Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Practice (Sweden)

Study Overview
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Brief Summary
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This prospective cohort study will provide information about: Characteristics of Rivaroxaban use in patients who are prescribed Rivaroxaban for the first time compared to patients who are prescribed standard of care for the first time. The occurrence of intracranial haemorrhage, gastrointestinal and urogenital bleeding, and the occurrence of non-infective liver disease.

Official Title
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A Pharmacoepidemiological Study of Rivaroxaban Use and Potential Adverse Outcomes in Routine Clinical Practice in Sweden

Conditions
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Acute Coronary Syndrome, Venous Thrombosis, Pulmonary Embolism, Atrial Fibrillation

Intervention / Treatment
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* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Standard of care drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All male and female patients who have filled a prescription for rivaroxaban, warfarin, aspirin, clopidogrel, ticlopidine, prasugrel and ticagrelor in any pharmacy in Sweden, between December 9, 2011 and December 31, 2018 Exclusion Criteria: - For the AF and DVT/PE treatment indications, patients who have filled a prescription for warfarin or another oral anticoagulant at any time between July 1, 2005 and December 9, 2011 will be excluded
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 |
| --- | --- |
| Rivaroxaban / Cohort 1<br>Patients who have filled a prescription for rivaroxaban in any pharmacy in Sweden during the study period. | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Treatment of deep vein thrombosis (DVT) or pulmonary embolism (PE), and prevention of recurrent DVT and PE (15 mg rivaroxaban twice daily [bid] for 3 weeks, then 15 mg or 20 mg once daily [od], tablets). Prevention of stroke and systemic embolism with non-valvular atrial fibrillation (stroke prevention in atrial fibrillation [SPAF]) with one or more risk factors, prior stroke or transient ischaemic attack (20 mg rivaroxaban [od], tablets). Prevention of venous thromboembolism (VTE) in patients undergoing elective hip or knee replacement surgery (recommended dose: 10 mg rivaroxaban [od] tablets for 35 days following hip replacement surgery and 14 days following knee replacement surgery). Co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, for the prevention of atherothrombotic events in patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers (recommended dose 2.5 mg rivaroxaban tablets [bid]).<br>|
| Standard of care drugs / Cohort 2<br>Patients who have filled a prescription for standard of care drugs (warfarin, aspirin, clopidogrel, ticlopidine, prasugrel or ticagrelor) in any pharmacy in Sweden during the study period. | Drug: Standard of care drugs<br>* For DVT/PE treatment and SPAF, standard of care is treatment with the most widely used vitamin K antagonist, phenprocoumon, and for the secondary prevention of ACS, standard of care is antiplatelet drug(s) such as low-dose acetylsalicylic acid, clopidogrel, dipyridamole, prasugrel, ticlopidine and ticagrelor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of demographic and clinical characteristics of patients who are prescribed oral rivaroxaban for the first time in comparison with those who are prescribed standard of care for the first time | The following data will be collected and assessed at 2 and 4 years after rivaroxaban market authorization: • age and sex distribution at index date • dose of rivaroxaban at index date • diagnosis associated with the prescribing of the index drug • use of specific prescribed medications confirming ACS indication • use of other prescribed medications • comorbidity based on diagnoses • renal impairment • healthcare utilization (e.g. outpatient visits and hospital admissions) | up to 4 years | 
| Safety and effectiveness: occurrence of hospitalization for a) intracranial haemorrhage, (b) gastrointestinal bleeding, (c) urogenital bleeding among users of rivaroxaban in comparison with individuals receiving current standard of care | The two cohorts will be followed up from the index date until 12 months after the end of the enrolment period for potential outcomes For descriptive purposes, annualized crude incidence rates of the major bleeding events will be calculated, accompanied by 95% confidence intervals. For evaluation of safety and effectiveness outcome events, Cox proportional hazards regression model will be used. Propensity score matching will be done to account for confounding by indication. | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of hospitalization for bleeding events not specified as primary safety outcomes (other bleeding, secondary safety outcome) in individuals receiving rivaroxaban, in comparison with those receiving current standard of care. | Outcome will be analyzed after end of data collection. Cox proportional hazards regression model will be used. Propensity score matching will be done to account for confounding by indication. | at 5 years | 
| Occurrence of non-infective liver disease (secondary safety outcome) in individuals receiving rivaroxaban in comparison with those receiving current standard of care. | Outcome will be analyzed after end of data collection. Cox proportional hazards regression model will be used. Propensity score matching will be done to account for confounding by indication. | at 5 years | 
| Outcomes related to effectiveness (DVT/PE, ischaemic stroke or myocardial infarction) in individuals receiving rivaroxaban in comparison with those receiving current standard of care. | Outcome will be analyzed after end of data collection. Cox proportional hazards regression model will be used. Propensity score matching will be done to account for confounding by indication. | at 5 years | 
| All-cause mortality as well as cause-specific mortality. | Outcome will be analyzed after end of data collection. Cox proportional hazards regression model will be used. Propensity score matching will be done to account for confounding by indication. | at 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic Uses, Rivaroxaban, Venous Thrombosis/Pulmonary Embolism, Stroke Prevention in Atrial Fibrillation, Anticoagulants, Hematologic Agents, Observational, Pulmonary Embolism, Venous Thrombosis, Venous Thromboembolism, Intracranial Hemorrhages, Gastrointestinal Hemorrhage