Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism : a pooled analysis of the EINSTEIN-DVT and PE randomized studies

Background: Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods: A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results: 8282 patients were enrolled. 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 rivaroxaban-treated patients (2.1%) compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66-1.19; pnoninferiority<0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37-0.79; p=0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban was similar compared with standard-therapy. Conclusion: The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups

Removing noise from pyrosequenced amplicons

Background In many environmental genomics applications a homologous region of DNA from a diverse sample is first amplified by PCR and then sequenced. The next generation sequencing technology, 454 pyrosequencing, has allowed much larger read numbers from PCR amplicons than ever before. This has revolutionised the study of microbial diversity as it is now possible to sequence a substantial fraction of the 16S rRNA genes in a community. However, there is a growing realisation that because of the large read numbers and the lack of consensus sequences it is vital to distinguish noise from true sequence diversity in this data. Otherwise this leads to inflated estimates of the number of types or operational taxonomic units (OTUs) present. Three sources of error are important: sequencing error, PCR single base substitutions and PCR chimeras. We present AmpliconNoise, a development of the PyroNoise algorithm that is capable of separately removing 454 sequencing errors and PCR single base errors. We also introduce a novel chimera removal program, Perseus, that exploits the sequence abundances associated with pyrosequencing data. We use data sets where samples of known diversity have been amplified and sequenced to quantify the effect of each of the sources of error on OTU inflation and to validate these algorithms

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Fondaparinux for the treatment of superficial vein thrombosis in the legs

Producción CientíficaThe efficacy and safety of anticoagulant treatment for patients with acute, symptom- atic superf icial-vein thrombosis in the legs, but without concomitant deep-vein thrombosis or symptomatic pulmonary embolism at presentation, have not been es- tablished. Methods In a randomized, double-blind trial, we assigned 3002 patients to receive either fonda- parinux, administered subcutaneously at a dose of 2.5 mg once daily, or placebo for 45 days. The primary eff icacy outcome was a composite of death from any cause or symptomatic pulmonary embolism, symptomatic deep-vein thrombosis, or symp- tomatic extension to the saphenofemoral junction or symptomatic recurrence of superf icial-vein thrombosis at day 47. The main safety outcome was major bleeding. The patients were followed until day 77. Results The primary eff icacy outcome occurred in 13 of 1502 patients (0.9%) in the fonda- parinux group and 88 of 1500 patients (5.9%) in the placebo group (relative risk reduction with fondaparinux, 85%; 95% conf idence interval [CI], 74 to 92; P<0.001). The incidence of each component of the primary efficacy outcome was significantly reduced in the fondaparinux group as compared with the placebo group, except for the outcome of death (0.1% in both groups). The rate of pulmonary embolism or deep-vein thrombosis was 85% lower in the fondaparinux group than in the pla- cebo group (0.2% vs. 1.3%; 95% CI, 50 to 95; P<0.001). Similar risk reductions were observed at day 77. A total of 88 patients would need to be treated to prevent one instance of pulmonary embolism or deep-vein thrombosis. Major bleeding occurred in one patient in each group. The incidence of serious adverse events was 0.7% with fondaparinux and 1.1% with placebo. Conclusions Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treat- ment of patients with acute, symptomatic superf icial-vein thrombosis of the legs and did not have serious side effects. (Funded by GlaxoSmithKline; ClinicalTrials .gov number, NCT00443053.

Open Pulmonary Thromboembolectomy in Patients with Major Pulmonary Thromboembolism

PURPOSE: We retrospectively analyzed open pulmonary thromboembolectomy in patients with acute and chronic pulmonary thromboembolism. MATERIALS AND METHODS: Between August 1990 and May 2005, 12 consecutive patients with acute and chronic pulmonary thromboembolism underwent open pulmonary thromboembolectomy at Yonsei Cardiovascular Center. Their mean age was 47.5 years, and 7 of the patients were female. Among 12 patients, 5 had acute onset, and 7 had chronic disease, and 9 patients were associated with deep venous thrombosis. Extent of pulmonary embolism was massive in 3 patients with hemodynamic instability, and submassive in 8 patients. Preoperative echocardiogram revealed elevated right ventricular pressure in all patients, and 7 patients were in NYHA functional class III or IV. Pulmonary thromboembolectomy was performed in all patients under total circulatory arrest. RESULTS: There were 2 hospital deaths (16.7%). Among the patients who survived, mean right ventricular pressure was decreased significantly from 64.3mmHg to 34.0mmHg with improvement of NYHA functional class. CONCLUSION: Open pulmonary thromboembolectomy is thought to be an immediate and definitive treatment for massive pulmonary embolism with optimal results. Even though operative mortality is still high, early diagnosis and immediate surgical intervention in highly selective patients may improve the clinical outcomeope

Rivaroxaban or aspirin for extended treatment of venous thromboembolism

Background: Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. Methods: In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. Results: A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P&lt;0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups. Conclusions: Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates.</p

Rivaroxaban or Aspirin for extended treatment of venous thromboembolism

Background: although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin. Methods: in this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding. Results: a total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups. Conclusions: among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439)

Complications related to deep venous thrombosis prophylaxis in trauma: a systematic review of the literature

Deep venous thrombosis prophylaxis is essential to the appropriate management of multisystem trauma patients. Without thromboprophylaxis, the rate of venous thrombosis and subsequent pulmonary embolism is substantial. Three prophylactic modalities are common: pharmacologic anticoagulation, mechanical compression devices, and inferior vena cava filtration. A systematic review was completed using PRISMA guidelines to evaluate the potential complications of DVT prophylactic options. Level one evidence currently supports the use of low molecular weight heparins for thromboprophylaxis in the trauma patient. Unfortunately, multiple techniques are not infrequently required for complex multisystem trauma patients. Each modality has potential complications. The risks of heparin include bleeding and heparin induced thrombocytopenia. Mechanical compression devices can result in local soft tissue injury, bleeding and patient non-compliance. Inferior vena cava filters migrate, cause inferior vena cava occlusion, and penetrate the vessel wall. While the use of these techniques can be life saving, they must be appropriately utilized