Safety and Effectiveness of Apixaban Compared to Warfarin in Secondary Prevention in Patients With Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study are 1) to characterize the primary and secondary prevention patients, 2) to calculate incidence rates of stroke/SE or major bleeding in each cohort and 3) to investigate for Japanese secondary prevention patients as Real World Evidence (RWE) on the effectiveness and safety of apixaban compared to warfarin in patients with non-valvular atrial fibrillation (NVAF).

Detailed Description
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Japanese population has shown to have higher rate of incidence of stroke and stroke mortality is also higher. Patients with a history of ischemic stroke are at high risk of recurrence and require more rigorous management to prevent recurrence. The same is true for patients with non-valvular atrial fibrillation (NVAF) and treatment with anticoagulants reduces the risk of recurrent embolic stroke. However, some patients still suffer from recurrent embolic and/or ischemic stroke even if they are on anticoagulants for secondary prevention. In addition to the recurrent stroke, risk of bleeding is also higher in the patients with a history of stroke because they are often chronically treated with antiplatelet agents to prevent recurrence after cerebral infarction and with an anticoagulant after embolic stroke. Concomitant use of anticoagulant and anti-platelet agents is sometimes necessary if patients with AF experience cerebral infarction and the risk of bleedings largely enhances in these patients. Thus, patients in secondary prevention are at higher risk of both recurrent ischemic stroke and more effective and safer antithrombotic therapy should take this into account. The purpose of this study are 1) to characterize the primary and secondary prevention patients, 2) to calculate incidence rates of stroke/SE or major bleeding in each cohort and 3) to investigate for Japanese secondary prevention patients as RWE on the effectiveness and safety of apixaban compared to warfarin in patients NVAF.

Official Title
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Safety and Effectiveness of Apixaban Compared to Warfarin in Secondary Prevention in Patients With NVAF With a History of Stroke or Transient Ischemic Attack - a Nationwide Retrospective Observational Study Using Claims Data in Japan

Conditions
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Non-valvular Atrial Fibrillation

Intervention / Treatment
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* Drug: Apixaban
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must meet all the following selection criteria Patients registered in the Medical Data Vision (MDV) database 2008 though 2021. Patients newly with non-valvular atrial fibrillation Patients who newly receive warfarin or apixaban after diagnosis of NVAF Age 20 years or older on the index date Patients who have a history of stroke or transient ischemic attack (TIA) are inclusion criteria only for secondary prevention cohort, otherwise patients will be concluded in the primary prevention cohort. Exclusion Criteria: Patients who meet the following exclusion criteria will be excluded from this study Patients with a diagnosis of valvular AF (standard disease code: 8846941), postoperative AF (8847772), AF associated with mechanical valve malfunction (T82.0), mechanical complication of heart valve prosthesis (T82.0), or rheumatic AF (I05-I09) during the baseline period. Patients with a diagnosis of venous thromboembolism (VTE) during the baseline period Patients who are prescribed any anticoagulants before index date. Patients who are prescribed anticoagulants other than warfarin and apixaban on the index date Patients who are continuously hospitalized due to the first incidence of stroke or other serious diseases.
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 cohort (Reference)<br>Patients with NVAF treated with warfarin | Drug: Warfarin<br>* This is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.<br>|
| Apixaban cohort<br>Patients with NVAF treated with apixaban | Drug: Apixaban<br>* This is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to incidence of a composite of stroke and systemic embolism | Primary effectiveness endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of major bleeding | Primary safety endpoint Major bleeding is defined as any bleeding requiring hospitalization. | Maximum of 14 years (From 2008 to 2021) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to incidence of cardiogenic cerebral embolism | Secondary effectiveness endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of cerebral infarction | Secondary effectiveness endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of hemorrhagic stroke | Secondary effectiveness endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of intracranial hemorrhage | Secondary safety endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of gastrointestinal bleeding | Secondary safety endpoint | Maximum of 14 years (From 2008 to 2021) | 
| Time to incidence of intraocular bleeding | Secondary safety endpoint | Maximum of 14 years (From 2008 to 2021) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Non-valvular atrial fibrillation, Apixaban, Warfarin, Secondary prevention