Study to Learn More About the Benefits and Side-effects of Drugs Rivaroxaban and Apixaban Compared to the Drug Warfarin for Stroke Prevention in Patients With Rapid and Irregular Heartbeat Which is Not Due to a Heart-valve Fault (Non-valvular Atrial Fibrillation) in the UK Routine Clinical Practice

Study Overview
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Brief Summary
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This population-based study will identify patients with rapid and irregular heartbeat which is not due to a fault with the heart valves (non-valvular atrial fibrillation) who initiate rivaroxaban, apixaban or warfarin as treatment for Stroke Prevention in Atrial Fibrillation (SPAF). Purpose of the study is to learn more about the safety and how well the drugs rivaroxaban, apixaban and warfarin work in patients appropriately and inappropriately receiving standard and reduced doses of each drug for reducing the risk of stroke in atrial fibrillation. Real world data from routine general practice stored in the primary care database in the UK, The Health Improvement Network (THIN), will be used for investigation.

Detailed Description
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Primary objectives are to assess the safety and effectiveness of rivaroxaban, apixaban and warfarin based on the risk of intracranial hemorrhage and hemorrhagic strokes (safety) and ischemic stroke, systemic embolism and myocardial infarction (effectiveness). Secondary objectives comprise the assessment of the mentioned risks in subpopulations of patients with renal impairment or diabetes, mortality rates, and drug utilisation as well as patient characteristics before and after the first intracranial hemorrhage or ischemic stroke.

Official Title
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Safety and Effectiveness of Rivaroxaban and Apixaban Compared to Warfarin in Non-valvular Atrial Fibrillation Patients in the Routine Clinical Practice in the UK

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Apixaban (Eliquis)
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with non-valvular atrial fibrillation New users of rivaroxaban, apixaban or warfarin At least one year enrollment with the general practice (GP) One year since first health contact recorded in THIN prior to the first prescription of a study drug Exclusion Criteria: Patients with other recent indications of oral anticoagulant initiation Individuals on more than one oral anticoagulant on the start date Users of rivaroxaban apart from 15 / 20 mg daily dose Users of apixaban apart from 5 / 10 mg daily dose

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 |
| --- | --- |
| NVAF-patients_1<br>Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Rivaroxaban at a dose of 15 or 20 mg once daily<br>* Other names: Non-Vitamin K Oral Anticoagulant (NOAC);|
| NVAF-patients_2<br>Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin. | Drug: Apixaban (Eliquis)<br>* Apixaban at a dose of 2.5 or 5 mg twice daily<br>* Other names: Non-Vitamin K Oral Anticoagulant (NOAC);|
| NVAF-patients_3<br>Adult patients with non-valvular atrial fibrillation (NVAF) and one year health records in the British THIN-database, who have not yet used rivaroxaban, apixaban and warfarin. | Drug: Warfarin<br>* Warfarin dose as prescribed by medical practitioner<br>* Other names: Vitamin K Antagonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of intracranial hemorrhage | Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage. | Retrospective analysis of data from 2012 to 2017 | 
| Risk of ischemic events | Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction. | Retrospective analysis of data from 2012 to 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of intracranial hemorrhage in NVAF-patients with renal impairment | Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage. | Retrospective analysis of data from 2012 to 2017 | 
| Risk of ischemic events in NVAF-patients with renal impairment | Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction. | Retrospective analysis of data from 2012 to 2017 | 
| Risk of intracranial hemorrhage in NVAF-patients with diabetes | Intracranial hemorrhage includes intracerebral hemorrhage, subarachnoid hemorrhage, subdural and epidural hemorrhage. | Retrospective analysis of data from 2012 to 2017 | 
| Risk of ischemic events in NVAF-patients with diabetes | Ischemic events include ischaemic stroke / systemic embolism and myocardial infarction. | Retrospective analysis of data from 2012 to 2017 | 
| All-cause mortality | Rate of deaths from all causes. | Retrospective analysis of data from 2012 to 2017 | 
| Drug utilisation | Drug utilisation comprises a descriptive analysis of characteristics of index prescription, time trends and drug discontinuation. | Retrospective analysis of data from 2012 to 2017 | 
| Drug utilisation after first intracranial hemorrhage or ischemic stroke | Drug utilisation comprises a descriptive analysis of characteristics of index prescription, time trends and drug discontinuation. | Retrospective analysis of data from 2012 to 2017 | 
| Patient characteristics | Patient characteristics comprise a descriptive analysis of baseline characteristics, comorbidities, co-medications and time trends. | Retrospective analysis of data from 2012 to 2017 | 
| Patient characteristics after first intracranial hemorrhage or ischemic stroke | Patient characteristics comprise a descriptive analysis of baseline characteristics, comorbidities, co-medications and time trends. | Retrospective analysis of data from 2012 to 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral anticoagulants, Under-dosing, Stroke prevention in atrial fibrillation, Safety, Effectiveness