Benefit-Risk Of Arterial THrombotic prEvention With Rivaroxaban for Atrial Fibrillation in France

Study Overview
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Brief Summary
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The purpose of the study is to compare the one-year and two-year risk of each of the following individual outcomes: Stroke and systemic embolism (SE), major bleeding and death between new users of anticoagulant for Stroke prevention in atrial fibrillation (SPAF) during drug exposure: rivaroxaban versus Vitamin K antagonists (VKA), and rivaroxaban versus dabigatran

Detailed Description
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Main objective: To compare the one-year and two-year risk of each of the following individual outcomes: Stroke and systemic embolism (SE), major bleeding and death between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran. Secondary objectives: To describe the drug exposure to rivaroxaban, dabigatran, and VKA for SPAF in new users, as well as and pattern of use; To compare the one-year and two-year risk of the following individual outcomes: a composite of stroke and SE, major bleeding and death, clinically relevant bleeding (CRB) and acute coronary syndrome (ACS) between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran; To estimate the cumulative incidence and the incidence rate of each individual main and secondary outcome (stroke and SE, major bleeding, CRB, death, composite criteria, and ACS), as well as according to individual diagnose of each of these outcomes, during drug exposure for rivaroxaban, dabigatran, and VKA; To estimate the cumulative incidence of each individual main and secondary outcome (stroke and SE, major bleeding, CRB, death, composite criteria, and ACS), as well as according individual diagnose of each of these outcomes during post-anticoagulant exposure for rivaroxaban, dabigatran, and VKA (i.e. after anticoagulant discontinuation); To assess outcome risk factors, including (but not limited to), gender, age, stroke and bleeding risk scores (CHA2DS2-VASc and HAS-BLED), low or high dosage at index date for DOAC, drug predisposing to bleeding during drug exposure and significant baseline characteristics; To describe and compare healthcare resources utilisation related to SPAF during rivaroxaban, dabigatran, and VKA exposure, including outcomes, and their related costs from the societal perspective and from the French healthcare insurance perspective.

Official Title
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Benefit-Risk Of Arterial THrombotic prEvention With Rivaroxaban for Atrial Fibrillation in Daily Clinical Practice - A French Cohort Within the Nationwide Claims and Hospital Database

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Vitamin K antagonists
* Drug: dabigatran (Pradaxa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite non-valvular atrial fibrillation: A first reimbursed dispensation of rivaroxaban, dabigatran, or VKA in 2013 or 2014, and No previous DOAC (rivaroxaban, dabigatran, apixaban) or VKA dispensation during the previous three years, Definite AF information in the database Probable non-valvular atrial fibrillation:- A first reimbursed dispensation of rivaroxaban, dabigatran, or VKA in 2013 or 2014, and No previous DOAC (rivaroxaban, dabigatran, apixaban) or VKA dispensation during the previous three years, Probable AF information in the database (using the development of an AF disease score, see variables definition below), Exclusion Criteria: Patients with Rheumatic valve disease Patients with valve replacement Patients treated with anticoagulants for venous thromboemboslim or prevention of venous thromboembolism after orthopedic surgery

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 99 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 |
| --- | --- |
| Group 1<br>Adult patients with nonvalvular atrial fibrillation (NVAF) treated with rivaroxaban | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Tablets, 20mg once daily<br>|
| Group 2<br>Adult patients with nonvalvular atrial fibrillation (NVAF) treated with vitamin k anatognists | Drug: Vitamin K antagonists<br>* Tablets, dose is based on International Normalized Ratio<br>|
| Group 3<br>Adult patients with nonvalvular atrial fibrillation (NVAF) treated with dabigatran | Drug: dabigatran (Pradaxa)<br>* Tablets, 150 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke and systemic embolism (Effectiveness outcome) | Hospitalization with ischemic or undefined stroke or other systemic arterial embolism or surgical procedure for systemic arterial embolism To compare one year and two year risk between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran. | One year and Two Year | 
| Major Bleeding | Hospitalization with haemorrhagic stroke, other critical organ or site bleeding (intraspinal, intraocular,retroperitoneal, intraarticular or pericardial, or intramuscular), Other bleeding with a transfusion during hospital stay, or resulting in death. To compare one year and two year risk between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran. | One year and Two Year | 
| Death | All-cause death. To compare one year and two year risk between new users of anticoagulant for SPAF during drug exposure: rivaroxaban versus VKA, and rivaroxaban versus dabigatran. | One year and Two Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pattern of use (Exposure, Adherence, Discontinuation, Switch) | To describe the drug exposure to rivaroxaban, dabigatran, and VKA for SPAF in new users and pattern of use | Up to two years | 
| A composite of stroke and SE, major bleeding and death, clinically relevant bleeding and acute coronary syndrome | To compare one year and two year risk between new users of anticoagulant for SPAF during drug exposure: rivaroxaban vs VKA, and rivaroxaban vs dabigatran | One year and Two Year | 
| Cumulative incidence and incidence rate of stroke and SE, major bleeding, clinically relevant bleeding, death, composite criteria, and acute coronary syndrome as well as according individual diagnose of each of these outcomes | During drug exposure for rivaroxaban, dabigatran, and VKA | Up to two years | 
| Cumulative incidence of Stroke and SE, major bleeding, clinically relevant bleeding, death, composite criteria, and acute coronary syndrome as well as according individual diagnose of each of these outcomes | Post-anticoagulant exposure for rivaroxaban, dabigatran, and VKA (i.e. after anticoagulant discontinuation) | Up to two years | 
| Healthcare resources utilisation | Healthcare resources use will be described from reimbursed claims and hospitalisation information Healthcare resources cost will be estimated using the French HAS methodological guide for economic evaluations (2011) | Up to two years |