoprevention; Early Ambulation; Elective Surgical Procedures; Female; Follow-Up Studies; Heparin; Heparin, Low-Molecular-Weight; Humans; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Venous Thromboembolism; Warfarin

There is little data on management and outcomes of atrial fibrillation (AF) patients on direct oral anticoagulants (DOAC) undergoing general surgery.We retrospectively assessed 98 surgeries in 85 nonvalvular AF patients aged 73 ± 8 (59 men) receiving DOACs. Cardiac, emergency, and minimally invasive surgeries were excluded.The CHA

Topics: Aged; Aged, 80 and over; Antithrombins; Atrial Fibrillation; Blood Loss, Surgical; Carotid Artery Diseases; Cerebral Infarction; Dabigatran; Digestive System Surgical Procedures; Elective Surgical Procedures; Embolism; Endoscopy; Factor Xa Inhibitors; Female; Humans; Male; Myocardial Infarction; Orthopedic Procedures; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Thiazoles; Thromboembolism; Urologic Surgical Procedures; Vascular Surgical Procedures

It's estimated that 40% to 60% of patients undergoing major orthopedic surgery of the hip or knee who do not receive thromboprophylaxis will develop deep venous thrombosis Instituto Nacional de Traumatologia e Ortopedia has established a guideline to prevent DVT with the administration of the Enoxaparin. Recently, institute stakeholders have been questioning this guideline as new oral anticoagulants that offer more comfort and efficacy, but present higher risk of bleeding, have been appearing in the market for treating deep venous thrombosis.. This study aims to validate the application of a multicriteria decision analysis in a real-world problem, the use of rivaroxaban and enoxaparin to prevent deep venous thrombosis.. The multicriteria method MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) was used in a decision conferencing process to develop an evaluation model for measuring the relative value of the drugs on each evaluation criterion, separately and globally. The model-building process was informed by a literature review and meta-analysis of randomized clinical trials with a critical appraisal of the evidence.. We report a model-structure with eight criteria, each one associated with a weighting coefficient and value function. Following a simple additive aggregation process, the model-outputs showed that Rivaroxaban was considered a robust option for DVT. Sensitivity analysis and robustness analysis were performed and testify the consistency of the results.. This article contributes to literature by showing how MACBETH method can be combined with scientific evidence and participatory group processes, for health technology assessment in hospitals.

Topics: Anticoagulants; Brazil; Enoxaparin; Hemorrhage; Humans; Orthopedic Procedures; Pharmaceutical Preparations; Postoperative Complications; Rivaroxaban; Venous Thrombosis

<b>Purpose: </b>Venous thromboembolism (VTE) after colorectal surgery is a well-documented complication, resulting in a general recommendation of extended post-discharge prophylaxis. Rivaroxaban, a factor Xa inhibitor, is a daily tablet approved for treatment of VTE and prophylaxis after orthopedic surgery. <br><b>Aim: </b>The purpose of this study is to evaluate the safety of rivaroxaban for extended prophylaxis after major abdominal and pelvic surgery. <br><b>Methods: </b>This is a retrospective review of patients undergoing major colorectal surgery at a regional hospital in Kiev, Ukraine. Patients received peri-operative VTE prophylaxis with subcutaneous heparin and then transitioned to rivaroxaban for a total of 30 days. Occurrences of major or minor bleeding, blood transfusion, and a need for re-intervention were noted. Phone surveys were administered on post-operative day 30 to assess compliance and satisfaction with the regimen. <br><b>Results: </b>A total of 51 patients were included in the study with an average age of 62.4 years. Seventy-one percent of the cases were abdominal, 29% were pelvic cases and 59% were done laparoscopically. There was one episode of major intra-abdominal bleeding requiring return to the operating room. There were 2 minor bleeding episodes which did not require intervention. There were no VTE events in the group. The phone survey response rate was 100%. All but one patient reported having completed the full course of rivaroxaban. Patients reported that oral prophylaxis was easy to adhere to and preferable compared to injections. <br><b>Conclusion: </b>Implementation of extended prophylaxis with rivaroxaban is easy, safe and does not increase rates of postoperative bleeding.

Topics: Aftercare; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Rivaroxaban; Time Factors; Treatment Outcome; Venous Thromboembolism

Although several studies now support the use of aspirin for venous thromboembolism (VTE) prophylaxis in primary total hip arthroplasty (THA) and total knee arthroplasty (TKA), the optimal chemoprophylactic agent in revision THA and TKA is not clear. The purpose of this study was to determine if the type of chemoprophylaxis has an effect on the VTE rate in patients undergoing revision total joint arthroplasty (TJA). The second aim was to compare differences in rates of wound drainage in primary and revision TJA stratified by the postoperative chemoprophylaxis used. The authors retrospectively reviewed 1917 consecutive patients undergoing primary and revision TJA. Individual records were reviewed for patient demographics, medical comorbidities, type of chemoprophylaxis, VTE risk factors, intraoperative data, and postoperative complications. Outcomes, including VTE rate and wound complications, were compared between types of anticoagulant therapy used postoperatively. Of the 1917 patients, there were 742 (38.7%) primary TKAs, 326 (17%) revision TKAs, 608 (31.7%) primary THAs, and 241 (12.6%) revision THAs. The most common prophylactic agent used was rivaroxaban (40.6%), followed by warfarin (28.5%) and aspirin (27.6%). Type of chemoprophylaxis was not associated with postoperative VTE or wound drainage (P>.05). Although revision surgery was an independent risk factor for wound drainage (odds ratio, 3.201; 95% confidence interval, 1.594-6.426; P=.001), it was not a risk factor for VTE (odds ratio, 1.847; 95% confidence interval, 0.423-8.053; P=.414). Revision arthroplasty alone was not associated with an increased rate of VTE. Aspirin is as effective as other chemoprophylactic agents without the increased risk of bleeding in low-risk patients. [Orthopedics. 2019; 42(6):323-329.].

Topics: Adult; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Reoperation; Retrospective Studies; Risk Factors; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin

Leakage of bone cement from femoral medullary cavity is a rare complication after hip arthroplasty, and there is no report on the leaked bone cement entering into iliac vessels.. An 89-year-old woman presented with a fracture in the right femoral neck. She had well-fixed right femoral head replacement after careful preoperative examinations, and no adverse reactions appeared. She was able to get off bed to walk at the 2nd day after surgery.. Postoperative radiograph showed leakage of bone cement into the joint through femoral medullary cavity entering into iliac vessels, but the patient complained no discomforts. She received a treatment with low-molecular weight heparin and rivaroxaban.. The patient was able to walk with normal gait, without swelling in both lower extremities and discomfort in the hip. There was no other complication concerning intravascular foreign bodies.. This case calls into the phenomenon of leakage of injected bone cement in femoral head replacement regardless of complete and nonfractured femur, which may be into the lower limb and pelvic veins, given that, dangerous consequences will not occur.

Topics: Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Bone Cements; Factor Xa Inhibitors; Female; Femur Head; Heparin, Low-Molecular-Weight; Humans; Iliac Vein; Postoperative Complications; Radiography; Rivaroxaban; Treatment Outcome

To compare the efficacy and safety of aspirin with rivaroxaban following treatment with enoxaparin for prevention of venous thromboembolism (VTE) after hip fracture surgery (HFS).. A total of 390 patients were enrolled in the trial. According to an odd or even number at the end of their registration number, the patients were divided into the aspirin group (n = 198) and the rivaroxaban group (n = 192). All patients were given enoxaparin subcutaneous injection after the operation and returned to the routine dose the next day until postoperative day five. The patients in the aspirin group received an additional 16 days of thromboprophylaxis with 100 mg of aspirin once daily. The rivaroxaban group was assigned to receive an additional 16 days of thromboprophylaxis with 10 mg of oral rivaroxaban once daily. Patients were followed for 90 days regarding VTE and bleeding complications.. The incidence of VTE in the aspirin group and rivaroxaban group was 6.6% (13/198) and 5.7% (11/192), respectively (P = 0.83). The rate of major bleeding events occurred in two (1.0%) patients in the aspirin group and in one patient (0.5%) in the rivaroxaban group (P = 1.0). A combination of major bleeding and clinically relevant nonmajor bleeding occurred in five patients (2.5%) in the aspirin group and in six patients (3.1%) in the rivaroxaban group (P = 0.77). During the 90-day follow-up, a pulmonary embolism developed in one patient (0.5%) in the aspirin group and none in the rivaroxaban group (P = 1.0).. Extended prophylaxis for 21 days with aspirin was equivalent to the direct oral anticoagulant rivaroxaban after hip fracture surgery with an initial 5-day postoperative course of enoxaparin. Aspirin may be an effective, safe, convenient, and cheap alternative for extended prophylaxis after hip fracture surgery.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Drug Therapy, Combination; Enoxaparin; Female; Hip Fractures; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Topics: Arthroplasty, Replacement, Knee; Aspirin; Humans; Postoperative Complications; Rivaroxaban; Thromboembolism

Novel oral anticoagulants (NOACs) are being increasingly used in the secondary prevention of thromboembolic stroke in patients with atrial fibrillation. Patients taking NOACs are difficult to manage perioperatively, and several unexpected complications have been reported in these patients.. We report a case of a rivaroxaban-induced retroperitoneal haematoma in a 72-year-old man who underwent an L5/S1 anterior lumbar interbody fusion (ALIF) for grade 1 spondylolytic spondylolisthesis. The patient suffered from atrial fibrillation and was taking rivaroxaban, a factor Xa inhibitor, for thromboembolic risk reduction. In accordance with perioperative Novel Oral Anticoagulant (NOAC) guidelines, rivaroxaban was stopped 2 days preoperatively and restarted on the third postoperative day. The patient presented on the ninth postoperative day, complaining of severe left iliac fossa pain, nausea, and vomiting, accompanied by swelling and bruising around the surgical site. A computed tomography (CT) scan showed a large expanding retroperitoneal haematoma. The patient was taken back to theatre for an evacuation of the haematoma and subsequently recovered without any further complications.. This is the first case of a rivaroxaban-induced retroperitoneal haematoma reported in the literature, secondary to elective spinal surgery. This report adds to the body of evidence on the risk of postoperative bleeding in patients taking NOACs. If patients on NOACs present with abdominal symptoms following anterior approach to the lumbar spine, treating clinicians should have a high index of suspicion for retroperitoneal haematoma.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Factor Xa Inhibitors; Hematoma; Humans; Lumbar Vertebrae; Male; Postoperative Complications; Postoperative Hemorrhage; Retroperitoneal Space; Rivaroxaban; Spondylolisthesis; Stroke; Thromboembolism

The purpose of this study was to evaluate whether anticoagulation (warfarin or direct oral inhibitors) affected the success of endovenous treatment.. Patients taking anticoagulation (warfarin or direct oral inhibitors) undergoing endovenous treatment in the form of endovenous laser ablation (EVLA) were matched against controls for sex, age, leg, and vein. Data were collected prospectively between January 2012 and March 2017. The primary endpoint was failure of treatment at 6-week postoperative duplex scan. The rates of major bleeding, hematoma, endothermal heat-induced thrombosis, venous thromboembolism, or pulmonary embolism were also compared between groups.. Two hundred eighty-four limbs underwent EVLA during the study period. Of this, 23/284 (8.1%) procedures were done in patients on anticoagulation. 21/23 (91.3%) limbs had venous occlusion at follow-up compared with 23/23 (100%) of controls ( P = .49). The patient who failed treatment in the anticoagulation group had undergone small saphenous vein (SSV) ablation. There was no difference in the complication rates between groups.. This study demonstrates that anticoagulation does not affect success rates of EVLA though there was higher recanalization rate in patients undergoing SSV ablation. Anticoagulation can be continued safely in patients undergoing this procedure.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation; Endovascular Procedures; Factor Xa Inhibitors; Female; Humans; Laser Therapy; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Retrospective Studies; Risk Factors; Rivaroxaban; Saphenous Vein; Time Factors; Treatment Outcome; Venous Insufficiency; Warfarin

In recent years, the concept of treatment after surgery in the department of orthopedics has changed from hemostasis to anticoagulant. This article analyses the safety and effectiveness of anticoagulants for prophylactic anticoagulants after spinal fractures. By analyzing the incidence of bleeding and VTE in 2 weeks after operation, there was no significant difference between the 2 groups (P>0.05), but the incidence of VTE in rivaroxaban group was significantly lower than that in control group. In conclusion, the rivaroxaban oral anticoagulants are stable, safe and easy to use. It significantly reduced the incidence of VTE after spinal fracture and nerve injury, and did not increase the risk of bleeding. It is an ideal type of prophylactic anticoagulant after the operation of spinal fracture, which is worthy of further clinical study.

