Search

The efficiency and the safety of a continuous use of vitamin K for prophylaxis against the venous thromboembolism with idraparinux in various patients were examined. The results showed that though idraparinux helps in preventing recurrent thromboembolism, it also increases the risks of a major hemorrhage.

The article presents an update of the 2004 consensus guidelines of the Australasian Society of Thrombosis and Haemostasis (ASTH). It states that the guideline offers strategies to prevent the over-administration of warfarin, reversal of warfarin, and connecting the therapy in different clinical settings. It cites the importance of considering the risk of thrombosis relative to risk of bleeding. It also mentions that warfarin can be restarted on the evening of surgery.

Risks of recurrence and bleeding are highest during the first weeks of anticoagulant therapy for venous thromboembolism (VTE). We therefore examined the early time course of recurrence and major bleeding in a pre-specified sub-analysis of the AMPLIFY trial, a randomised, double-blind, six-month comparison of oral apixaban with conventional therapy (enoxaparin followed by warfarin) in 5,395 patients with symptomatic proximal deep-vein thrombosis or pulmonary embolism. Early events were of particular interest because apixaban was given without initial heparin treatment. The primary efficacy and safety outcomes were the incidences of the adjudicated composite of recurrent symptomatic VTE or death related to VTE, and of adjudicated major bleeding, respectively. This analysis reports on recurrence and bleeding after 7, 21, and 90 days of therapy, in addition to the previously reported end-of-study results. These were the times specified before statistical analysis. Recurrent VTE after 7, 21, and 90 days, and six months had occurred in 18 (0.7%), 29 (1.1%), 46 (1.8%), and 59 patients (2.3%), respectively, given apixaban, and in 23 (0.9%), 35 (1.3%), 58 (2.2%), and 71 patients (2.7%), respectively, given conventional therapy. Major bleeding had occurred during these time intervals in 3 (0.1%), 5 (0.2%), 11 (0.4%), and 15 patients (0.6%), respectively, who received apixaban, and in 16 (0.6%), 26 (1.0%), 38 (1.4%), and 49 patients (1.8%), respectively, given conventional therapy. Efficacy of apixaban was non-inferior at each time point, with no excess of early recurrences. The reduced bleeding risk associated with apixaban began early during the course of treatment.

Background: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism., Methods: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding., Results: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups., Conclusions: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

Background: Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring., Methods: We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study., Results: The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin-vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11)., Conclusions: Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation. (Funded by Bayer Schering Pharma and Ortho-McNeil; ClinicalTrials.gov numbers, NCT00440193 and NCT00439725.).

Background: Venous thromboembolism is treated with unfractionated heparin or low-molecular-weight heparin, followed by a vitamin K antagonist. We investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy., Methods: We conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal)., Results: In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement., Conclusions: In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy. (ClinicalTrials.gov numbers, NCT00067093 [ClinicalTrials.gov] and NCT00062803 [ClinicalTrials.gov].)., (Copyright 2007 Massachusetts Medical Society.)

Objective: To examine the time taken to reach a stable international normalized ratio (INR), as well as the incidence of overanticoagulation of an age-adjusted warfarin initiation protocol., Methods: Inpatients and outpatients commencing warfarin therapy at 2 teaching hospitals were dosed according to the age-adjusted protocol. Data were collected prospectively., Main Outcome Measures: Time to reach a stable INR of 2-3 and the number of patients experiencing an INR > or =4 during the first week of warfarin therapy., Results: Seventy-three patients were assessed; at the completion of the 4-day titration protocol, 63% had achieved a stable INR. After an additional 2 days of empiric dosage adjustment by the attending physician, 86% of the subjects demonstrated a stable INR. Five patients (7%) experienced an INR > or =4. These patients had a nonsignificant trend toward a lower plasma albumin level compared with other patients (p = 0.057, Student's t-test). The INR-driven dose adjustments on days 3 and 4 of this protocol coped with other variables that have been shown to affect maintenance warfarin dosing. These included weight, gender, pharmacologic factors affecting clearance, and the presence of certain predesignated risk factors., Conclusions: The age-adjusted dosing protocol rapidly achieved a stable INR with minimal overanticoagulation. Patients with low serum albumin levels (<3.0 g/dL) may be sensitive to the effects of warfarin during the loading phase.