Explore the vast range of titles available.

Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty; oral regimens could enable shorter hospital stays. We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty. In a randomised, double-blind, phase III study, 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily, beginning 6–8 h after surgery, or subcutaneous enoxaparin 30 mg every 12 h, starting 12–24 h after surgery. Patients had mandatory bilateral venography between days 11 and 15. The primary efficacy outcome was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism, or death from any cause up to day 17 after surgery. Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per-protocol population (absolute non-inferiority limit −4%); if non-inferiority was shown, we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population. The primary safety outcome was major bleeding. This trial is registered with ClinicalTrials.gov, number NCT00362232. The primary efficacy outcome occurred in 67 (6·9%) of 965 patients given rivaroxaban and in 97 (10·1%) of 959 given enoxaparin (absolute risk reduction 3·19%, 95% CI 0·71–5·67; p=0·0118). Ten (0·7%) of 1526 patients given rivaroxaban and four (0·3%) of 1508 given enoxaparin had major bleeding (p=0·1096). Oral rivaroxaban 10 mg once daily for 10–14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty. Bayer Schering Pharma AG, Johnson & Johnson Pharmaceutical Research & Development.

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 A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; p noninferiority  < 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 were 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. Trial registration EINSTEIN-PE: ClinicalTrials.gov, NCT00439777 ; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193 .

Chronic thromboembolic pulmonary hypertension is believed to be rare after an episode of acute pulmonary embolism. This study showed that the incidence of this serious complication was nearly 4 percent — substantially higher than previously reported — and was associated with previous pulmonary embolism, large perfusion defects, and an idiopathic presentation. Possible approaches to prevention are discussed. The incidence of this serious complication was nearly 4 percent. Chronic pulmonary hypertension is considered a relatively rare complication of pulmonary embolism but is associated with considerable morbidity and mortality. 1 – 3 It is commonly believed that symptoms become manifest only several years after the initial episode of pulmonary embolism. However, the true frequency (estimated at 0.1 percent among patients who survive a pulmonary embolism) and timing are not well established, and there is limited documentation concerning predisposing factors that could be addressed in an effort to prevent this feared complication. It has been hypothesized that in situ thrombosis and pulmonary arteriopathy are common causes of vascular occlusion leading to chronic . . .

In this study involving nearly 3400 patients with venous thromboembolism, both prophylactic and therapeutic doses of rivaroxaban were superior to aspirin in reducing the risk of recurrent thromboembolism with a similar risk of bleeding. Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke. 1 – 3 The mainstay of treatment is anticoagulation, 4 and in patients without active cancer, guidelines suggest the use of direct oral anticoagulant agents such as rivaroxaban over vitamin K antagonists such as warfarin. 4 Anticoagulation therapy is administered for 3 months or longer, depending on the balance between the risk of recurrent venous thromboembolism and the risk of bleeding. 4 In patients without reversible risk factors, the risk of recurrent venous thromboembolism is as much as 10% in the first . . .

In the treatment of patients with acute pulmonary embolism, the efficacy of rivaroxaban, a factor Xa inhibitor, was similar to that of traditional anticoagulation therapy. There was less bleeding in the group receiving rivaroxaban, which supports its use in the treatment of this condition. Pulmonary embolism is a common disease, with an estimated annual incidence of 70 cases per 100,000 population. 1 , 2 The condition usually leads to hospitalization and may recur; it can be fatal. 3 For half a century, the standard therapy for most patients with pulmonary embolism has been the administration of heparin, overlapped and followed by a vitamin K antagonist. 4 , 5 This regimen is effective but complex. 5 – 9 Recently developed oral anticoagulants that are directed against factor Xa or thrombin overcome some limitations of standard therapy, including the need for injection and for regular dose adjustments on the basis of laboratory monitoring. . . .