Topics: Fracture Fixation, Internal; Humans; Postoperative Complications; Retrospective Studies; Rivaroxaban; Spinal Fractures; Thrombosis

To assess association between 30 day readmission rate and treatment received after total hip and knee arthroplasty (THA/TKA) discharge (rivaroxaban vs. warfarin or non-anticoagulant). To subsequently model impact of increasing rivaroxaban use on the Hospital Readmission Reduction Program (HRRP) penalty, which was imposed on hospitals with excess 30 day readmissions after hospitalizations for selected conditions, including THA/TKA.. The US Truven Health MarketScan Medicare Supplemental database from 1 July 2010 to 30 April 2015 was used. A retrospective claims analysis was conducted to assess the risk of all-cause 30 day readmission among patients receiving either rivaroxaban or warfarin, or no anticoagulation following THA/TKA discharge. Simulations were performed to estimate the impact of post-discharge treatment on the HRRP penalty.. The risk-adjusted all-cause 30 day readmission rates were 1.21% (95% confidence interval [95% CI]: 0.94%-1.49%), 1.41% (95% CI: 1.19%-1.58%) and 1.95% (95% CI: 1.81%-2.11%) for rivaroxaban, warfarin and non-anticoagulant cohorts, respectively. Using these rates, simulations illustrated that when switching patients from warfarin or non-anticoagulant to rivaroxaban, annual penalty per hospital would be reduced up to 67% or 88%, respectively.. Rivaroxaban treatment post-THA/TKA discharge reduced the risk of 30 day readmission compared to non-anticoagulants. Simulations illustrated that increasing rivaroxaban use could decrease the HRRP penalty.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Humans; Insurance Claim Review; Male; Medicare; Patient Discharge; Patient Readmission; Postoperative Complications; Retrospective Studies; Rivaroxaban; United States; Warfarin

Topics: Aspirin; Atherosclerosis; Atrial Fibrillation; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Receptors, Purinergic P2Y12; Rivaroxaban; Thrombosis

Patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are at high risk of deep vein thrombosis (DVT) postoperatively, necessitating the use of prophylaxis medications. This investigation used a large claims database to evaluate trends in postoperative DVT prophylaxis and rates of DVT within 6 months after THA or TKA.. Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases were reviewed from 2004 to 2013 for patients who underwent THA or TKA. Data were collected on patient age, sex, Charlson Comorbidity Index, and hypercoagulability diagnoses. Postoperative medication claims were reviewed for prescribed aspirin, warfarin, enoxaparin, fondaparinux, rivaroxaban, and dabigatran.. A total of 369,483 patients were included in the analysis, of which 239,949 patients had prescription medication claims. Warfarin was the most commonly prescribed anticoagulant. Patients with a hypercoagulable diagnosis had markedly more DVTs within 6 months after THA or TKA. More patients with a hypercoagulable diagnosis were treated with warfarin or lovenox than other types of anticoagulants. A multivariate regression analysis was performed, showing that patients prescribed aspirin, fondaparinux, and rivaroxaban were markedly less likely than those prescribed warfarin or enoxaparin to have a DVT within 6 months after THA or TKA.. After THA and TKA, warfarin is the most commonly prescribed prophylaxis. Patients with hypercoagulability diagnoses are at a higher risk of postoperative DVT. The likelihood of DVT within 6 months of THA and TKA was markedly higher in patients treated with warfarin and lovenox and markedly lower in those treated with aspirin, fondaparinux, and rivaroxaban.. Level III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Decision-Making; Dabigatran; Databases, Factual; Enoxaparin; Female; Fondaparinux; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thrombosis; Warfarin

Ecchymosis is a common complication after total knee arthroplasty (TKA). However, only a few studies have been conducted to determine the coagulation status of these patients. Using thromboelastography (TEG), a new technique recording the viscoelastic changes of a whole-blood sample, this study was performed to understand the ecchymosis-related coagulation status and its risk factors.. Seventy-five patients receiving unilateral TKA were recruited in this observational study. Oral rivaroxaban was applied as prophylaxis treatment after surgery. TEG was performed 1 day before surgery and 4 days after surgery. Total blood loss and hidden blood loss were recorded and calculated. Univariate and multivariate analyses were conducted to determine risk factors.. Twenty-five patients (33.3%) developed ecchymosis within 2-3 days after TKA. Compared with the baseline before TKA, the α-angle (P = .032) and calculated coagulation index (CI; P = .012) were increased in non-ecchymosis group, whereas in the ecchymosis group, there was no significant difference regarding any variable of postoperative TEG evaluation. The ecchymosis group exhibited more hidden blood loss (P = .007) and total blood loss (P = .011). Value change of CI (OR = 0.666, 95% confidence interval = [0.496, 0.895], P = .007) and hidden blood loss (OR = 1.008, 95% confidence interval = [1.002, 1.013], P = .004) were recognized as the independent risk factors for postoperative ecchymosis.. In TEG evaluation, the value change of CI and hidden blood loss are independent risk factors of ecchymosis. In view of the relative hypocoagulation status, it is reasonable to stop anticoagulation therapy in patients with excessive ecchymosis. Personalized anticoagulation therapy may be helpful for managing ecchymosis after TKA.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Contraindications, Drug; Ecchymosis; Female; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Rivaroxaban; Thrombelastography

The present study estimates the effect of rivaroxaban on preventing deep vein thrombosis (DVT) in aged diabetics with femoral neck fractures after hip replacement. Our study consisted of 236 aged diabetics with femoral neck fractures, which were divided into the rivaroxaban and control groups. Reaction time (R time), clot formation time (K time), α angle (α), maximum amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. DVT was diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were analysed by logistic regression analysis. Compared with the control group, in the rivaroxaban group, R time and K time were extended and α, MA and G decreased 1 day before operation. One day after operation, the rivaroxaban group had less PT and APPT and lower incidence of DVT than the control group. In the two groups, preoperative and postoperative PT and APPT significantly differed. Body mass index (BMI) ≥25, abnormal coagulation indicators, use of cemented femoral hip prosthesis, high haemoglobin content and non-ankle pump exercise after operation were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics with femoral neck fractures after hip replacement.

Topics: Aged; Arthroplasty, Replacement, Hip; Blood Coagulation; Body Mass Index; Diabetic Angiopathies; Female; Femoral Neck Fractures; Humans; Logistic Models; Male; Partial Thromboplastin Time; Postoperative Complications; Postoperative Period; Preoperative Period; Prothrombin Time; Reaction Time; Risk Factors; Rivaroxaban; Venous Thrombosis

Data evaluating the impact of the periprocedural administration of novel oral anticoagulants (NOACs) on complications in the setting of pulmonary vein (PV) isolation using cryoballoon (CB) is limited. In the present study, our aim was to analyze procedural characteristics and incidence of complications in those patients who underwent CB ablation for atrial fibrillation and the impact of NOACs on adverse events compared with vitamin K antagonists (VKAs). Consecutive patients with drug resistant atrial fibrillation who underwent PV isolation by CB as index procedure were retrospectively included in our analysis. In group I, 290 of 454 patients (63.9%) received VKAs (warfarin: n = 222 and acenocoumarol: n = 68), and in group II, 164 of 454 patients (36.1%) were treated with NOACs (rivaroxaban: n = 71; dabigatran: n = 60; and apixaban: n = 33). Age was significantly higher in the group II (62.8 ± 9.7 vs 58.6 ± 11.3; p <0.001). During the study period, 454 consecutive patients (male 71%, age 60.1 ± 10.9 years) were enrolled. Major complications occurred in 9 patients (2.0%): peripheral vascular complications were observed in 6 patients (1.3% per procedure), persistent phrenic nerve palsy occurred in 2 (0.4%), and transient ischemic attacks in 1 (0.2%). In both groups, the incidence of major complications was similar (group I [VKAs]: 7 patients [2.4%] vs group II [NOACs]: 2 patients [1.2%]; p = 0.5). In conclusion, CB ablation is a safe procedure for PV isolation and is associated with low complication rates. The incidence of adverse events in PV isolation using the second-generation CB with the periprocedural administration of NOACs is not significantly different than VKA treatment.

Topics: Ablation Techniques; Administration, Oral; Anticoagulants; Antithrombins; Atrial Fibrillation; Belgium; Cryosurgery; Dabigatran; Dose-Response Relationship, Drug; Drug Therapy, Combination; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Incidence; Intraoperative Period; Italy; Male; Middle Aged; Postoperative Complications; Prognosis; Pyrazoles; Pyridines; Pyridones; Retrospective Studies; Rivaroxaban; Stroke; Survival Rate; Thiazoles; Time Factors; Vitamin K

Limited data is available regarding the pharmacological prophylaxis for venous thromboembolism (VTE) in Asian patients undergoing total knee arthroplasty or total hip arthroplasty (TKA/THA).. We performed a population-based epidemiological study using the Health Insurance Review and Assessment Service database to estimate the rate of pharmacological thromboprophylaxis and its impact on VTE in Korean patients who underwent TKA/THA between 2009 and 2013.. We identified 306,912 cases (TKA, 261,260; THA, 45,652). The pharmacological thromboprophylaxis rate was 57.16% (TKA, 58.32%; THA, 50.51%), which increased from 42.81% in 2009 to 65.92% in 2013 (P = 0.0165). Both low-molecular-weight-heparin (22.42%) and rivaroxaban (22.71%) were the most common drugs for prophylaxis. The number of patients aged ≥ 60 years (87.31% vs. 81.01%, P < 0.0001), cases requiring general anesthesia (20.70% vs. 18.37%, P < 0.0001), and cases requiring long hospital stay (median, 13 days vs. 12 days, P < 0.0001) were significantly greater in the pharmacological prophylaxis group. The incidence of VTE within 3 months of surgery was 1.52% (TKA, 1.46%; THA, 1.87%). Patients with pharmacological prophylaxis had higher VTE rates (TKA, 1.69% vs. 1.14%; THA, 2.30% vs. 1.43%) than those without prophylaxis, with advanced age, use of general anesthesia, and a longer hospital stay increasing the risk of VTE. However, rivaroxaban significantly reduced the incidence of VTE following TKA (0.82% vs. 1.14%; odd ratio [OR], 0.72; 95% CI, 0.65-0.79). Moreover, ≥ 10 days of pharmacological thromboprophylaxis was significantly associated with lower incidence of VTE after TKA (1.33% vs. 1.52%; OR, 0.87; 95% CI, 0.81-0.94).. This represents the largest epidemiological study showing a gradual increase in the use of pharmacological prophylaxis in Korean patients undergoing TKA/THA. Although the incidence of VTE is still low without pharmacological prophylaxis, this study demonstrates that the incidence of VTE can be reduced further using appropriate pharmacological thromboprophylaxis strategies.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Erythrocyte Transfusion; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Polysaccharides; Postoperative Complications; Postoperative Hemorrhage; Republic of Korea; Risk Factors; Rivaroxaban; Venous Thromboembolism

Endovenous heat-induced thrombosis (EHIT) is a well-described complication of endovenous laser ablation (EVLA). We report our centers' experience on the efficacy (EHIT level ≥2 according to the Kabnick classification) and safety (observed major and minor bleeding events) of rivaroxaban for EHIT prophylaxis in EVLA with and without concomitant phlebectomy.. Demographic, procedural, and outcome data of all patients with EVLA of the great, accessory, or small saphenous vein and EHIT prophylaxis with 10 mg/d rivaroxaban between 2012 and 2014 were reviewed and analyzed in this investigator-initiated multicenter retrospective observational single-arm study.. During a median (interquartile range) follow-up duration of 51 (41-68) days, complete vein occlusion was achieved in 98.4% of 438 EVLA procedures in 306 patients. One patient had an EHIT level 2 (0.2%; 95% confidence interval, 0.006%-1.3%). No major bleedings (0%; 95% confidence interval, 0.0%-0.8%) and six minor bleedings (1.4%; 95% confidence interval, 0.5%-3%) were observed.. Rivaroxaban (10 mg/d) for 5 to 10 days seems to be an efficacious and safe alternative for EHIT prophylaxis in EVLA with or without phlebectomy.

