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Proposal 1160

Title of the Proposed Research

Development of a clinical decision support tool to identify patients at high risk of early or late bleeding complications from anticoagulation

Lead Researcher

Mark H. Ebell MD, MS

Affiliation

Department of Epidemiology and Biostatistics
College of Public Health
University of Georgia

Funding Source

None

Potential Conflicts of Interest

Potential conflicts of interest will be disclosed when the research is presented and published.

Data Sharing Agreement Date

3 June 2015

Lay Summary

The most important complication of anticoagulation is an increased risk of bleeding complications. These complications are most likely to occur early in the course of treatment, especially in the first 3 months. However, this risk persists, and varies from patient to patient. Previous studies have examined the accuracy of simple point scores such as the Outpatient Bleeding Risk Index (1), ATRIA score (2), HAS-BLED score (3), and HEMORRHAGES score (4). However, they were largely developed in patients taking warfarin, and used standard multivariate techniques. Some have also not been found to be as accurate in subsequent studies.

Dabigatran is a new, widely used oral anticoagulant. It has the important advantages of a similar safety profile, better efficacy than warfarin for some conditions, and much greater ease of use by patients. We propose to evaluate the existing clinical decision rules for their ability to identify patients at increased risk of bleeding when placed on dabigatran. These patients could potentially benefit from closer monitoring, especially during the first 3 months of therapy.

We will also investigate novel approaches to developing clinical decision support tools such as classification and regression trees (CART) and artificial neural networks (ANN). These have the potential to more clearly identify patients at risk for bleeding complications. Thus our specific aims are:

1. Evaluate the accuracy of existing clinical decision rules for the prediction of bleeding complications in patients taking dabigatran or warfarin.
2. Develop new decision support tools using regression, CART and/or ANN methodologies.

We will summarize the findings in published research studies in peer reviewed medical journals. Each article will include the decision support tool in full, which will be available for use by clinicians and their patients. The results will help patients and their doctors identify who needs special monitoring to avoid bleeding complications.

1. Pisters R, Lane DA Nieuwlaat, et al. A novel user-friendly score (HAS-BLED) to assess 1 year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey. Chest 2010; 138(5): 1093-1100. Also: J Am Coll Cardiol 2011; 57: 173-80.
2. Fang MC, et al. A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study. J Am Coll Cardiol 2011; 58: 395-401
3. Wells PS, Forgie MA, Simms M, et al. The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for DVT and PE. Arch Intern Med 2003; 163: 917-20.
4. Gage BF, et al. Clinical classification schemes for predicting hemorrhage: Results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151: 713-9

Study Data Provided

Study 1160.26: Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) With Dabigatran Etexilate
Study 1160.46: Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)
Study 1160.53 (RE-COVER): Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism
Study 1160.20: PETRO Stroke Prevention in Patients With AF by Treatment With Dabigatran, With and Without Aspirin, Compared to Warfarin
Study 1160.49: A Dose Response Study of Dabigatran Etexilate (BIBR 1048) in Pharmacodynamics and Safety in Patients With Non-valvular Atrial Fibrillation in Comparison to Warfarin
Study 1160.113: Dabigatran Etexilate in Patients With Mechanical Heart Valves (RE-ALIGN)
Study 1160.42: Long-term, Open-label Follow-up Treatment of Patients With A-fib Who Have Been Previously Treated With BIBR 1048
Study 1160.63 (RE-SONATE): Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE
Study 1160.47 (RE-MEDY): Secondary Prevention of Venous Thrombo Embolism (VTE)

Statistical Analysis Plan

The statistical analysis plan will be added after the research is published.

Publication Citation