Explore the vast range of titles available.

In this multicenter trial, the oral factor Xa inhibitor apixaban was compared with enoxaparin and warfarin for the treatment of acute venous thromboembolism. Apixaban was noninferior to enoxaparin and warfarin with respect to efficacy and superior with respect to safety. Venous thromboembolism, with an annual incidence of 1 to 2 cases per 1000 persons in the general population, is the third most common cause of vascular death after myocardial infarction and stroke. 1 Conventional treatment consists of a parenteral anticoagulant, such as enoxaparin, for at least 5 days, and warfarin begun during this time and continued for at least 3 months. 2 Although effective, this regimen presents a challenge because enoxaparin requires daily subcutaneous injections, and warfarin therapy requires coagulation monitoring and dose adjustment. Apixaban is an oral factor Xa inhibitor with a rapid onset of action and predictable pharmacokinetics that allow . . .

When used for extended treatment after 6 to 12 months of anticoagulation therapy for venous thromboembolism, the factor Xa inhibitor apixaban reduced the risk of recurrent venous thromboembolism without increasing the risk of serious bleeding. Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular disease–related deaths. 1 The mainstay of treatment is anticoagulation, and guidelines recommend therapy for 3 months or longer. 2 , 3 Decisions about extending treatment are challenging. Although warfarin is effective for the prevention of recurrent venous thromboembolism, the inconvenience of laboratory monitoring and the dietary restrictions, coupled with concerns about bleeding, often lead to a reluctance to continue warfarin therapy beyond 6 to 12 months. Attempts to reduce the risk of bleeding by lowering the intensity of warfarin therapy have resulted in decreased efficacy without . . .

In this clinical trial, apixaban, an oral factor Xa inhibitor, was shown to be superior to enoxaparin for the prevention of thromboembolism after hip replacement, without an increase in the risk of bleeding. Patients undergoing hip-replacement surgery require effective thromboprophylaxis, and low-molecular-weight heparins, vitamin K antagonists, and mechanical methods are now standard therapies. Despite prophylaxis, however, subclinical deep-vein thrombosis develops in approximately 15 to 20% of patients soon after surgery, and symptomatic venous thromboembolism develops in 2 to 4% during the first 3 months after surgery. 1 Practical limitations of current prophylactic techniques have stimulated a search for simpler methods. Low-molecular-weight heparins and fondaparinux require subcutaneous injection. Warfarin has a delayed onset of action and is relatively ineffective soon after surgery. Mechanical methods are cumbersome and relatively ineffective after hip surgery. The development of . . .

Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement. Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed efficacy and safety of these drugs after elective total knee replacement. In ADVANCE-2, a multicentre, randomised, double-blind phase 3 study, patients undergoing elective unilateral or bilateral total knee replacement were randomly allocated through an interactive central telephone system to receive oral apixaban 2·5 mg twice daily (n=1528) or subcutaneous enoxaparin 40 mg once daily (1529). The randomisation schedule was generated by the Bristol-Myers Squibb randomisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four. Investigators, patients, statisticians, adjudicators, and steering committee were masked to allocation. Apixaban was started 12–24 h after wound closure and enoxaparin 12 h before surgery; both drugs were continued for 10–14 days, when bilateral ascending venography was scheduled. Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis, non-fatal pulmonary embolism, and all-cause death during treatment. The statistical plan required non-inferiority of apixaban before testing for superiority; analysis was by intention to treat for non-inferiority testing. The study is registered at ClinicalTrials.gov, number NCT00452530. 1973 of 3057 patients allocated to treatment (1528 apixaban, 1529 enoxaparin) were eligible for primary efficacy analysis. The primary outcome was reported in 147 (15%) of 976 apixaban patients and 243 (24%) of 997 enoxaparin patients (relative risk 0·62 [95% CI 0·51–0·74]; p<0·0001; absolute risk reduction 9·3% [5·8–12·7]). Major or clinically relevant non-major bleeding occurred in 53 (4%) of 1501 patients receiving apixaban and 72 (5%) of 1508 treated with enoxaparin (p=0·09). Apixaban 2·5 mg twice daily, starting on the morning after total knee replacement, offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin, without increased bleeding. Bristol-Myers Squibb; Pfizer.

