North American Thrombosis Forum, AF Action Initiative Consensus Document.

The North American Thrombosis Forum Atrial Fibrillation Action Initiative consensus document is a comprehensive yet practical briefing document focusing on stroke and bleeding risk assessment in patients with atrial fibrillation, as well as recommendations regarding anticoagulation options and management. Despite the breadth of clinical trial data and guideline recommendation updates, many clinicians continue to struggle to synthesize the disparate information available. This problem slows the uptake and utilization of updated risk prediction tools and adoption of new oral anticoagulants. This document serves as a practical and educational reference for the entire medical community involved in the care of patients with atrial fibrillation.

Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.

We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.

Enoxaparin monotherapy without oral anticoagulation to treat acute symptomatic pulmonary embolism.

Conventional anticoagulation for symptomatic pulmonary embolism consists of continuous intravenous unfractionated heparin as a "bridge" to oral anticoagulation. This strategy requires 5 days or more of intravenous heparin while oral vitamin K antagonists gradually achieve a therapeutic effect. Oral vitamin K antagonists require frequent blood testing to optimize dosing, and their interactions with other medications and foods make regulation difficult. Therefore we tested a different approach to therapy: long-term enoxaparin monotherapy. We randomized 60 symptomatic pulmonary embolism patients in a 2:1 ratio to 90 days of enoxaparin as monotherapy without warfarin (N=40) or to intravenous unfractionated heparin as a "bridge" to warfarin, target INR 2.0-3.0 (N=20). Enoxaparin patients received 1 mg/kg twice daily for 14 days during the acute phase followed by randomized assignment during the chronic phase to 1.0 mg/kg vs. 1.5 mg/kg once daily. In an intention-to-treat analysis, 3 of the 40 enoxaparin patients developed recurrent venous thromboembolism compared with 0 of 20 standard therapy patients (p = 0.54). One of the 40 enoxaparin patients had a major hemorrhagic complication compared with 2 of the 20 standard therapy patients (p = 0.26). Median hospital length of stay was shorter with enoxaparin compared to standard therapy (4 vs. 6 days) (p = 0.001). Following our study we can conclude that extended 3-month treatment with enoxaparin as monotherapy for symptomatic, acute pulmonary embolism is feasible and warrants further study in a large clinical trial.