Topics: Adult; Aged; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Laser Therapy; Male; Middle Aged; Popliteal Vein; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Saphenous Vein; Switzerland; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Varicose Veins; Vascular Surgical Procedures; Venous Insufficiency

Topics: Adult; Breast Implantation; Female; Forearm; Hand; Humans; Postoperative Complications; Rivaroxaban; Stockings, Compression; Thrombophlebitis; Ultrasonography, Doppler, Color

Topics: Administration, Oral; Amiodarone; Atrial Fibrillation; Drug Administration Schedule; Drug Therapy, Combination; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Parotid Gland; Perioperative Care; Phenprocoumon; Postoperative Complications; Pulmonary Embolism; Rivaroxaban

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Dabigatran; Female; Humans; Male; Middle Aged; Mohs Surgery; Postoperative Complications; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban

Few data exist to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) undergoing cryoballoon ablation (CB-A). This study is aimed to clarify the usefulness of DOACs in patients undergoing CB-A.. The patients (average age; 65.8±11.9 years old, male 69%) were stratified into one of five subsets based on the type of anticoagulation (warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban), and underwent CB-A. A brain MRI was performed in all patients the day after the CB-A for AF. A total of 257 (19 on warfarin, 30 on apixaban, 66 on dabigatran, 81 on rivaroxaban, and 61 on edoxaban) patients met the inclusion criteria.. The incidence of silent cerebral ischemic lesion was 1 (11.1%) patients on warfarin, 5 (33.3%) on apixaban, 8 (27.6%) on dabigatran, 10 (21.3%) on rivaroxaban, and 10 (29.4%) on edoxaban (p=0.17). Major ischemic events occurred in one patient (1.6%) on edoxaban and one (5.3%) on warfarin. Minor bleeding complications occurred in 1 patient (5.3%) on warfarin, 2 (6.7%) on apixaban, 1 (1.2%) on rivaroxaban, 5 (7.6%) on dabigatran, and 2 (3.3%) on edoxaban (p=0.24). Of note, major bleeding complications occurred in 2 patients (3.3%) on apixaban, 1 (1.2%) on rivaroxaban, 1 (1.5%) on dabigatran, 1 (1.6%) on edoxaban, and 2 (10.5%) on warfarin (p<0.05).. Warfarin use significantly increased the risk of serious bleeding, in contrast, CB-A did not place the patients at an increased risk of complications under a DOAC treatment. There were no significant differences regarding preventing embolic events among the DOAC drugs.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Brain; Brain Ischemia; Cryosurgery; Dabigatran; Embolism; Female; Hemorrhage; Humans; Incidence; Magnetic Resonance Imaging; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Warfarin

Thromboprophylaxis is a controversial and challenging topic in joint replacement surgery. Mechanical prophylaxis in combination with the use of anticoagulants have been shown to have greater efficacy than single modalities. But the early use of anticoagulants has the potential to increases the risk of postoperative bleeding. The purpose of this study was to evaluate the thromboprophylactic effects of sequential combined method using early-mechanical compression with delayed rivaroxaban in total knee arthroplasty. A retrospective cohort study, including 369 patients receiving simultaneous combined mechanical and pharmacological thromboprophylactic modality and 385 patients receiving sequential combined modality with early-mechanical compression treatment followed by rivaroxaban 2 days later after primary total knee arthroplasty surgery was conducted. The incidence rates of proximal and distal deep vein thrombosis (DVT) on the 2nd day and the 5th week and the volume of wound drainage were compared postoperatively. On the 2nd postoperative day, the incidence rates of proximal and distal DVT in the sequential group (1.56, 4.16%) had no significant difference compared with those (1.08, 3.25%) in the simultaneous group (

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Combined Modality Therapy; Female; Humans; Incidence; Intermittent Pneumatic Compression Devices; Male; Middle Aged; Postoperative Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Treatment Outcome; Venous Thrombosis

This study investigated the effectiveness and the outcomes of rivaroxaban vs the standard of care for venous thromboembolic prophylaxis in patients undergoing fracture-related surgery. A total of 413 patients undergoing fracture-related surgery from 9 Swiss orthopedic and trauma centers were enrolled. The authors selected the type of venous thromboembolic prophylaxis according to standardized medical practice at the participating centers before the inclusion of patients: 208 patients received rivaroxaban and 205 received the standard of care. Data on symptomatic thromboembolic and bleeding events, surgery-related complications, death, adverse events, time to mobilization, and hospital discharge were collected. Symptomatic thromboembolic events were reported in 1 patient (0.5%) and 2 patients (1.0%) and treatment-emergent major bleeding events were reported in 1 patient (0.5%) and 2 patients (1.0%) receiving rivaroxaban and the standard of care, respectively. The durations of hospital stay and venous thromboembolic prophylaxis were similar in the 2 groups. In both groups, adverse events related to venous thromboembolic prophylaxis were reported in 12 patients. The proportion of patients with minor and major fracture surgery was 74.3% and 25.7%, respectively. In patients undergoing minor fracture surgery receiving rivaroxaban (n=167) and the standard of care (n=140), no symptomatic thromboembolic events and no major bleeding events were reported. Outcomes of this study indicate that rivaroxaban might be an appropriate oral alternative for venous thromboembolic prophylaxis in routine medical care after fracture-related major and minor surgery. Reported results were comparable to those from other large-scale, noninterventional and randomized controlled studies. [Orthopedics. 2017; 40(2):109-116.].

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Factor Xa Inhibitors; Female; Fracture Fixation; Fractures, Bone; Humans; Male; Middle Aged; Perioperative Care; Postoperative Complications; Rivaroxaban; Switzerland; Treatment Outcome; Venous Thromboembolism; Young Adult

The aim of this study was to evaluate the cost-effectiveness of rivaroxaban and apixaban versus enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after total hip replacement (THR).. A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the three prophylactic strategies for Chinese patients after THR. Transition probabilities for acute VTE were derived from two randomized controlled studies, RECORD1 and ADVANCE3, of patients after THR. The transition probabilities of long-term complications after acute VTE, utilities, and costs were derived from the published literature and local healthcare settings. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. The quality-adjusted life years (QALYs) and direct medical costs were reported over a 5-year horizon, and incremental cost-effectiveness ratios (ICERs) were also calculated.. Thromboprophylaxis with apixaban was estimated to have a higher cost (US $178.70) and more health benefits (0.0025 QALY) than thromboprophylaxis with enoxaparin over a 5-year time horizon, which resulted in an ICER of US $71,244 per QALY gained and was more than three times the GDP per capita of China in 2014 (US $22,140). Owing to the higher cost and lower generated QALYs, rivaroxaban was inferior to enoxaparin among post-THR patients. The sensitivity analyses confirmed these results.. The analysis found that apixaban was not cost-effective and that rivaroxaban was inferior to enoxaparin. This finding indicates that compared with enoxaparin, the use of apixaban for VTE prophylaxis after THR does not represent a good value for the cost at the acceptable threshold in China; in addition, the cost of rivaroxaban was higher with lower QALYs.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; China; Cost-Benefit Analysis; Decision Trees; Enoxaparin; Humans; Long Term Adverse Effects; Postoperative Complications; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism

To evaluate the occurrence of bleeding and venous thromboembolic (VTE) events in patients receiving rivaroxaban, warfarin, or warfarin with the addition of enoxaparin during the immediate postoperative period following major orthopedic surgery.. Patients older than 18 years who received at least one dose of rivaroxaban the morning following surgery, adjusted dose warfarin, or adjusted dose warfarin with the addition of enoxaparin for VTE prophylaxis after major orthopedic surgery between October 1, 2011, and February 28, 2015, were included. Data collected from the electronic health record included patient demographics, renal function, inpatient aspirin, P2Y12 inhibitor and/or nonsteroidal antiinflammatory drug (NSAID) use, type of surgery, postoperative analgesia, and presence of VTE risk factors. Adjusted incidence rate ratio for bleeding or VTE events was estimated using modified Poisson regression with robust standard errors. Covariates included in a multivariable model were age, sex, aspirin use, P2Y12 inhibitor use, NSAID use, obesity, VTE risk factors, and creatinine clearance.. There were 3246 patients who met study inclusion criteria. Overall, incidences of bleeding and VTE events were rare. Bleeding event incidence ranged from 0.4% in the warfarin and warfarin with the addition of enoxaparin groups to 1.2% in the rivaroxaban group (p=0.088). There were two major bleeding events and 18 minor bleeding events (including hemorrhagic wound complications). VTE event incidence ranged from 0.2% in the warfarin with the addition of enoxaparin group to 0.6% in the rivaroxaban group (p=0.230). Two deep vein thromboses and 10 pulmonary emboli occurred. With use of the multivariable model, the warfarin and warfarin with the addition of enoxaparin groups had significantly lower incidence rates of bleeding compared with rivaroxaban (incidence rate ratio [IRR] = 0.218, p=0.0120, and IRR = 0.242, p=0.021, respectively).. We observed a small, yet significant, increase in rivaroxaban-related bleeding in the immediate postoperative period relative to warfarin or warfarin with the addition of enoxaparin for the prevention of VTE after major orthopedic surgery.

Topics: Aged; Anticoagulants; Dose-Response Relationship, Drug; Drug Therapy, Combination; Enoxaparin; Factor Xa Inhibitors; Female; Hemorrhage; Hospitals, Community; Humans; Male; Middle Aged; Orthopedic Procedures; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Warfarin

Abdominoplasty, a commonly performed aesthetic procedure, is considered to have an increased risk of venous thromboembolism (VTE) events. At present, routine VTE chemoprophylaxis following abdominoplasty remains controversial.. This study evaluates the authors' experience with rivaroxaban, an oral Factor Xa inhibitor, for VTE prophylaxis in abdominoplasty patients.. A retrospective case series was conducted. All patients who underwent abdominoplasty and received rivaroxaban were included. The prophylactic dose was 10 mg daily for 7 days, beginning 12 hours postoperatively. Patient demographics, comorbidities, and type of surgery were recorded. The primary outcome measured was hematologic complication, including VTE, hematoma requiring operative evacuation, and need for blood transfusion.. From September 2012 until July 2014, 132 patients (122 women and 10 men) underwent abdominoplasty surgery and received rivaroxaban postoperatively. Mean patient age was 43.7 years, and mean body mass index was 27.1. One hundred twenty-five patients also underwent abdominal muscle plication. Eleven patients underwent a fleur de lis vertical skin resection component. One hundred patients underwent concomitant abdominal liposuction, while 79 patients also had back liposuction. Only 1 patient had a symptomatic VTE event. Three patients had a hematoma requiring operative evacuation, and all went on to heal without sequelae. Two patients received a blood transfusion for anemia during their course of rivaroxaban.. Oral rivaroxaban administration for chemoprophylaxis in abdominoplasty patients is safe, with low rates of symptomatic VTE and hematoma formation. The authors continue routine use of the medication for patients at increased risk for VTE events. LEVEL OF EVIDENCE 4: Risk.

