Association Between Genetic Variant Scores and Warfarin Effect

Study Overview
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Brief Summary
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Study objective is to determine whether there is an association between genetic variant risk scores and clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, bleeding event, ischemic stroke, death) in participants taking warfarin for atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), and/or intracardiac thrombosis.

Detailed Description
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It is anticipated that next generation genomic sequencing will identify rare genetic variants in ethnically diverse populations, which otherwise would not have been detected using commercially available warfarin tests. Furthermore, retrospective review of clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, major bleeding event, ischemic stroke) of study participants will determine the clinical utility of genetic variant risk scores. Study outcomes will provide guidance on future directions for optimizing dosing algorithms for warfarin that combine pharmacogenetic principles with clinical dosing.

Official Title
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Association Between Risk Scores for Genetic Variants and Percentage of Time in Therapeutic Range for Participants With Atrial Fibrillation, Deep Vein Thrombosis, and/or Intracardiac Thrombosis Taking Warfarin

Conditions
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Atrial Fibrillation, Deep Vein Thrombosis, Intracardiac Thrombus, Pulmonary Embolism, Venous Thromboembolic Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-valvular atrial fibrillation Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) with no hypercoagulable condition Non-valvular atrial fibrillation and DVT/PE (with no hypercoagulable condition) Intracardiac thrombosis (i.e. apical thrombosis, atrial thrombosis, auricular thrombosis, mural thrombosis, and/or ventricular thrombosis) Age 18-99 years Signed informed consent Exclusion Criteria: Presence of a mechanical heart valve Failure to provide signed informed consent Known diseases that affects coagulation test results such as vitamin K deficiency, disseminated intravascular coagulopathy, Von Willebrand disease, hemophilia, liver failure, etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent time in therapeutic range during initial 12 weeks of warfarin | Within the 12 weeks of treatment, this is the percentage of time that a given participant is within the therapeutic range (e.g. participant is in therapeutic range 75% of time/12 weeks of measurement) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach therapeutic INR | Time needed to achieve first INR within the range of 2 to 3, provided that subsequent INR ≥ 7 days later was also within the range of 2 to 3 | 12 weeks | 
| INR ≥ 4.0 during first 12 weeks of warfarin therapy | Time greater than the desired INR therapeutic range within the first 12 weeks of warfarin therapy | 12 weeks | 
| Ischemic stroke | Development of a clinical diagnosis of an ischemic stroke | 12 weeks | 
| Major bleeding event during first 12 weeks of warfarin therapy | Development of a major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician | 12 weeks | 
| Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy | Development of a clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warfarin, Coumadin, Pharmacogenomics, Pharmacogenetics, Adverse Drug Reactions, Bleeding/hemorrhaging