Treatment Patterns and Bleeding Risk of Anticoagulants in Patients With Venous Thromboembolism in Korea

Study Overview
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Brief Summary
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This study is a retrospective, observational, nationwide population-based cohort study utilizing the South Korea's Health Insurance and Review Assessment Service (HIRA) database. The aims of this study are to describe the sociodemographic and clinical characteristics of patients with venous thromboembolism according to their anticoagulant treatment (parenteral anticoagulants, warfarin, or non-vitamin K antagonist oral anticoagulants), to describe the treatment patterns related to anticoagulants, and to examine the risk of major bleeding according to the specific type of oral anticoagulants. The study will be conducted in two phases: Phase I for descriptive study and Phase II for comparative study.

Official Title
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Treatment Patterns and Clinical Outcomes Among Venous Thromboembolism Patients Treated With Anticoagulants After the Entry of Non-vitamin K Antagonist Oral Anticoagulants in Korea

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Parenteral anticoagulant
* Drug: Warfarin
* Drug: Apixaban
* Drug: Rivaroxaban
* Drug: Dabigatran
* Drug: Edoxaban


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Incident VTE diagnosis in an inpatient or outpatient setting between 1 Mar 2013 and 30 Jun 2019 Received anticoagulation therapy (all medication codes for anticoagulants approved for VTE in Korea; UFH, LMWH, warfarin, and NOACs) within 30 days of their VTE diagnosis (the index date will be defined as the date of treatment initiation with anticoagulants) Aged ≥18 years at index date Exclusion Criteria: Had a record of VTE diagnosis within the 12-month period prior to the index VTE encounter. Diagnosed with atrial fibrillation/flutter, mechanical heart valve replacement or mitral stenosis anytime prior to index date Had a record of Inferior Vena Cava filter anytime prior to index date Received anticoagulatory therapy within the 12-month period prior to index VTE encounter Prescribed two different anticoagulants on the same index date Had a record of pregnancy within the 9-month period prior to index date Had a record of active cancer within the past 6 months of period prior to index date

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Parenteral anticoagulant only<br>LMWH, UFH | Drug: Parenteral anticoagulant<br>* Parenteral anticoagulant only<br>|
| Warfarin-based<br>Warfarin only + parenteral anticoagulant bridged warfarin | Drug: Warfarin<br>* Warfarin-based<br>|
| NOAC-based<br>NOAC only + parenteral anticoagulant bridged NOAC NOAC: apixaban, rivaroxaban, dabigatran, edoxaban | Drug: Apixaban<br>* Apixaban<br>Drug: Rivaroxaban<br>* Rivaroxaban<br>Drug: Dabigatran<br>* Dabigatran<br>Drug: Edoxaban<br>* Edoxaban<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Interruption in Index Anticoagulant Treatment | Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment interruption, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Time to Treatment Interruption | Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. The time to treatment interruption was defined as the period from the index date to the date of treatment interruption. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment interruption, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants Who Switched to Another Anticoagulant Therapy | Treatment switching was defined as a prescription of another anticoagulant therapy that was started after the treatment initiation of the index anticoagulant treatment and within 30 days after the estimated end of supply of the index anticoagulant drug (exposure to the new anticoagulant treatment must last for at least 30 days to be considered as a treatment switch). The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment switch, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Time to Treatment Switch | Treatment switching was defined as a prescription of another anticoagulant therapy that was started after the treatment initiation of the index anticoagulant treatment and within 30 days after the estimated end of supply of the index anticoagulant drug (exposure to the new anticoagulant treatment must last for at least 30 days to be considered as a treatment switch). The time to treatment switch was defined as the period from the index date to the date of treatment switch. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment switch, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants Who Completely Discontinued Index Anticoagulant Treatment | Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment discontinuation, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Time to Treatment Discontinuation | Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The time to treatment discontinuation was defined as the period from the index date to the date of treatment discontinuation. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to treatment discontinuation, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Overall Index Anticoagulant Treatment Duration | Overall anticoagulant treatment duration was defined as the time period from the index date to the earliest of treatment interruption, switch, or discontinuation. Treatment interruption: when a participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after this period of 30 days. Treatment switching: a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Treatment discontinuation: when a participant who ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. The index date was defined as the date of first prescription for anticoagulants within 30 days after the index VTE event. | From index date up to the earliest of treatment interruption, switch, or discontinuation; during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 3 Months | Participants were considered to be persistent on index anticoagulant treatment if a participant had evidence of a repeat prescription within 30 days of the end of their prescription and does not experience any of the events that included treatment interruption (participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after 30 days), switch (prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug), or discontinuation (participant ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time). Index date: date of first prescription for anticoagulants within 30 days after the index VTE event. | Within 3 months of index date, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants Who Were Persistent on Index Anticoagulant Treatment for 6 Months | Participants were considered to be persistent on index anticoagulant treatment if a participant had evidence of a repeat prescription within 30 days of the end of their prescription and does not experience any of the events that included treatment interruption (participant had a gap with no new treatment within 30 days of estimated end of supply of index treatment, but subsequently restarted index treatment after 30 days), switch (prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug), or discontinuation (participant ended their first continuous treatment episode with index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time). Index date: date of first prescription for anticoagulants within 30 days after the index VTE event. | Within 6 months of index date, during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Interruption | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment interruption. Treatment interruption was defined as when a participant had a gap with no new treatment within 30 days of the estimated end of supply of index treatment, but subsequently restarted the index treatment after this period of 30 days. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. | Within 30 days before treatment interruption during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Bleeding | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event major bleeding are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Complications of VTE | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event complications of VTE are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Thromboembolism | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event thromboembolism are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Major Surgery | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event major surgery are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Cancer-related Event | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event cancer-related event are reported among participants without active cancer. Data not collected and reported for participants with active because all participants already had cancer. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Kidney Function Change | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event kidney function change are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Switch From Index Anticoagulant Treatment: Liver Function Change | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment switch. Treatment switching was defined as a prescription of another anticoagulant therapy that was started after treatment initiation of index anticoagulant treatment and within 30 days after estimated end of supply of index anticoagulant drug. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. In this outcome measure, results for event liver function change are reported. | Within 30 days before treatment switch during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 
| Number of Participants With Clinical Events Preceding Index Anticoagulant Treatment Discontinuation | Clinical event preceding first treatment change was defined as occurrence of any event (major bleeding, complications of VTE, thromboembolism, major surgeries, cancer-related event, kidney function change, liver function change) within 30 days before treatment discontinuation. Treatment discontinuation (complete discontinuation; no reinitiation) was defined as when a participant who ended their first continuous treatment episode with the index anticoagulant treatment without switching, and subsequently have no further prescriptions for that respective anticoagulant treatment during all available follow-up time. Index date was defined as date of first prescription for anticoagulants within 30 days after index VTE event. | Within 30 days before treatment discontinuation during observation period of maximum up to 88 months (retrospective data was retrieved and observed during 1 month of this study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous thromboembolism, anticoagulant, treatment pattern, bleed