Topics: Abdominoplasty; Adult; Aged; Factor Xa Inhibitors; Female; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism; Young Adult

Topics: Abdominoplasty; Anticoagulants; Humans; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

Data on the novel oral anticoagulants (NOACS) during catheter ablation (CA) of atrial fibrillation (AF) are still limited. This study evaluated the periprocedural major complications (MC) of CA of AF, and compared Apixaban, Dabigatran, and Rivaroxaban with continuous phenoprocoumon.. A total of 444 patients (mean age = 65.1 ± 9.4 years; 283 [64%] male) with paroxysmal (n = 180 [41%]), persistent (n = 256 [58%]), or longstanding-persistent AF were enrolled. CA was performed in all patients using radiofrequency energy in conjunction with a 3D-mapping system. MCs were defined according to the current guidelines. Continuous phenprocoumon-therapy was administered in 120/444 (27%) patients (group 1) and 324/444 (73%) patients were treated with NOACs (group 2; Dabigatran: n = 51 [15.7%]; Rivaroxaban: n = 193 [59.6%]; Apixaban: n = 80 [24.7%]). Procedure times were comparable between groups 1 and 2 (128.2 ± 39.7 minutes vs. 129.7 ± 51.2 minutes; P = 0.77). CHA2 DS2-Vasc (3.0 [2.0, 4.0)] vs. 2.0 [1.0, 3.0]; P < 0.01) and HASBLED scores (2.0 [2.0, 2.5] vs. 2.0 [1.0, 2.0]; P = 0.002) were higher in group 1 patients. The incidence of MCs in the overall group was 8/444 (2%) and was equally distributed between groups 1 and 2 (2/120 [2%] vs. 6/324 [2%], P = 0.90). The incidence of MCs was comparable between the three different NOACs. There were no significant differences between patients with and without MCs with regard to age, CHA2 DS2-Vasc-score or HASBLED-score.. The major complication rate between all three NOACs currently available and continuous phenprocoumon during AF ablation seem to be comparable. Complication rates were similar between patients treated with the three different available NOACs.

Topics: Action Potentials; Administration, Oral; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Drug Administration Schedule; Electrophysiologic Techniques, Cardiac; Factor Xa Inhibitors; Female; Heart Rate; Humans; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Pyrazoles; Pyridones; Registries; Rivaroxaban; Stroke; Time Factors; Treatment Outcome

The second-generation multi-electrode-phased radiofrequency pulmonary vein ablation catheter (PVAC GOLD(®)) was redesigned with the intent to improve its safety and efficacy.. Using a prospectively designed single-centre database, we retrospectively analysed 128 consecutive patients (102 paroxysmal and 43 female) who underwent their first pulmonary vein isolation with the PVAC GOLD(®). The analysis focused on procedural data as well as in-hospital complications. Baseline characteristics of the patient collective were as follows: mean age 57.9 years, mean CHA2DS2-VASC was 1.73 ± 1.30; structural heart disease was present in seven patients. The PVAC GOLD(®) exhibited procedure durations of 123.1 min ± 27.9, duration of energy delivery was 18.3 min ± 11.4, and fluoroscopy duration was 16.0 min ± 7.7. The redesigned catheter shows major complication [major bleeding, transitory ischaemic attack (TIA), and pericardial tamponade] rates of 2.3% (n = 3). The overall rate of adverse events was 5.4% (n = 7). Bleeding complications were observed in three patients (2.3%), in particular there were two cases (1.6%) of minor bleeding and one case (0.8%) of major bleeding. Two patients suffered pericardial effusion, but there was no need for pericardiocentesis. Besides one TIA, there was no other thrombo-embolic event. Furthermore, one case of post-procedural fever was observed. No deaths, stroke, or haemorrhagic shock occurred. Of the 510 pulmonary veins, 508 could be reached with the PVAC GOLD(®) device using a non-steerable long sheath.. The PVAC GOLD(®) seems to have an acceptable safety profile. The handling is comparable with the previous generation PVAC(®).

Topics: Aged; Antithrombins; Atrial Fibrillation; Catheter Ablation; Dabigatran; Databases, Factual; Electrodes, Implanted; Equipment Design; Europe; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Postoperative Complications; Pulmonary Veins; Retrospective Studies; Rivaroxaban; Treatment Outcome

Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB.. PVI was performed using second-generation CB by two experienced investigators. A total of 409 patients (58.9% male; mean age = 61 ± 10 years) with atrial fibrillation were included in this study. In group I, 150/409 (36.7%) patients received phenprocoumon therapy, and in group II, 259/409 (63.3%) patients were treated with NOACs (rivaroxaban: n = 193; dabigatran: n = 48; and apixaban: n = 18). In both groups, the rates of major complications were similar (group I [phenprocoumon]: four pts (2.7%) vs. Group II [NOACs]: seven pts (2.7%); P = 0.999). In this cohort, 275 patients were ablated with the bonus freeze protocol, and 134 patients were ablated without bonus freezes. The procedure duration significantly decreased with the bonus freeze protocol from 102.3 ± 24.6 min to 68.5 ± 16.2 min (P < 0.001). The impact of the bonus freeze on the postprocedural increase of C-reactive protein (CRP) levels was significant compared to the postprocedural CRP levels after procedures without the bonus freeze protocol (postprocedural CRP level+ bonus protocol: 1.6 ± 1.2 mg/L vs. postprocedural CRP level+ nonbonus protocol: 1.3 ± 1.3 mg/L; P = 0.04).. The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon. Further, large-scale randomized studies are needed to evaluate the safety of two anticoagulation regimes comparing vitamin K antagonists and NOACs, as well as different NOAC regimes, in patients undergoing PVI using cryoballoon ablation.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Biomarkers; Cryosurgery; Dabigatran; Female; Germany; Humans; Incidence; Inflammation Mediators; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Pulmonary Veins; Pyrazoles; Pyridones; Retrospective Studies; Rivaroxaban; Treatment Outcome

Following orthopaedic surgery, a 56-year-old woman developed heparin-induced thrombocytopenia (HIT), complicated by extensive proximal deep vein thrombosis. The patient did not respond to multiple conventional therapies; however, a prompt treatment response occurred after starting rivaroxaban at standard dosing. This case represents the first documentation of efficacy for rivaroxaban in the setting of treatment refractory HIT and strengthens the limited existing evidence for this agent in HIT.

Topics: Anticoagulants; Drug Resistance; Factor Xa Inhibitors; Female; Heparin; Humans; Middle Aged; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thrombocytopenia; Venous Thrombosis

Evidence from clinical trials shows rivaroxaban to be effective for the treatment of deep vein thrombosis. Switching to rivaroxaban following failure of indirect anticoagulants in deep vein thrombosis has not been demonstrated in a real-life setting.. A 43-year-old white woman was switched from warfarin to rivaroxaban for the treatment of thrombosis of her right common femoral vein after saphenectomy. The reason for the switch was due to the instability of anti-coagulation therapy with vitamin K antagonists over a period of 3 months during which she did not reach the "therapeutic range" of prothrombin time-international normalized ratio. The ineffectiveness of the conventional oral anticoagulant was confirmed by persistence of moderate-high values of fibrin D dimers (780 ng/ml) and by residual vein thrombosis at an ultrasound examination. Objectively, her right leg appeared to be still edematous and warm and pain was elicited by deep palpation. Rivaroxaban was administered after warfarin discontinuation (prothrombin time-international normalized ratio = 1.43) at a dosage of 15 mg every 12 hours for 3 weeks, followed by 20 mg once daily for 3 months. After this period, her objective symptoms significantly improved, with reduction of edema of her lower limb and pain relief. Her fibrin D dimer values returned to normal (210 ng/ml). An ultrasound showed recanalization of the obstructed venous segment.. In this case report, a switch to rivaroxaban from warfarin was shown to be effective and safe for the treatment of postoperative deep vein thrombosis, whereas standard oral anticoagulation therapy, which required dose adjustments over a period of 3 months, was not able to stabilize the therapeutic range of prothrombin time-international normalized ratio nor improve our patient's outcome.

Topics: Adult; Anticoagulants; Drug Administration Schedule; Female; Humans; Lower Extremity; Postoperative Complications; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin

Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Humans; Lung Transplantation; Male; Postoperative Complications; Rivaroxaban

Novel oral anticoagulant (NOAC) agents dabigatran, rivaroxaban, and apixaban are increasingly utilized as thromboembolic prevention for patients with atrial fibrillation undergoing direct current cardioversion (DCCV) with post hoc analyses of clinical trials suggesting satisfactory safety and efficacy. This study characterizes utilization, effectiveness, and complications of NOAC agents for stroke prophylaxis in the setting of DCCV.. Comparison of warfarin and NOAC agents as periprocedural anticoagulation for DCCV procedures performed at Cleveland Clinic from January 2009 through December 2013. Variables of interest include utilization rates for each NOAC agent stratified by clinical parameters including CHADS2 score, and associated clinical outcomes including cerebrovascular accident (CVA), transient ischemic attack (TIA), peripheral arterial embolism (PAE), and bleeding events during 8 weeks of postprocedure follow-up.. Among 5,320 DCCV procedures, 673 (12.6%) cases were excluded due to inadequate follow-up. Warfarin was utilized in 3,721 (80.1%), dabigatran in 719 (15.5%), rivaroxaban in 159 (3.4%), and apixaban in 48 (1.0%) with a steady increase in NOAC utilization from 2011 to 2013. There were low rates of CVA/TIA (warfarin: 0.97% vs NOAC 1.62%, P = 0.162) and bleeding (warfarin: 1.02% vs NOAC: 0.5%, P = 0.247) and no significant differences detected between agents. Higher CHADS2 /CHA2 DS2 -VASC scores were associated with thromboembolic and bleeding risk. Increasing age, chronic kidney disease, diabetes, coronary disease, and deep vein thrombosis/pulmonary embolism were associated with increased bleeding risk.. In a high-volume, single-center experience, NOAC utilization has grown to account for over a third of cardioversion procedures, and these agents appear safe and effective compared to warfarin with low rates of thromboembolic and bleeding complications.

Topics: Administration, Oral; Aged; Anticoagulants; Dabigatran; Defibrillators, Implantable; Female; Hemorrhage; Humans; Ischemic Attack, Transient; Male; Middle Aged; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin

Topics: Coronary Disease; Factor Xa Inhibitors; Female; Humans; Male; Percutaneous Coronary Intervention; Postoperative Complications; Rivaroxaban; Thrombosis

Although data from the Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1-4 trials have shown a similar postoperative bleeding risk between rivaroxban and enoxaparin in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), anecdotal observations from local institutions have suggested that postoperative bleeding rates seemed higher in patients who received rivaroxaban than those reported in the RECORD trials. Thus, the objective of this pilot study was to assess postoperative bleeding events observed in clinical practice in patients receiving rivaroxaban after undergoing THA and TKA and to compare their results with those published in the RECORD trials.. Retrospective cohort study with a comparator group of patients from the RECORD 1-4 trials.. Two institutions within a regional health care system.. Four hundred forty adults who received at least one dose of rivaroxaban 10 mg daily after undergoing THA or TKA in the two institutions between August 2011 and October 2013 (cohort group), and 6183 patients who received rivaroxaban in the RECORD 1-4 trials (comparator group).. Postoperative bleeding was assessed in the cohort patients versus the patients in the RECORD trials. The primary outcome, occurrence of any postoperative bleeding, was a composite of major and clinically relevant nonmajor bleeding as defined in the RECORD trials. Any postoperative bleeding occurred in 6.8% of the cohort patients versus 3.2% of the RECORD trial patients (p<0.0001); 1.4% of the cohort patients versus 0.38% of the RECORD trial patients suffered a major bleed (p=0.013). Within defined major bleeding, bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin level decrease of at least 2 g/dl or transfusion of 2 units or greater of packed red blood cells were reported in 0.68% versus 0.19% (p=0.073) and 0.68% versus 0.13% (p=0.032), respectively, of the cohort patients versus the RECORD trial patients.. Overall, any postoperative bleeding in the cohort patients occurred significantly more frequently than that observed in the RECORD trial patients. The major bleeding rate was also significantly higher in the cohort patients, influenced by higher rates of bleeding leading to reoperation and clinically overt extrasurgical site bleeding resulting in either a hemoglobin decrease of at least 2 g/dl or transfusion of two units or greater of packed red blood cells. These findings from our pilot study are thought provoking and, thus, invite further investigation.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Clinical Trials as Topic; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Rivaroxaban; Venous Thromboembolism

Deep-vein thrombosis and subsequent pulmonary embolism are major complications in total joint arthroplasty of the lower limbs. New oral anticoagulants are increasingly prescribed as thromboprophylaxis due to their simple administration and encouraging phase III marketing studies.. In this observational study, we compared the efficacy and safety of rivaroxaban with nadroparin in 1302 unselected patients receiving hip or knee arthroplasty.. Venous thrombembolism occurred in 3.3% (2.3%; 4.7%, 95% CI, n = 838) of patients receiving rivaroxaban and in 4.3% (2.7%; 6.7%, 95% CI, n = 464) of patients receiving nadroparin resulting in an absolute risk reduction (ARR) of 1.0% (-1.4%; 3.3%, 95% CI).. With an odds ratio of 0.6 (0.4; 1.0, 95% CI), rivaroxaban was associated with a decreased perioperative drop in haemoglobin exhibiting an improved thromboprophylactic profile when compared to high dose nadroparin. Furthermore, transfusion rates were 8.8% (-2.7%; 19.9%, 95% CI) lower in patients receiving rivaroxaban. However, as previous studies have shown, low preoperative haemoglobin remains the most predictive factor for postoperative transfusions (OR: 2.4 [1.3; 4.4, 95% CI]).

