Warfarin Dosage Adjustment Model Analysis Study

Study Overview
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Brief Summary
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Despite the wide availability of Direct oral anticoagulation (DOAC), warfarin remains an important oral anticoagulant1 especially in patients with mechanical valve replacement or chronic renal failure where the evidence of DOAC is limited. However, the dosing of warfarin is challenging as it has a narrow therapeutic index and is highly influenced by dietary vitamin K intake and drugs that interacts with cytochrome (CYP) P4501. The time outside therapeutic range will carry the risk of adverse events such as thrombosis and bleeding. Numerous algorithms have been proposed that utilized either clinical or pharmacogenetics factors. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended the use of 4 dosing algorithms. However, these algorithms require the input of genetic information such as CYP2C9 and VKORC1 type which are not widely available locally and are less relevant in maintenance phase. Furthermore, these algorithms target mainly at predicting the initiation and the maintenance dose of warfarin. This has provided us with the opportunities to explore the Prediction model for on-treatment warfarin dose titration for outside therapeutic range.

Detailed Description
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Despite the wide availability of Direct oral anticoagulation (DOAC), warfarin remains an important oral anticoagulant1 especially in patients with mechanical valve replacement or chronic renal failure where the evidence of DOAC is limited. However, the dosing of warfarin is challenging as it has a narrow therapeutic index and is highly influenced by dietary vitamin K intake and drugs that interacts with cytochrome (CYP) P4501. The time outside therapeutic range will carry the risk of adverse events such as thrombosis and bleeding. Numerous algorithms have been proposed that utilized either clinical or pharmacogenetics factors. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended the use of 4 dosing algorithms. However, these algorithms require the input of genetic information such as CYP2C9 and VKORC1 type which are not widely available locally and are less relevant in maintenance phase. Furthermore, these algorithms target mainly at predicting the initiation and the maintenance dose of warfarin. This has provided us with the opportunities to explore the Prediction model for on-treatment warfarin dose titration for outside therapeutic range.

Official Title
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Warfarin Dosage Adjustment for Outside Therapeutic Range: a Linear Regression Model Analysis

Conditions
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Warfarin

Intervention / Treatment
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* Behavioral: Warfarin dosage adjustment model


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been on maintenance warfarin treatment Patients whose INR have fallen outside therapeutic range will be identified using CDARS enquiry Exclusion Criteria: 1. No exclusion criteria
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

| Intervention/Treatment |
| --- |
|Behavioral: Warfarin dosage adjustment model|Warfarin dosage adjustment model use to predict the initiation and the maintenance dose of warfarin. Variation of warfarin dose during stable maintenance phase for the same patient might be influenced more by temporal factors such as modification of drug regimens that utilize the CYP450 pathway, or dietary vitamin K intake|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| extreme outside therapeutic range | INR<1.5 or INR>3.5 on two consecutive blood checking | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the time needed to achieve within therapeutic range | It is calculated by the time interval from the outside therapeutic range INR to final within therapeutic range INR, the number of INRs checking between the initial outside therapeutic range and the final within therapeutic range | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Warfarin, dosage adjustment, therapeutic range, linear regression model