Warfarin Initiation in Mechanical Mitral Valve Replacement Patients

Study Overview
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Brief Summary
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A prospective, comparative study evaluating warfarin initiation in a dose of 3mg versus 5mg in mechanical mitral valve prostheses patients who received anticoagulation with warfarin with the use of enoxaparen as a bridging agent .Fifty patients were included and compared in terms of the primary outcome time to reach therapeutic INR range.Other outcomes includes proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5, total dose of enoxaparin required for bridging, safety related to both doses of anticoagulants used

Detailed Description
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Inpatients of The Cardiovascular hospital who had undergone mitral heart valve replacement with a mechanical prosthesis and commencing warfarin were eligible for inclusion. Patients were included after they had newly undergone elective surgery for implantation of mechanical mitral heart valves, had commenced on warfarin, received enoxaparin as a bridging agent and had INR monitored for a minimum of 4 consecutive days after warfarin initiation. A total of 50 consecutive MVR patients were recruited. Each was assigned to either the group I (25 patients) or the group II (25 patients) group. All patients received the conventional postoperative treatment including: Diuretics, beta-blockers, digoxin or heart rate-regulating calcium channel blockers and anticoagulation bridging therapy using LMWH according to the European Society of Cardiology (ESC) Guidelines for the management of MVR and antibiotic for 48hour after surgery according to the investigator's hospital's antibiotic protocol. Baseline evaluation included demographics and history taking. After obtaining the informed consent, information including age, weight, height, smoking state, and other diseases e.g. hypertension, diabetes, hyperlipidemias, etc. were documented for each patient. Medication history in details, as well as the background cardiovascular treatment was considered. Blood samples were withdrawn from patients for evaluation of INR. Complete blood count, kidney and liver function tests were performed as part of the routine admission care. All patients were followed up daily post operative till reaching an in range INR value. All patients were observed daily for INR values and dose adjusted accordingly and also estimation of incidence and severity of bleeding complications was done.

Official Title
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Evaluation of Warfarin Initiation at 3mg Versus 5mg for Anticoagulation of Mechanical Mitral Valve Replacement Patients

Conditions
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Mitral Valve Disease

Intervention / Treatment
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* Drug: Warfarin Sodium 5 MG
* Drug: Warfarin Sodium 3 MG
* Drug: Enoxaparin Sodium 100 MG/ML Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New mechanical mitral valve prostheses patients who will receive anticoagulation with warfarin with the use of enoxaparen as a bridging agent. Exclusion Criteria: Pregnant or lactating women Renal disorder (GFR = 45< mL/min) or patients on renal dialysis Hepatic disorder (Child Pugh class B or C) Clinically significant active bleeding. Recurrent DVT or PE. Baseline INR >1.2 Asian ancestry Cancer Impaired nutritional status Alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>a group of 25 patients received 5mg Marevan ® tablets as initiation warfarin dose in combination of enoxaparin (Clexane® ) as a bridging agent.INR was monitored daily and dose adjustments were done to reach therapeutic INR range (2-3) at which the Enoxaparen was discontinued.Follow up was continued till first INR reading in therapeutic range. Bleeding events due to overanticoagulation were monitored through the follow up period. | Drug: Warfarin Sodium 5 MG<br>* warfarin sodium 5mg tablets<br>* Other names: Marevan 5mg;Drug: Enoxaparin Sodium 100 MG/ML Prefilled Syringe<br>* Clexane® Syringes 2,000 IU (20 mg)/0.2 ml solution for injection in pre-filled syringes. Clexane® Syringes 4,000 IU (40 mg)/0.4 ml solution for injection in pre-filled syringes. Clexane® Syringes 6,000 IU (60 mg)/0.6 ml solution for injection in pre-filled syringes. Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes. Dose was determined individually for each patient as 1mg/kg every 12 hours.<br>* Other names: Clexane;|
| Experimental: Group II<br>a group of 25 patients received 3mg Marevan ® tablets as initiation warfarin dose in combination of enoxaparin (Clexane® ) as a bridging agent.INR was monitored daily and dose adjustments were done to reach therapeutic INR range (2-3) at which the Enoxaparen was discontinued.Follow up was continued till first INR reading in therapeutic range. Bleeding events due to overanticoagulation were monitored through the follow up period. | Drug: Warfarin Sodium 3 MG<br>* warfarin sodium 3mg tablets<br>* Other names: Marevan 3mg;Drug: Enoxaparin Sodium 100 MG/ML Prefilled Syringe<br>* Clexane® Syringes 2,000 IU (20 mg)/0.2 ml solution for injection in pre-filled syringes. Clexane® Syringes 4,000 IU (40 mg)/0.4 ml solution for injection in pre-filled syringes. Clexane® Syringes 6,000 IU (60 mg)/0.6 ml solution for injection in pre-filled syringes. Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes. Dose was determined individually for each patient as 1mg/kg every 12 hours.<br>* Other names: Clexane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of warfarin initiating dose and the corresponding dosing schedule: Time to reach therapeutic INR range (TTR) | Time to reach therapeutic INR range (TTR):The time in days required for the patient from the start of warfarin initiation till reaching the therapeutic | 4-16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of overanticoagulation | Proportion of patients who achieved the target INR of 2.0-3.0 between day 3 and day 5 | from 3 to 5 days | 
| Anticoagulation Safety evaluation | Incidence of major and minor bleeding events | from 4 to 16 days | 
| Low Molecular Weight Heparin consumption | The total dose of enoxaparin in mg that the patient received till discontinuation of bridging | from 4 to 16 days | 
| The Overall cost evaluation | total cost spent in LE during the follow up period calculated by the summation of the cost of treatment , cost of bleeding event management and cost of hospital stay. | from 4 to 16 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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warfarin, anticoagulation, mitral valve replacement