Topics: Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Causality; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Germany; Humans; Male; Middle Aged; Nadroparin; Postoperative Complications; Prevalence; Risk Factors; Rivaroxaban; Survival Rate; Treatment Outcome; Venous Thromboembolism

According to guidelines, initiation of pharmacological thromboprophylaxis after total knee or hip replacement is recommended and associated with improved patient outcomes. However, data on how these recommendations are followed in clinical practice are sparse.. All patients undergoing first-time total knee or hip replacement in Denmark 2008-2011 were identified. By cross-referencing Danish nationwide registries, quantitative use of anticoagulants administered orally and subcutaneously post-discharge was assessed by number of claimed prescriptions after surgery. Logistic regression analysis was used to identify factors associated with initiation of prophylaxis.. A total of 50,389 patients were included in the study (median age 69, inter-quartile range 62-76). Novel oral anticoagulants were initiated in 14.7 % of the patients and heparins/fondaparinux in 2.3 % of the patients. The use of anticoagulants increased from 6.3 % in 2008 to 30.0 % of patients in 2011. Among patients initiating prophylaxis with a novel oral anticoagulant post-discharge, almost all were treated according to guidelines in terms of treatment duration. Factors significantly associated with an increased chance of prophylaxis among total hip replacement patients were: age (per 10-year increments) and female gender.. Use of pharmacological thromboprophylaxis after total knee or hip replacement was low, but increasing during the study period. This is probably due to increased availability of novel oral anticoagulants. Further initiatives to increase guideline recommended use of prophylactic anticoagulation after orthopaedic surgery are warranted.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Dabigatran; Denmark; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Quality Improvement; Registries; Retrospective Studies; Risk Assessment; Rivaroxaban; Statistics, Nonparametric; Survival Rate; Treatment Outcome; Venous Thromboembolism

A case of serum sickness or serum sicknesslike reaction (SSLR) in a patient receiving rivaroxaban for venous thromboembolism (VTE) prophylaxis after undergoing elective right total knee arthroplasty (TKA) is reported.. A 61-year-old man arrived at the emergency department from a short-term rehabilitation facility 12 days after a right TKA with complaints of fever, chills, bilateral forearm pain, swelling in the extremities, and a diffuse erythematous rash with welts on his back. Rivaroxaban was initiated on postoperative day 1 for VTE prophylaxis and was discontinued on day 10 of therapy, when symptoms began to appear. His renal function was within normal limits; however, his alanine transaminase level was twice the upper limit of normal. The patient was admitted to the inpatient medical service and placed on intravenous fluids, subcutaneous heparin for VTE prophylaxis, supportive therapy for his symptoms, and his home medications. After 2 days of observation, the rheumatology and immunology services were consulted to assess the patient. Due to the patient's fever, myalgias, mild transaminitis, diffuse erythematous rash, and depressed total serum complement, it was determined that the patient had serum sickness secondary to treatment with rivaroxaban. The patient did not require any acute interventions, and symptoms resolved after 4 days of hospitalization.. A 61-year-old man developed a possible case of serum sickness or SSLR 10 days after initiation of rivaroxaban for VTE prophylaxis after an elective TKA. Symptomatic improvement was observed after discontinuation of rivaroxaban, and no acute interventions were needed.

Topics: Arthroplasty, Replacement, Hip; Factor Xa Inhibitors; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Serum Sickness; Treatment Outcome; Withholding Treatment

To evaluate the efficacy and safety of three antithrombotic agents on venous thromboembolism (VTE) after unilateral total knee arthroplasty.. From November 2011 to March 2014, 149 patients undergoing unilateral total knee arthroplasty for knee osteoarthritis were reviewed. Among them, there were 66 males and 83 females, ranging in age from 48 to 76 years old. All the cases were randomly divided into three groups including Aspirin group, low-molecular-weight heparin (LMWH) group, and rivaroxaban group, according to antithrombotic agents. Deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding complication (including wound ecchymosis, hematoma and other local complications, gastrointestinal, cardiovascular, urinary hemorrhage and other major bleeding events) of antithrombotic agents were observed and analyzed statistically at the 6 week, 8 week, and 12 week after operation.. Among patients who received Aspirin (48 cases), 4 patients had DVT, in 1 patient had PE, and 2 patients had bleeding complication. Among 54 patients in low-molecular-weight heparin group, 3 patients had DVT, 1 patient had PE, and 3 patients had bleeding complication. While among those patients received the rivaroxaban (47 cases), 3 patients had DVT, 0 patient had PE, and 11 patients had bleeding complication. There were no statistically differences among three groups on DVT, and PE (P>0.05). The incidence of bleeding complication in rivaroxaban group was higher than the other two antithrombotic agents, and the difference among the three groups was statistically significant (P<0.05).. Aspirin, low-molecular-weight heparin, and rivaroxaban could effectively reduce the incidence of VTE after total knee arthroplasty, and their efficacy was similar. Rivaroxaban has a higher incidence of bleeding complication and further clinical trials are required to be conducted to assess the safety of rivaroxaban in clinical.

Topics: Aged; Arthroplasty, Replacement, Knee; Aspirin; Case-Control Studies; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Postoperative Complications; Rivaroxaban; Venous Thromboembolism

The new direct-acting anticoagulants such as dabigatran and rivaroxaban are usually not monitored but may be associated with haemorrhage, particularly where renal impairment occurs. They have no effective "antidotes". We studied 17 patients receiving dabigatran 150 mg twice daily for non-valvular atrial fibrillation and 15 patients receiving rivaroxaban 10 mg daily for the prevention of deep venous thrombosis after hip or knee replacement surgery. We assessed the effect of these drugs on commonly used laboratory tests and Calibrated Automated Thrombogram (CAT) using plasma samples. We also assessed effects in fresh whole blood citrated patient samples using thromboelastography on the TEG and the ROTEM. The efficacy of nonspecific haemostatic agents prothrombin complex concentrate (PCC), Factor VIII Inhibitor By-passing Activity (FEIBA) and recombinant activated factor VII (rVIIa) were tested by reversal of abnormal thrombin generation using the CAT. Concentrations added ex vivo were chosen to reflect doses normally given in vivo. Dabigatran significantly increased the dynamic parameters of the TEG and ROTEM and the lag time of the CAT. It significantly reduced the endogenous thrombin potential (ETP) and reduced the peak height of the CAT. Rivaroxaban did not affect the TEG and ROTEM parameters but did increase the lag time and reduce ETP and peak height of the CAT. For both drugs, these parameters were significantly and meaningfully corrected by PCC and FEIBA and to a lesser but still significant extent by rFVIIa. These results may be useful in devising a reversal strategy in patients but clinical experience will be needed to verify them.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Automation, Laboratory; Benzimidazoles; beta-Alanine; Blood Coagulation Factors; Dabigatran; Equipment and Supplies; Factor VII; Hemorrhage; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Stroke; Thiophenes; Thrombelastography; Thrombin; Thrombin Time; Venous Thrombosis; Withholding Treatment

The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation.. Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown.. We performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period.. A total of 642 patients were included in the study, with 321 in each group. Mean age was 63 ± 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 ± 1.0 vs. 1.47 ± 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days.. Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morpholines; Perioperative Period; Postoperative Complications; Prospective Studies; Registries; Rivaroxaban; Thiophenes; Thromboembolism; Treatment Outcome

To compare the effect on blood loss after total knee arthroplasty (TKA) between rivaroxaban and enoxaparin.. A retrospective analysis was made on the clinical data of 107 patients (121 knees) with osteoarthritis undergoing primary TKA between January 2010 and October 2012. According to different perioperative anticoagulants, the patients were divided into the rivaroxaban group (51 cases, 57 knees) and the enoxaparin group (56 cases, 64 knees). There was no significant difference in gender, age, height, weight, body mass index, osteoarthritis classification, and disease duration between 2 groups (P > 0.05). The total blood loss, hidden blood loss, dominant blood loss, and the percentage of hidden blood loss were compared between 2 groups. The bleeding events were recorded within 35 days after operation.. The dominant blood loss of enoxaparin group was significantly higher than that of rivaroxaban group (t = 3.025, P = 0.003), but the percentage of hidden blood loss of enoxaparin group was significantly lower than that of rivaroxaban group (t = 4.361, P = 0.000); no significant difference was found in the total blood loss and hidden blood loss between 2 groups (P > 0.05). The incidence of bleeding event in rivaroxaban group (15.69%; including 1 case of incision bleeding, 4 cases of melena, and 3 cases of haematuria) was significantly higher than that in enoxaparin group (3.57%; including 1 case of haematuria and 1 case of melena) (chi2 = 4.624, P = 0.032).. Rivaroxaban does not increase the risk of hidden blood loss for TKA when compared with enoxaparin, but enoxaparin can increase the risk of dominant blood.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Volume; Enoxaparin; Female; Humans; Male; Middle Aged; Morpholines; Osteoarthritis, Knee; Postoperative Complications; Retrospective Studies; Risk Factors; Rivaroxaban; Thiophenes; Treatment Outcome

The determination of rivaroxaban and apixaban from serum samples of patients may be beneficial in specific clinical situations when additional blood sampling for plasma and thus the determination of factor Xa activity is not feasible or results are not plausible.. The primary aim of this study was to compare the concentrations of rivaroxaban and apixaban in serum with those measured in plasma. Secondary aims were the performance of three different chromogenic methods and concentrations in patients on treatment with rivaroxaban 10 mg od (n = 124) or 20 mg od (n = 94) or apixaban 5 mg bid (n = 52) measured at different time.. Concentrations of rivaroxaban and apixaban in serum were about 20-25% higher compared with plasma samples with a high correlation (r = 0·79775-0·94662) using all assays (all P < 0·0001). The intraclass correlation coefficients were about 0·90 for rivaroxaban and 0·55 for apixaban. Mean rivaroxaban concentrations were higher at 2 and 3 h compared with 1 and 12 h after administration measured from plasma and serum samples (all P-values < 0·05) and were not different between 1 vs. 12 h (plasma and serum).. The results indicate that rivaroxaban and apixaban concentrations can be determined specifically from serum samples.

