Validation of International Warfarin Pharmacogenetics Consortium (IWPC) Algorithm in Elderly Patients With Comorbidity

Study Overview
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Brief Summary
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The purpose of this study is to validate the International Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of elderly people (65 years or older) with heart valves and/or nonvalvular atrial fibrillation (AF) and at least one comorbid condition, and to assess the algorithm's prognostic relevance.

Official Title
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Prospective Validation of IWPC Pharmacogenetic Algorithm for Estimating the Appropriate Initial Dose of Warfarin in Elderly People (65 or Older) With Heart Valves Prostheses or Non Valvular Atrial Fibrillation and Comorbidity

Conditions
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Atrial Fibrillation, Thrombus Due to Heart Valve Prosthesis

Intervention / Treatment
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* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 65 years Patients who initiate warfarin because of non valvular atrial fibrillation or heart valve replacement At least one comorbid condition At least two other drugs regularly assumed over and above warfarin Exclusion Criteria: Presence of systemic coagulopathies Presence of malignancies needing chemotherapy Inability or refusal to give informed consent

Ages Eligible for Study
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Minimum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Warfarin in elderly with comorbidity<br>Patients 65 years or older, candidate for therapy with warfarin for non valvular atrial fibrillation or heart valve replacement | Drug: Warfarin<br>* warfarin treatment will be determined by treating physicians according to in-hospital guidelines, blindly to genotype assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients whose predicted dose of warfarin is within 20% of the actual stable therapeutic dose. | stable warfarin dosing is defined as the mean daily does required to achieve three or more consecutive International Normalized Ratio (INR) measurements within the individual's target range, at the same daily does. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients for whom the predicted dose is at least 20% higher than the actual dose (overestimation) or at least 20% lower than the actual dose (underestimation). |  | up to 12 months | 
| number of cardiovascular and cerebrovascular events | composite endpoint: death for any cause, hospitalization for cardiovascular and cerebrovascular events, major bleeding or thromboembolism | 12 months | 
| number of patients with major bleeding events | major bleeding: (i) fatal bleeding; and/or (ii) symptomatic bleeding in a critical area or organ; and/or (iii) bleeding causing a fall in haemoglobin level of ≥2 g/dL or leading to transfusion of two or more units of blood or red cells. | 12 months | 
| number of thromboembolic event | thromboembolism is defined as occurrence of cerebral infarction, myocardial infarction, peripheral arterial embolism. | 12 months | 
| number of cardiovascular and cerebrovascular events |  | 4 weeks | 
| number of patient reported episodes of minor bleeding events |  | one year | 
| average maintenance dose per patient |  | 12 months | 
| time to achievement of stable warfarin dosing from initiation |  | up to 12 months | 
| time to therapeutic INR per patient | defined as the time of first achieving INR measurement within the individual's target range, providing that INR is also within the target range at the subsequent clinic visit | up to 12 months | 
| percentage time in the therapeutic INR range |  | up to 3 months | 
| percentage time in the therapeutic INR range |  | four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warfarin, International Warfarin Pharmacogenetics Consortium algorithm, Atrial Fibrillation, Heart Valve Prosthesis Implantation, elderly, comorbidity