In this clinical trial, rivaroxaban, an oral factor Xa inhibitor, was effective in the initial and continued treatment of symptomatic venous thromboembolism; it may become part of the treatment armamentarium for this common clinical problem. Acute venous thromboembolism (i.e., deep-vein thrombosis [DVT] or pulmonary embolism) is a common disorder with an annual incidence of approximately 1 or 2 cases per 1000 persons in the general population. 1 , 2 Short-term treatment is effective, with the risk of recurrent disease — the major complication — reduced from an estimated 25% to about 3% during the first 6 to 12 months of therapy. 3 The risk of recurrence remains after treatment ends and can reach 5 to 10% during the first year. 4 , 5 Standard treatment for acute venous thromboembolism is limited by the need for parenteral heparin initially, with overlapping . . .

Objective To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. Design Double blind randomised placebo controlled trial. Setting 35 centres in eight countries. Participants 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. Interventions 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days. Outcome measure The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. Results 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. Conclusion Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

Much attention has been paid in recent years to optimizing the diagnosis of acute pulmonary embolism (PE). However, little is known about the changes in clot burden that occur at the level of the pulmonary arteries after documented PE. It is often problematic to distinguish between a new or residual defect on lung scintigraphy or helical CT. This may lead to falsely labeling patients with residual PE as having recurrent PE and consequent unnecessary treatment changes. We performed a systematic analysis of studies of imaging tests (radionuclide and CT) evaluating resolution rate of PE with independent assessment of predefined methodologic criteria by two investigators. We identified 29 clinical studies. Of these, 25 studies were excluded and 4 studies were included in our review. Because studies differed largely in patient selection, duration of anticoagulation, and timing of follow-up, the studies were not pooled but briefly described. The percentage of patients with residual pulmonary thrombi was 87% at 8 days after diagnosis, 68% after 6 weeks, 65% after 3 months, 57% after 6 months, and 52% after 11 months. This review shows that complete resolution of PE is not routinely achieved between 8 days and 11 months after diagnosis. More than 50% of patients with PE still have defects 6 months after diagnosis, after which resolution of thrombi appears to reach a plateau phase. Physicians should be aware of the high percentage of incomplete resolution of pulmonary emboli. Routine re-imaging after cessation of anticoagulant therapy in patients with PE to obtain a new baseline could be considered.

The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. Randomized, double-blind study. 154 centers worldwide. 2205 patients with acute symptomatic deep venous thrombosis. Fondaparinux, 7.5 mg (5.0 mg in patients weighing <50 kg and 10.0 mg in patients weighing >100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% CI, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosis.

Warfarin is used for prophylaxis of venous thromboembolism in patients undergoing total knee arthroplasty. However, it is associated with rates of deep venous thrombosis (DVT) of approximately 38% to 55% and requires routine coagulation monitoring and frequent dose adjustment. Ximelagatran, an oral direct thrombin inhibitor, has shown promising efficacy and tolerability in patients undergoing total hip or knee arthroplasty. To compare the efficacy and safety of ximelagatran and warfarin for prophylaxis of venous thromboembolism after total knee arthroplasty. Randomized, double-blind, parallel-group trial. 74 North American hospitals. 680 patients who had undergone total knee arthroplasty. 7 to 12 days of treatment with oral ximelagatran, 24 mg twice daily, starting on the morning after surgery, or warfarin (target international normalized ratio, 2.5 [range, 1.8 to 3.0]), starting on the evening of the day of surgery. Principal end points were asymptomatic DVT on mandatory venography; symptomatic DVT confirmed by ultrasonography or venography; symptomatic, objectively proven pulmonary embolism; and bleeding. All were assessed by blinded adjudication locally and at a central study laboratory. On central adjudication, incidence of venous thromboembolism was 19.2% (53 of 276 patients) in the ximelagatran group and 25.7% (67 of 261 patients) in the warfarin group (difference, -6.5 percentage points [95% CI, -13.5 to 0.6 percentage points]; P = 0.070). On local assessment, incidence was 25.4% in the ximelagatran group and 33.5% in the warfarin group (P = 0.043). In the ximelagatran and warfarin groups, respectively, major bleeding occurred in 1.7% and 0.9% of patients and minor bleeding occurred in 7.8% and 6.4% of patients. No variables related to bleeding differed significantly between the two groups. For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.