Topics: Administration, Oral; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Atrial Fibrillation; Biological Assay; Case-Control Studies; Chromogenic Compounds; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Serum; Specimen Handling; Thiophenes; Thromboembolism

Topics: Aged; Atrial Fibrillation; Cardiac Tamponade; Catheter Ablation; Echocardiography, Doppler; Follow-Up Studies; Humans; Male; Morpholines; Pericardiocentesis; Pleural Effusion; Postoperative Complications; Rare Diseases; Rivaroxaban; Thiophenes; Time Factors; Treatment Outcome

Atrial fibrillation ablation requires peri-procedural oral anticoagulation (OAC) to prevent thromboembolic events. There are several options for OAC. We evaluate peri-procedural AF ablation complications using a variety of peri-procedural OACs.. We examined peri-procedural OAC and groin, bleeding, and thromboembolic complications for 2334 consecutive AF ablations using open irrigated-tip radiofrequency (RF) catheters. Pre-ablation OAC was warfarin in 1113 (47.7%), dabigatran 426 (18.3%), rivaroxaban 187 (8.0%), aspirin 472 (20.2%), and none 136 (5.8%). Oral anticoagulation was always interrupted and intraprocedural anticoagulation was unfractionated heparin (activated clotting time, ACT = 237 ± 26 s). Pre- and post-OAC drugs were the same for 1591 (68.2%) and were different for 743 (31.8%). Following ablation, 693 (29.7%) were treated with dabigatran and 291 (12.5%) were treated with rivaroxaban. There were no problems changing from one OAC pre-ablation to another post-ablation. Complications included 12 (0.51%) pericardial tamponades [no differences for dabigatran (P = 0.457) or rivaroxaban (P = 0.163) compared with warfarin], 12 (0.51%) groin complications [no differences for rivaroxaban (P = 0.709) and fewer for dabigatran (P = 0.041) compared with warfarin]. Only 5 of 2334 (0.21%) required blood transfusions. There were two strokes (0.086%) and no transient ischaemic attacks (TIAs) in the first 48 h post-ablation. Three additional strokes (0.13%), and two TIAs (0.086%) occurred from 48 h to 30 days. Only one stroke had a residual deficit. Compared with warfarin, the neurologic event rate was not different for dabigatran (P = 0.684) or rivaroxaban (P = 0.612).. Using interrupted OAC, low target intraprocedural ACT, and irrigated-tip RF, the rate of peri-procedural groin, haemorrhagic, and thromboembolic complications was extremely low. There were only minimal differences between OACs. Low-risk patients may remain on aspirin/no OAC pre-ablation. There are no problems changing from one OAC pre-ablation to another post-ablation.

Topics: Administration, Oral; Aged; Algorithms; Anticoagulants; Aspirin; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Catheter Ablation; Combined Modality Therapy; Dabigatran; Female; Heparin; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Radio Waves; Rivaroxaban; Thiophenes; Thromboembolism; Warfarin

To evaluate the safety and efficacy of rivaroxaban for prevention of deep vein thrombosis (DVT) in patients with preoperative abnormal D-dimer after total knee arthroplasty (TKA).. Between August and September 2013, 60 consecutive patients with varus knee osteoarthritis undergoing unilateral TKA were enrolled in the study. According to the preoperative D-dimer level, the patients were divided into 2 groups: D-dimer normal group (control group, n = 41) and D-dimer abnormal group (test group, n = 19). No significant difference was found in gender, age, body mass index, and preoperative knee range of motion between 2 groups (P > 0.05). All patients underwent conventional primary TKA and anticoagulation therapy with rivaroxaban to prevent DVT. The tourniquet use time, postoperative hospitalization time, and total hospitalization time were compared between 2 groups. At 1, 3, and 5 days after operation, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), and D-dimer were measured. Wound complications and DVT were observed.. The postoperative hospitalization time of the test group was significantly longer than that of the control group (t = 2.327, P = 0.031), while the tourniquet use time and total hospitalization time showed no significant difference between 2 groups (P > 0.05). All the patients were followed up 6-8 months (mean, 7.2 months). Wound complications occurred in 3 cases (7.3%) of the control group and in 2 cases (10.5%) of the test group, showing no significant difference (χ2 = 0.175, P = 0.676). Color ultrasonography showed no pulmonary embolism and DVT at 6 weeks after TKA. There were significant differences in PT, TT, and FIB between at pre- and post-TKA in the same group, but no significant difference was found between 2 groups. The APTT and D-dimer had significant differences between at pre- and post-TKA in the same group, and between groups. There was no significant interaction effect between time and group for each index.. Preoperative abnormal D-dimer level should not be regarded as a contraindication for TKA. The risks of DVT and wound complications in patients with abnormal D-dimer level are similar to patients with normal D-dimer level using rivaroxaban administration after TKA. It is unnecessary to conventional monitor D-dimer and other coagulation and hemorrhage laboratory tests in the patients after TKA.

Topics: Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Factor Xa Inhibitors; Fibrin Fibrinogen Degradation Products; Humans; Knee Joint; Length of Stay; Morpholines; Osteoarthritis, Knee; Postoperative Complications; Postoperative Period; Preoperative Care; Prothrombin Time; Range of Motion, Articular; Rivaroxaban; Safety; Thiophenes; Venous Thrombosis

Topics: Administration, Oral; Anticoagulants; Chemoprevention; Costs and Cost Analysis; Humans; Morpholines; Orthopedic Procedures; Orthopedics; Outcome Assessment, Health Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Russia; Secondary Prevention; Thiophenes; Traumatology; Venous Thromboembolism

Rivaroxaban is the first licensed oral direct inhibitor of factor Xa. Recent studies from the RECORD trials suggest rivaroxaban has superior efficacy compared to enoxaparin in preventing venous thromboembolism (VTE) with no significant increase in the major bleeding risk. Concerns remain regarding the incidence of minor bleeding, consequent delayed wound healing and subsequent risk of infection. The aim of this observational study was to assess the incidence of post-operative complications in patients receiving either rivaroxaban or enoxaparin thromboprophylaxis following elective hip and knee arthroplasty.. A total of 258 patients undergoing elective total hip or knee arthroplasty within one NHS Trust were included. A total of 202 subjects (mean age, 70.7 years ± 10.0, 43 % men) received a daily dose of 10 mg of oral rivaroxaban and 56 (mean age, 70.9 years ± 9.8, 39 % men) had a daily subcutaneous injection of 40 mg of enoxaparin as thromboprophylaxis. Endpoints included VTE (deep vein thrombosis and pulmonary embolism), haemorrhagic wound complications, hospital re-admission, requirement for blood transfusion, minor and major bleeding and death.. There were no significant differences in the incidence of VTE, requirement for blood transfusion and readmission rate between rivaroxaban and enoxaparin-treated patients. The incidence of minor bleeding (2.0 vs. 0 %) and haemorrhagic wound complications (5.0 vs. 1.8 %) were non-significantly higher in the rivaroxaban-treated group. There were no cases of pulmonary embolism, major bleeding or death in either group.. Our experience with rivaroxaban in elective hip and knee arthroplasty showed no significant difference in the incidence of VTE or major bleeding. There was, however, a tendency to greater risk of minor bleeding and wound complications that were largely haemorrhagic in nature, which may have reached significance in a larger study.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Chemoprevention; Elective Surgical Procedures; Enoxaparin; Female; Hemorrhage; Humans; Male; Middle Aged; Morpholines; Osteoarthritis, Hip; Osteoarthritis, Knee; Outcome and Process Assessment, Health Care; Postoperative Complications; Rivaroxaban; Thiophenes; United Kingdom; Venous Thromboembolism; Wound Healing

Pulmonary embolism is a leading cause of fatality in elective orthopaedics. Recently introduced oral thromboprophylaxis (rivaroxaban) has a logistic advantage but has also raised early concerns amongst arthroplasty surgeons. The aim of this study was to evaluate the impact of rivaroxaban as a chemical thromboprophylaxis following knee arthroplasty in reference to radiologically diagnosed PE and return to theatre following wound complication.. Following the introduction of new NICE guidelines in our institute 266 consecutive TKR receiving rivaroxaban were studied prospectively and compared with retrospectively collected consecutive 596 TKR prior to adoption of the guidelines. Both of these groups were studied for radiologically diagnosed symptomatic VTE episodes within 90days and return to theatre following wound complication.. A total of 862 cases were studied, out of which 596 were in the retrospective control group and 266 were in the prospective rivaroxaban group. Both the groups had a female predominance with a mean age at the time of surgery as 68 and 69 in control and prospective cohort respectively. There were 24 radiologically diagnosed symptomatic PE and one DVT in the control group whereas, the rivaroxaban prospective group had 2 PE and 2 DVT cases. The return to theatre following wound complication was 2 and 7 in control and prospective group respectively.. Following the introduction of rivaroxaban the number of symptomatic radiologically confirmed PE events declined (p=0.0084) but the return to theatre rate due to wound complications increased (p=0.0049).. III.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Knee; Case-Control Studies; Female; Follow-Up Studies; Humans; Middle Aged; Morpholines; Postoperative Complications; Primary Prevention; Pulmonary Embolism; Retrospective Studies; Risk Assessment; Rivaroxaban; Survival Rate; Thiophenes; Time Factors; Treatment Outcome; Venous Thromboembolism

To compare the effects of rivaroxaban and enoxaparin on hidden blood loss after total hip arthroplasty (THA).. A retrospective analysis was made on the clinical data of 76 patients (93 hips) with avascular necrosis of the femoral head who underwent primary THA between June 2009 and January 2012. After operation, 10 mg rivaroxaban was used at 6-10 hours for 14 days in 44 cases (54 hips) (rivaroxaban group) and 4 000 U enoxaparin at 12 hours for 14 days in 32 cases (39 hips) (enoxaparin group). There was no significant difference in age, gender, weight, height, disease duration, grade of avascular necrosis of the femoral head, and lesion hips between 2 groups (P > 0.05). The total blood loss, dominant blood loss, hidden blood loss, and percentage of hidden blood loss were calculated according to the formula. The bleeding events were recorded within 35 days after operation.. The total blood loss was (1 509.56 +/- 325.23) mL; the dominant blood loss was (928.09 +/- 210.50) mL; the hidden blood loss was (581.47 +/- 215.01) mL; and the percentage of hidden blood loss was 37.88% +/- 10.42% in the rivaroxaban group. The total blood loss was (1 521.38 +/- 516.49) mL; the dominant blood loss was (917.50 +/- 378.73) mL, the hidden blood loss was (603.88 +/- 377.15) mL, and the percentage of hidden blood loss was 38.18% +/- 18.33% in the enoxaparin group. There was no significant difference in the above indicators between 2 groups (P > 0.05). The incidence of bleeding event was 9.1% (4/44) in the rivaroxaban group and was 3.1% (1/32) in the enoxaparin group, showing no significant difference (Chi2=1.073, P=0.390).. There is no significant difference in the risk of hidden blood loss and incidence of bleeding event for primary THA between the rivaroxaban and the enoxaparin use.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Blood Volume; Enoxaparin; Female; Femur Head Necrosis; Humans; Injections, Subcutaneous; Male; Middle Aged; Morpholines; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Rivaroxaban; Thiophenes; Young Adult

The use of novel oral anticoagulants (NOACs) is increasing since these drugs are at least as efficacious and safe as vitamin K antagonists (VKAs) for the management of patients with non-valvular atrial fibrillation and venous thromboembolism. Compared with VKAs, NOACs have a faster onset and offset of action, a predictable and consistent pharmacokinetic profile, fewer drug interactions, and ease of use since anticoagulant monitoring is not required. Current perioperative management will be affected by these characteristics, with the potential to obviate the need for heparin bridging. This review aims to summarize the current evidence of perioperative thromboembolic and bleeding risk during anticoagulant interruption, which is derived predominantly from patients receiving VKA therapy, and early studies involving NOACs which mainly focus on patients who are receiving dabigatran. The role of heparin bridging is discussed. We also provide a practical approach for the perioperative management of patients who are receiving NOAC therapy.