Low-Dose Aspirin and Recurrent Thromboembolism Results from the ASPIRE trial add evidence supporting the use of low-dose daily aspirin for preventing recurrent venous thromboembolism in patients who have had an initial unprovoked clotting episode. Patients who have had a first episode of unprovoked venous thromboembolism are at high risk for recurrence after anticoagulant therapy is discontinued. 1 – 4 Long-term treatment with a vitamin K antagonist is very effective in preventing a recurrence of venous thromboembolism while treatment continues 5 but has not been shown to improve survival, is associated with a substantially increased risk of bleeding, and is inconvenient for patients. 6 – 10 Consequently, many patients who have had a first episode of unprovoked venous thromboembolism discontinue anticoagulant therapy after 3 to 6 months despite recommendations to prolong therapy. 5 Low-dose aspirin is a simple, inexpensive, and widely . . .

This noninferiority trial compared enoxaparin, a subcutaneously administered, low-molecular-weight heparin, with apixaban, an orally active inhibitor of factor Xa, for thromboprophylaxis after major knee surgery. Statistically, the noninferiority of apixaban was not demonstrated, but its use was associated with lower rates of clinically relevant bleeding. Statistically, the noninferiority of apixaban was not demonstrated, but its use was associated with lower rates of clinically relevant bleeding. The use of heparins, vitamin K antagonists, and mechanical methods to prevent venous thromboembolism after major joint surgery is now standard practice. 1 Despite effective prophylaxis, subclinical venous thrombosis develops soon after surgery in 15 to 20% of patients who undergo hip replacement and in 30 to 40% of those who undergo knee replacement 2 ; symptomatic venous thromboembolism develops within 3 months after surgery in 2 to 4% of patients undergoing hip or knee replacement. 3 , 4 Currently available prophylactic methods have practical limitations, since they require subcutaneous injection (the heparins) or careful dose adjustment (vitamin K antagonists) or tend to be . . .

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.

Venous thromboembolism remains an important complication of hip-replacement surgery, despite the use of preventive measures. The challenge is to reduce the incidence of this potentially fatal but preventable disease further. Current prophylactic treatments include low-molecular-weight heparins, adjusted-dose subcutaneous heparin, and warfarin. 1 , 2 Standard heparin and low-molecular-weight heparins are heterogeneous compounds, derived from animals, that have the potential to induce antiplatelet antibodies and associated thrombotic events and to impair hemostasis through complex effects on platelet function. Org31540/SR90107A, the first compound in a new class of synthetic oligosaccharides with antithrombotic effects, is a selective, antithrombin-dependent, indirect inhibitor of activated factor X (factor . . .

Rivaroxaban is an orally active direct factor Xa inhibitor used to treat venous thromboembolism with approved starting dose of 15 mg twice-daily. We present a case of an accidental overdose in a patient with pulmonary thromboembolism, when the patient received two 150 mg doses of rivaroxaban, instead of 15 mg as prescribed, given 12 hours apart. This error was recognised ten minutes after the second dose, when 50 gm oral activated charcoal was given. Rivaroxaban was stopped and rivaroxaban concentrations, INR, and APTT were monitored. The overdose was uncomplicated and 15 mg twice-daily rivaroxaban was restarted on day two. Apparently unlikely and potentially hazardous dispensing errors do happen. Each oral anticoagulant has a different dosing schedule. In our patient, the prescription for 15 mg twice-daily rivaroxaban was misread as 150 mg twice-daily (a correct dose for dabigatran in atrial fibrillation). Such errors are preventable. Prompt administration of activated charcoal under monitoring of a specific rivaroxaban assay can greatly help management of unusual situations like this one.

Despite evidence-based guidelines for venous thromboembolism (VTE) prevention after total hip or knee arthroplasty (THA/TKA), many patients may not receive effective prophylaxis. Our objective was to analyze data from the multinational Global Orthopaedic Registry (GLORY) to evaluate the compliance of surgeons with the American College of Chest Physicians (ACCP) guidelines for VTE prevention. Data from 8160 patients who had undergone a primary, unilateral, elective THA (n = 3950) or TKA (n = 4210), and had at least 3 months of follow-up were analyzed. Almost all patients received a form of recommended prophylaxis. Compliance with guidelines in terms of type, duration, start time, and dose was achieved for 47% of THA and 61% of TKA patients in the USA, and 62% of THA and 69% of TKA patients outside the USA. Warfarin use, mostly in the USA, was fully compliant in 33% of THA and 48% of TKA patients. Low-molecular-weight heparin use was fully compliant in 63% of THA and 72% of TKA patients in the USA, and 67% of THA and 73% of TKA patients outside the USA. Although almost all THA and TKA patients both inside and outside the USA received prophylaxis, a large proportion did not receive treatment in accordance with the ACCP guidelines. Our study may have overestimated the use of recommended prophylaxis as some participating investigators may have had a specific interest in VTE prophylaxis. Furthermore, although analyses were restricted to approximately three-quarters of patients who had outpatient follow-up data, their characteristics were similar to those in the entire population.