Comparison of a single end point to determine optimal initial warfarin dosing (5 mg versus 10 mg) for venous thromboembolism

There remains considerable controversy regarding optimal initial warfarin dosing in patients with acute venous thromboembolism. Therefore, an open-label, randomized trial comparing 2 warfarin initiation nomograms (5 vs 10 mg) was conducted in patients with acute venous thromboembolism. All participants received fondaparinux for > or = 5 days as a "bridge" to warfarin. The primary end point was defined as the number of days necessary to achieve 2 consecutive international normalized ratio laboratory test values > 1.9. A total of 50 patients were enrolled and randomly assigned to each of the treatment arms. The median time to 2 consecutive international normalized ratios was 5 days in the 2 groups. There was no statistical difference in achieving the primary end point using either the 5- or the 10-mg nomogram (p = 0.69). These results should provide clinicians with increased warfarin dosing options in patients presenting with acute venous thromboembolism.     

Comparison of bleeding in patients with nonvalvular atrial fibrillation treated with ximelagatran or warfarin: assessment of incidence, case-fatality rate, time course and sites of bleeding, and risk factors for bleeding

BACKGROUND: Ximelagatran is a novel direct thrombin inhibitor that can be administered as a fixed oral dose, without the need for anticoagulant monitoring. METHODS: We undertook a pooled analysis of 7329 patients with nonvalvular atrial fibrillation from the Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation III and V trials to compare bleeding outcomes in patients who received ximelagatran, 36 mg twice daily, or warfarin sodium (target international normalized ratio, 2.0-3.0). We determined annual risk of bleeding (any, major), case-fatality rate, time course and anatomic sites of major bleeding, and risk factors for major bleeding with ximelagatran and warfarin treatment. RESULTS: Annual incidence of any bleeding was 31.75% with ximelagatran and 38.82% with warfarin (relative risk reduction, 18.2%; 95% confidence interval [CI], 13.0-23.1; P<.001). Annual incidence of major bleeding was 2.01% with ximelagatran and 2.68% with warfarin (relative risk reduction, 25.1%; 95% CI, 3.2-42.1; P = .03). Case-fatality rate of bleeding was comparable in ximelagatran- and warfarin-treated patients (8.16% vs 8.09%; P = .98). Cumulative incidence of major bleeding was higher with warfarin than ximelagatran after 24 months of treatment (4.7% vs 3.7%; P = .04). Anatomic sites of bleeding were comparable with both treatments. Risk factors for bleeding with ximelagatran were as follows (hazard ratios and 95% CIs in parentheses): diabetes mellitus (1.81; 1.19-2.77; P = .006), previous stroke or transient ischemic attack (1.78; 1.16-2.73; P = .008), age 75 years or greater (1.70; 1.33-2.18; P<.001), and aspirin use (1.68; 1.08-2.59; P = .02). Risk factors for bleeding in warfarin-treated patients were previous liver disease (4.88; 1.55-15.39; P = .007); aspirin use (2.41; 1.69-3.43; P<.001); and age 75 years or greater (1.26; 1.03-1.52; P = .02). CONCLUSIONS: Treatment with ximelagatran, 36 mg twice daily, is associated with a lower risk of bleeding than warfarin in patients with nonvalvular atrial fibrillation. Aspirin use and increasing age were associated with an increased risk of bleeding in ximelagatran- and warfarin-treated patients.     

Risk Stratification Model: Lower-Extremity Ultrasonography for Hospitalized Patients with Suspected Deep Vein Thrombosis

Background

The Wells score for deep venous thrombosis (DVT) has a high failure rate and low efficiency among inpatients.

Objective

To create and validate an inpatient-specific risk stratification model to help assess pre-test probability of DVT in hospitalized patients.

Design

Prospective cohort study of hospitalized patients undergoing lower-extremity ultrasonography studies (LEUS) for suspected DVT. Demographics, physical findings, medical history, medications, hospitalization, and laboratory and imaging results were collected. Samples were divided into model derivation (patients undergoing LEUS 11/1/2012–12/31/2013) and validation cohorts (LEUS 1/1/2014–5/31/2015). A DVT prediction rule was derived using the recursive partitioning algorithm (decision tree-type approach) and was then validated.

Participants

Adult inpatients undergoing LEUS for suspected DVT from November 2012 to May 2015, excluding those with DVT in the prior 3 months, at a 793-bed, urban academic quaternary-care hospital with ~50,000 admissions annually.

Main Measures

The primary outcome was the presence of proximal DVT, and the secondary outcome was the presence of any DVT (proximal or distal). Model sensitivity and specificity for predicting DVT were calculated.

Key Results

Recursive partitioning yielded four variables (previous DVT, active cancer, hospitalization ≥ 6 days, age ≥ 46 years) that optimized the prediction of proximal DVT and yield in the derivation cohort. From this decision tree, we stratified a scoring system using the validation cohort, categorizing patients into low- and high-risk groups. The incidence rates of proximal DVT were 2.9% and 12.0%, and of any DVT were 5.2% and 21.0%, for the low- and high-risk groups, respectively. The AUC for the discriminatory accuracy of the Center for Evidence-Based Imaging (CEBI) score for risk of proximal DVT identified on LEUS was 0.73. Model sensitivity was 98.1% for proximal and 98.1% for any DVT.

Conclusions

In hospitalized adults, specific factors can help clinicians predict risk of DVT, identifying those with low pre-test probability, in whom ultrasonography can be safely avoided.

     

Indomethacin or flurbiprofen treatment of periodontitis in beagles: Comparison of effect on bone loss

The effect of two non-steroidal anti-inflammatory drugs, indomethacin and flurbiprofen, on the progression of periodontal disease was studied in 16 beagle dogs over a 12-month period. Standardized radiographs were used to measure the rate of bone loss. Following a 6-month pretreatment baseline period, 5 dogs were dosed daily with 1.0 mg/kg indomethacin, 5 dogs were dosed daily with 0.02 mg/kg flurbiprofen, and 6 dogs were dosed with empty gelatin capsules for a 6-month period. In the untreated control dogs, the rate of bone loss in the treatment period significantly increased from baseline. In contrast, the rate of bone loss significantly decreased from baseline in the flurbiprofen-treated dogs. In the indomethacin-treated dogs, rate of bone loss in the treatment period was not significantly different from baseline. The data indicate that both flurbiprofen and indomethacin inhibit alveolar bone loss in beagles compared to untreated controls. The data also indicate that with the dosages employed flurbiprofen is overall more effective.