Topics: Aged; Antithrombins; Benzimidazoles; beta-Alanine; Dabigatran; Humans; Male; Morpholines; Perioperative Care; Postoperative Complications; Pyrazoles; Pyridones; Risk Assessment; Rivaroxaban; Thiophenes; Thromboembolism

Topics: Anticoagulants; Atrial Fibrillation; Benzimidazoles; Canada; Contraindications; Dabigatran; Drug Dosage Calculations; Drug Interactions; Humans; Morpholines; Postoperative Complications; Pyridines; Rivaroxaban; Stroke; Thiophenes; Venous Thromboembolism; Venous Thrombosis

This study assesses the use of new anticoagulants for the prevention of venous thromboembolism (VTE) in patients undergoing elective orthopedic surgery using traditional cost-effectiveness analysis and efficiency frontier methodology.. Efficiency frontier methodology has the potential to systematically improve the information used in policy and decision making, though it is still relatively uncommon in health economics. Anticoagulation in elective orthopedic surgery provides a fitting and timely case study for examining the influence of choosing one methodology over another.. An economic model was developed to capture the relative benefits and consequences of choosing one anticoagulation strategy over another in the context of orthopedic surgery. Three novel oral anticoagulants (apixaban, rivaroxaban, dabigatran) are compared with enoxaparin 40 mg daily from the UK National Health Service perspective using traditional cost-effectiveness estimates (cost/quality-adjusted life years, cost/life years gained) and the efficiency frontier. The latter explicitly includes embolic and bleeding events as outcomes. A 5-year time horizon was adopted.. Total discounted costs ranged from about £200 000 to £431 000 over 5 years per 1000 patients undergoing elective total hip arthroplasty, and from £243 000 to £463 000 per 1000 patients for elective total knee arthroplasty. Analysis of the efficiency frontier demonstrates that apixaban and rivaroxaban are the preferred choices, depending on the outcome examined and the type of surgery. In terms of safety, apixaban is associated with more bleeding events avoided; yet, rivaroxaban demonstrated better VTE outcomes.. Traditional cost-effectiveness analysis systematically excludes information related to the safety profiles of these anticoagulants. The efficiency frontier approach presented in this study provides critical information, without substantial effort, to permit a fully informed decision by taking into account all relevant outcomes as they relate to the costs associated with treatment choice.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement; Benzimidazoles; beta-Alanine; Cost-Benefit Analysis; Dabigatran; Decision Trees; Drug Costs; Elective Surgical Procedures; Enoxaparin; Female; Humans; Male; Markov Chains; Models, Economic; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Quality-Adjusted Life Years; Rivaroxaban; State Medicine; Thiophenes; United Kingdom; Venous Thromboembolism

Topics: Anticoagulants; Benzimidazoles; beta-Alanine; Blood Coagulation Disorders; Clinical Trials as Topic; Dabigatran; Humans; Morpholines; Postoperative Complications; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Thiophenes; Warfarin

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Humans; Morpholines; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes

A cost-effectiveness model for rivaroxaban evaluated the cost-effectiveness of prophylaxis with rivaroxaban (a once-daily, orally administered Factor Xa inhibitor) vs enoxaparin in the prevention of venous thromboembolism (VTE) after total hip replacement (THR) and total knee replacement (TKR). This Canadian analysis was conducted using the Ontario Ministry of Health perspective over a 5-year time horizon. The model combined clinical data and builds upon existing economic models.. The model included both acute VTE (represented as a decision tree) and long-term complications (represented as a Markov process with 1-year cycles) phases. The model allowed VTE event rates, quality-adjusted life expectancy and direct medical costs to be estimated over a 5-year time horizon, based on current approved practice patterns in Canada. A number of one-way sensitivity analyses were performed on the baseline assumptions, including a comparison of rivaroxaban with dalteparin, and probabilistic sensitivity analyses were performed to address any uncertainty concerning model inputs.. When comparing equal durations of therapy, rivaroxaban dominated enoxaparin in the prevention of VTE events in patients undergoing THR and TKR, providing more benefit at a lower cost. Rivaroxaban was cost-effective when comparing 35 days' prophylaxis with 14 days' prophylaxis with enoxaparin following THR. One-way and probabilistic sensitivity analyses demonstrated that the results of the economic analysis were robust to variations in key inputs. Rivaroxaban remained dominant during one-way sensitivity analyses comparing rivaroxaban with dalteparin after THR or TKR.. Although clinical trial data were used in the prophylaxis module, assumptions and values used in the post-prophylaxis and long-term complication (LTC) modules were based on several different literature sources; it was not always possible to source Canadian data.. This economic analysis suggests that the use of rivaroxaban for the prophylaxis of VTE after THR or TKR in Canada was cost-effective.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Cost-Benefit Analysis; Humans; Morpholines; Ontario; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Interactions; Humans; Morpholines; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Aged; Anesthesia, Conduction; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Drug Administration Schedule; Female; Hip Prosthesis; Humans; Morpholines; Obesity; Postoperative Complications; Postoperative Hemorrhage; Practice Guidelines as Topic; Premedication; Prosthesis Failure; Recurrence; Reoperation; Risk; Risk Factors; Rivaroxaban; Stockings, Compression; Thiophenes; Venous Thromboembolism

Patients undergoing major orthopedic surgery, including total hip arthroplasty (THA) and total knee arthroplasty (TKA), are at high risk for developing venous thromboembolism (VTE). Although largely a preventable complication, VTE develops in a significant proportion of patients, highlighting the need for improved methods of VTE prevention. Current thromboprophylactic options are limited by unpredictable pharmacokinetics and pharmacodynamics (vitamin K antagonists), parenteral/subcutaneous administration (heparin and low-molecular-weight heparins), complicated dosing, and increased risk of bleeding.Rivaroxaban is an oral, direct Factor Xa inhibitor that has recently received marketing authorization in the United States for prophylaxis of deep vein thrombosis in patients undergoing hip or knee replacement surgery. The clinical pharmacology of rivaroxaban supports a convenient, oral, once-daily dosing regimen without the need for routine coagulation monitoring after THA or TKA. A comprehensive phase II and III study program supports its safety and efficacy for VTE prevention after THA or TKA. Phase III results have demonstrated the superior efficacy of rivaroxaban regimens compared with enoxaparin regimens, with similar rates of major bleeding. This article provides an overview of the phase II and III results that support the use of this agent for the prevention of VTE after elective total hip or knee replacement.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Patients undergoing major orthopaedic surgery (MOS), such as total hip (THR) or total knee replacement (TKR), are at high risk of developing venous thromboembolism (VTE). For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG) system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI) and the German hospital perspective.. To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI) perspective and to analyse financial incentives from the German hospital perspective.. Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR) and two perspectives (SHI and hospital) per setting.. Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR) compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated). However, the cost-effectiveness after THR (€17.8 cost per person) remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR) and €31.8 (THR) per case respectively.. Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cost-Benefit Analysis; Databases, Factual; Decision Trees; Enoxaparin; Germany; Humans; Morpholines; Multicenter Studies as Topic; National Health Programs; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

The oral anticoagulant rivaroxaban is recommended for venous thromboembolic prophylaxis following lower limb arthroplasty. Concerns regarding high rates of wound complications following its use have prompted this multicenter comparison with low-molecular-weight heparins.. English hospital trusts that replaced a low-molecular-weight heparin with rivaroxaban for thromboprophylaxis in lower limb arthroplasty during 2009 were identified. Prospectively collected national data for these units were analyzed to determine the thirty-day rates of wound complications and major bleeding (cerebrovascular event or gastrointestinal hemorrhage) and the ninety-day rates of symptomatic deep venous thrombosis (proximal or distal), symptomatic pulmonary embolism, and all-cause inpatient mortality before and after the change to rivaroxaban. A total of 2762 patients prescribed rivaroxaban following knee or hip arthroplasty were compared with 10,361 patients prescribed a low- molecular weight heparin. Data were analyzed with use of odds ratios (ORs).. There were significantly fewer wound complications in the low-molecular-weight heparin group (2.81% compared with 3.85%; OR = 0.72, 95% confidence interval [CI] = 0.58 to 0.90; p = 0.005). There were no significant differences between the low-molecular-weight heparin and rivaroxaban groups in the rates of pulmonary embolism (0.55% compared with 0.36%; OR = 1.52, 95% CI = 0.78 to 2.98), major bleeding (OR = 0.73, 95% CI = 0.48 to 1.12), or all-cause mortality (OR = 0.93, 95% CI = 0.46 to 1.89). There were significantly more symptomatic deep venous thromboses in the low-molecular-weight heparin group (0.91% compared with 0.36%; OR = 2.51, 95% CI = 1.31 to 4.84; p = 0.004).. The rivaroxaban group had a higher wound complication rate and a lower deep venous thrombosis rate; there were no differences in symptomatic pulmonary embolism or all-cause mortality. Longer follow-up is needed to assess any potential relationship between wound complications and joint stiffness, latent infection, and limb consequences of deep venous thrombosis.

Topics: Age Distribution; Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Cerebral Hemorrhage; Cohort Studies; Confidence Intervals; Databases, Factual; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Middle Aged; Morpholines; Odds Ratio; Postoperative Complications; Retrospective Studies; Risk Assessment; Rivaroxaban; Sex Distribution; Surgical Wound Infection; Survival Analysis; Thiophenes; Treatment Outcome; Venous Thrombosis; Wound Healing

Post-operative complications after total hip or knee replacement can delay recovery, prolong hospitalisation, increase rates of re-admission and, in the most severe cases, lead to long-term disability or even death. In this analysis of pooled data from four large, randomised, phase III clinical trials that compared the oral, direct Factor Xa inhibitor rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement (n = 12,729), the incidence of complications, including bleeding and adverse events related to surgery (such as wound infection, wound dehiscence and haemarthrosis) are reported. Interventions and procedures relating to surgery are also compared between the groups. Bleeding events, including excessive wound haematoma and surgical-site bleeding, occurred at similar rates in the rivaroxaban and enoxaparin groups. Over the total study duration, adverse surgical events occurred at a similar rate in the rivaroxaban group compared with the enoxaparin group after total knee replacement (2.26% vs. 2.69%, respectively) and total hip replacement (1.48% vs. 1.65%, respectively). Blood loss, wound drainage and transfusion requirements were also similar between the two groups. This analysis shows that the incidence of adverse surgical events with rivaroxaban was similar to enoxaparin.

Topics: Anticoagulants; Arthroplasty, Replacement, Ankle; Arthroplasty, Replacement, Knee; Clinical Trials, Phase III as Topic; Enoxaparin; Hemarthrosis; Hemorrhage; Humans; Morpholines; Postoperative Complications; Randomized Controlled Trials as Topic; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

To analyze the impact of ivaroxaban on hidden blood loss and blood transfusion rate after primary total knee arthroplasty (TKA) by comparing with the use of low molecular weight heparin.. Between December 2009 and January 2011, the clinical data from 90 patients undergoing primary TKA were retrospectively analyzed. At 12 hours after operation, 45 patients were given ivaroxaban (10 mg/d) in the trial group and low molecular weight heparin injection (0.4 mL/d) in the control group for 14 days, respectively. There was no significant difference in gender, age, disease duration, or range of motion between 2 groups (P > 0.05).. The operation time was (92.32 +/- 23.13) minutes in the trial group and (89.81 +/- 18.65) minutes in the control group, showing no significant difference (t=0.26, P=0.79). The hidden blood loss was (40.18 +/- 14.85) g/L in the trial group and (34.04 +/- 12.96) g/L in the control group, showing significant difference (t=2.09, P=0.00); the dominant blood loss was (30.60 +/- 2.89) g/L and (28.85 +/- 8.10) g/L respectively, showing no significant difference (t=1.37, P=0.17). The blood transfusion rate was 73.33% (33/45) in the trial group and 55.56% (25/45) in the control group, showing no sigificant difference (chi2=3.10, P=0.08); the transfusion volume was (1.44 +/- 1.09) U and (1.06 +/- 1.17) U respectively, showing no significant difference (t=1.58, P=0.11). Stress ulcer occurred in 1 case of the trial group; symptomatic deep vein thrombosis of lower extremity and asymptomatic muscular venous thrombosis developed in 1 case and 4 cases of the control group respectively.. Ivaroxaban has effect on the hidden blood loss after primary TKA, which may increase postoperative blood loss and blood transfusion rate. The changes in hemoglobin should be monitored during the anticoagulant therapy, and the blood volume should be added promptly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Knee; Blood Transfusion; Female; Hemoglobins; Heparin, Low-Molecular-Weight; Humans; Male; Middle Aged; Morpholines; Osteoarthritis, Knee; Postoperative Complications; Postoperative Hemorrhage; Range of Motion, Articular; Retrospective Studies; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thrombosis

Rivaroxaban has been recommended for routine use as a thromboprophylactic agent in patients undergoing lower-limb arthroplasty. However, trials supporting its use have not fully evaluated the risks of wound complications. This study of 1048 total hip/knee replacements records the rates of return to theatre and infection before and after the change from a low molecular weight heparin (tinzaparin) to rivaroxaban as the agent of chemical thromboprophylaxis in patients undergoing lower-limb arthroplasty. During a period of 13 months, 489 consecutive patients undergoing lower-limb arthroplasty received tinzaparin and the next 559 consecutive patients received rivaroxaban as thromboprophylaxis. Nine patients in the control (tinzaparin) group (1.8%, 95% confidence interval 0.9 to 3.5) returned to theatre with wound complications within 30 days, compared with 22 patients in the rivaroxaban group (3.94%, 95% confidence interval 2.6 to 5.9). This increase was statistically significant (p = 0.046). The proportion of patients who returned to theatre and became infected remained similar (p = 0.10). Our study demonstrates the need for further randomised controlled clinical trials to be conducted to assess the safety and efficacy of rivaroxaban in clinical practice, focusing on the surgical complications as well as the potential prevention of venous thromboembolism.

Topics: Adult; Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Female; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Hip Prosthesis; Humans; Knee Prosthesis; Male; Middle Aged; Morpholines; Postoperative Care; Postoperative Complications; Prosthesis-Related Infections; Reoperation; Retrospective Studies; Rivaroxaban; Thiophenes; Thromboembolism; Tinzaparin

To compare the efficacy, in the prevention of venous thromboembolism (VTE), and safety, of rivaroxaban and dabigatran relative to the common comparator enoxaparin.. Two randomized clinical trials of dabigatran, one after total hip replacement (THR), RE-NOVATE, and one after total knee replacement (TKR), RE-MODEL, were identified as using the same enoxaparin regimen (40 mg once daily given the evening before surgery) and being of comparable duration to two rivaroxaban trials, RECORD1 and RECORD3. Indirect comparisons were performed on both efficacy and safety endpoints. To enable comparisons, symptomatic VTE results were based on the total study duration period, i.e. including the follow-up period. Major bleeding included surgical-site bleeding events.. After THR, rivaroxaban 10 mg once daily significantly reduced total VTE and symptomatic VTE relative to dabigatran 220 mg once daily (relative risk 0.34 and 0.19, respectively). After TKR, rivaroxaban significantly reduced total VTE versus dabigatran (relative risk 0.53); symptomatic VTE was not different between dabigatran and rivaroxaban. There was no significant difference in the rates of major bleeding for patients receiving rivaroxaban or dabigatran.. Based on the indirect comparisons, rivaroxaban was estimated to be more efficacious than dabigatran in the prevention of total VTE after THR and TKR. Our analysis relied upon published data for dabigatran and did not have the advantages of more detailed comparative data obtained directly from a randomized trial, as was the case with rivaroxaban. Further comparative research may be of value, but until available our conclusions represent the best available evidence.

Topics: Aged; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Dabigatran; Enoxaparin; Female; Health Care Costs; Humans; Male; Middle Aged; Morpholines; Postoperative Complications; Risk; Risk Factors; Rivaroxaban; Thiophenes; Venous Thromboembolism

It was the objective of this study to quantify the effects of rivaroxaban administration on global coagulation parameters associated with routine clinical procedures, we collected plasma samples from patients undergoing major orthopaedic surgery receiving rivaroxaban at various time points after drug administration. Forty-seven patients received rivaroxaban (10 mg daily) for venous thromboembolism prophylaxis. Blood samples were collected at four different time points: A) before surgery; B) before drug administration at day 4-5 after surgery (steady state of rivaroxaban); C) 2 hours (h) after drug administration and D) 12 h after drug administration. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), antithrombin (AT) level, fibrinogen level by Clauss method (FibC), and derived fibrinogen (dFIB) level were assessed with various reagents. At 2 h after rivaroxaban administration, the PT and aPTT clotting times were significantly prolonged to different extents up to 1.4 fold, whereas 12 h after drug administration, no significant effect was observed. Rivaroxaban administration had no influence on the TT or the FibC concentration. The dFIB assay was differentially affected by rivaroxaban when different reagents were tested. The AT assay dependent on thrombin activity was not influenced by rivaroxaban, whereas the AT levels dependent on factor Xa activity were significantly increased by rivaroxaban. Clinicians should be aware of the time-dependent influence of rivaroxaban on factor Xa-dependent routine coagulation assays. Therefore, routine coagulation parameters should be assessed directly before drug administration to keep the interaction of rivaroxaban low.

Topics: Aged; Anticoagulants; Antithrombins; Blood Coagulation; Blood Coagulation Tests; Clinical Protocols; Drug Interactions; Factor Xa Inhibitors; Female; Fibrinogen; Humans; Male; Middle Aged; Morpholines; Orthopedic Procedures; Postoperative Complications; Rivaroxaban; Thiophenes; Time Factors; Venous Thromboembolism

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Embolism; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Thrombosis

Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the lack of any specific antidote in many instances. Their oral administration, without the need for dose adjustment, and without requirement for a laboratory monitoring will increase their use in a large number of patients, in those indications for which an approval has been granted by health authorities.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; beta-Alanine; Contraindications; Dabigatran; Drug Approval; Humans; Kidney; Liver; Morpholines; Postoperative Complications; Pulmonary Embolism; Pyrazoles; Pyridones; Rivaroxaban; Thiophenes; Thromboembolism; United States; United States Food and Drug Administration

Extended thromboprophylaxis is vital in patients undergoing total hip arthroplasty (THA) because of the prolonged risk of venous thromboembolism (VTE). Despite evidence that extended prophylaxis can reduce the incidence of symptomatic VTE in this high-risk patient population and the evidence-based guideline recommendations, a large proportion of patients still do not receive an adequate duration of thromboprophylaxis. This is partly due to the limitations of conventional anticoagulants, such as the subcutaneous route of administration or the requirement for routine coagulation monitoring and dose adjustment. New oral anticoagulants (such as the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitor rivaroxaban) could address the current unmet need. Phase III clinical studies in VTE prevention in patients undergoing THA and total knee arthroplasty (TKA) showed that dabigatran etexilate was non-inferior to the EU regimen of enoxaparin, but did not achieve non-inferiority to the US regimen of enoxaparin. In contrast, rivaroxaban demonstrated superiority to both enoxaparin regimens for the prevention of VTE after THA and TKA, without a significant increase in major bleeding rates. Their convenient, once-daily, fixed dosing, with no need for routine coagulation monitoring, could facilitate adherence to evidence-based guideline recommendations of extended thromboprophylaxis after THA.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Benzimidazoles; Dabigatran; Elective Surgical Procedures; Humans; Morpholines; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Venous thromboembolism (VTE) is a common, sometimes even fatal though preventable complication after surgical interventions, especially in orthopaedic surgery. The risk can be reduced by more than 50 % by mechanical means and different anticoagulant drugs. However, only few patients receive adequate treatment. Medicamentous options are limited and somewhat difficult. Most anticoagulant substances act indirectly, therefore their efficacy can easily be impaired. For some, the pharmacokinetics are quite unfavourable. Furthermore, these drugs can cause severe adverse reactions; and since drug therapy either needs daily injections or routine blood checks, its acceptance is limited even further. Fortunately, new substances have reached phase III and will shortly be released. They have a broad therapeutic index, favourable pharmacodynamics and -kinetics and seem to cause only few adverse events. Rivaroxaban, for example, is approved for orthopaedic interventions like total hip or knee replacement. Orally administered, it interacts directly with factor Xa. It proved to be superior compared to the standard therapy with Enoxaparin, has a similar risk profile and needs no routine blood checks. The following article gives a critical survey of the problem, therapeutic options, current guidelines and new possibilities. Hopefully, these new simplified therapy options will increase the acceptance of VTE prophylaxis so that the rate of fatal complications after orthopaedic interventions can further be reduced.

Topics: Administration, Oral; Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Coagulation Tests; Combined Modality Therapy; Drug Approval; Drug Interactions; Early Ambulation; Enoxaparin; Factor Xa Inhibitors; Humans; Intermittent Pneumatic Compression Devices; Morpholines; Orthopedic Procedures; Postoperative Care; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Stockings, Compression; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Fibrinolytic Agents; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Practice Guidelines as Topic; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Antithrombins; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Clinical Trials as Topic; Cost-Benefit Analysis; Dabigatran; Enoxaparin; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Models, Economic; Morpholines; Polysaccharides; Postoperative Complications; Pyridines; Quality-Adjusted Life Years; Rivaroxaban; Thiophenes; Treatment Outcome; Venous Thromboembolism

Topics: Administration, Oral; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Biological Availability; Dose-Response Relationship, Drug; Drug Interactions; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; International Normalized Ratio; Metabolic Clearance Rate; Morpholines; Partial Thromboplastin Time; Postoperative Complications; Protein Binding; Prothrombin Time; Rivaroxaban; Thiophenes; Thromboembolism

Topics: Arthroplasty, Replacement, Hip; Drug Administration Schedule; Fibrinolytic Agents; Humans; Morpholines; Postoperative Care; Postoperative Complications; Retrospective Studies; Rivaroxaban; Thiophenes; Venous Thromboembolism

During the past five decades, anticoagulant therapy has consisted of rapidly acting parenteral drugs (unfractionated heparin [UFH] low-molecular-weight heparins [LMWH]) for prevention of venous thromboembolism and initial treatment of arterial and venous thromboembolism, whereas vitamin K antagonists (VKA) are used for longer term oral treatment. These drugs act by indirectly inhibiting several activated plasma clotting factors (UFH, LMWH) or by blocking the synthesis of some of them (VKA). In recent years, compounds that specifically block activated coagulation factor X (FXa) or thrombin have been developed. Thus, fondaparinux, and its long-acting derivative idraparinux, are administered subcutaneously. These substances inhibit F Xa indirectly via antithrombin. Small molecules have also been developed that directly block FXa (rivaroxaban, apixaban) or thrombin (dabigatran etexilate) following oral administration. In the present review we discuss the currently available evidence supporting the use of these new anticoagulants, in particular rivaroxaban and dabigatran etexilate, in the setting of thromboprophylaxis following major orthopaedic surgery, and the broader perspectives that these new drugs may open up in the next few years.

Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Benzimidazoles; Dabigatran; Heparin; Heparin, Low-Molecular-Weight; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Thromboembolism; Thrombolytic Therapy; Vitamin K

Topics: Humans; Morpholines; Orthopedics; Postoperative Complications; Premedication; Rivaroxaban; Thiophenes; Thrombosis; Treatment Outcome

Topics: Anticoagulants; Benzimidazoles; Dabigatran; Enoxaparin; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pyridines; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Anticoagulants; Clinical Trials as Topic; Enoxaparin; Factor Xa Inhibitors; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Venous Thromboembolism

Topics: Fibrinolytic Agents; Humans; Morpholines; Postoperative Complications; Rivaroxaban; Thiophenes; Thromboembolism

New oral anticoagulants, soon available in clinical practice, will deeply change the management of venous thromboembolism. The main advantage of these drugs is the route of administration. Moreover, among the new oral anticoagulants, rivaroxaban has a better efficacy than enoxaparin to prevent thromboembolic events after major orthopaedic surgery (THR and TKR). In phase III studies, safety profile seems adequate. A new era for prophylaxis of VTE is beginning with the new oral anticoagulants. However, improvement in the management of patients with renal failure, obese patients or elderly is needed considering that these patients have a high thrombotic and/or hemorrhagic risk.

Topics: Administration, Oral; Aged; Anticoagulants; Clinical Trials, Phase III as Topic; Comorbidity; Enoxaparin; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Kidney Failure, Chronic; Morpholines; Obesity; Postoperative Complications; Preanesthetic Medication; Rivaroxaban; Thiophenes; Thromboembolism; Thrombophilia; Venous Thrombosis