Safety and Effectiveness of Apixaban Compared to Warfarin in Patients With Non-valvular Atrial Fibrillation (a Type of Irregular Heart Rhythm) at Higher Chance of Bleeding

Safety and Effectiveness of Apixaban Compared to Warfarin in NVAF Patients at Higher Risk of Bleeding.

• The purpose of this study is to compare effectiveness and safety of warfarin and apixaban among non-valvular atrial fibrillation (NVAF) patients at higher chance of bleeding using a Japanese nation-wide administrative claims database.
• Atrial fibrillation (AF) is characterized by a fast, irregular heartbeat which can cause blood to pool in the atria and increase the chance of the formation of blood clots.
• An anticoagulation therapy is a critical treatment to prevent thromboembolism in NVAF patients.
• Apixaban was demonstrated superiority compared to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality in patients with AF in Phase 3 clinical trial.
• Previously we have shown that bleeding risks as well as stroke/SE risks are less in real world clinical practice in Japan compared to warfarin. However there are limited apixaban data for Japanese NVAF patients with high bleeding risk(s).
• This study will evaluate the risk of stroke/systemic embolism as well as the risk of bleeding in the real world settings in Japanese patients with NVAF who has higher chance of bleeding

Study Overview

• Status: Completed
• Conditions: Non-valvular Atrial Fibrillation

• Study Type: Observational
• Enrollment (Actual): 120722

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Pfizer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study uses data from the MDV database, which includes the data used for both inpatient and outpatient insurance claims by hospitals according to the Diagnosis Procedure Combination (DPC) procedure.

The study population will consist of adults with NVAF who are newly prescribed apixaban or warfarin.

Description

Inclusion Criteria:

• Diagnosed with atrial fibrillation (AF) anytime in the baseline period or on the index date, also have definitive diagnosis of AF anytime in the baseline period, on the index date, or post-index period.
• Prescribed apixaban or warfarin on or after the day of AF diagnosis. The first observed prescription will be used to identify the patient's index date and treatment cohort
• No use of the any oral anticoagulants (OACs) during the baseline period (the 180 days before the index date)
• Age of 18 years or older on the index date

Exclusion Criteria:

• Having a diagnosis of valvular atrial fibrillation, post-operative atrial fibrillation, rheumatic atrial fibrillation or mechanical-valvular atrial fibrillation during the baseline and post-index period
• Having a procedure of prosthetic heart valve during the baseline period
• Having a cardiac surgery procedure record during the baseline period
• Having a diagnosis of venous thromboembolism during the baseline period
• Having a hemodialysis during the baseline period
• Female patients with pregnancy during the baseline and follow-up period
• Patients prescribed apixaban other than approved daily dose (<5 mg or >10 mg)
• Patients prescribed OACs during baseline period

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate Per 1000 Participant-Years For First Occurrence of Composite Stroke and Systemic Embolism (SE) Events After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of composite stroke and SE events after index date was reported. Stroke events included the composite of any ischemic and any hemorrhagic stroke events (excluding non-traumatic extradural hemorrhage). Stroke after index date not including the index date was identified using hospital claims which had a stroke diagnosis code as the first listed International Classification of Diseases 10th Revision (ICD-10) diagnosis code. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Bleeding Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of major bleeding event after index date was reported. Major bleeding was defined as any bleeding that required hospitalization for treatment. Major bleeding after index date was identified using hospital claims which had a bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate Per 1000 Participant-Years For First Occurrence of Ischemic Stroke Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. Ischemic stroke after index date not including the index date was identified using hospital claims which had an ischemic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Incidence Rate Per 1000 Participant-Years For First Occurrence of Hemorrhagic Stroke Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of hemorrhagic stroke event after index date was reported. Hemorrhagic stroke after index date not including the index date was identified using hospital claims which had a hemorrhagic stroke diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Incidence Rate Per 1000 Participant-Years For First Occurrence of Systemic Embolism (SE) Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of SE event after index date was reported. SE after index date not including the index date was identified using hospital claims which had a SE diagnosis code as the first listed ICD-10 diagnosis code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Intracranial Bleeding Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of major intracranial bleeding event after index date was reported. Major intracranial bleeding after index date was identified using hospital claims which had an intracranial bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study
Incidence Rate Per 1000 Participant-Years For First Occurrence of Major Gastrointestinal (GI) Bleeding Event After Index Date: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. Any GI bleeding after index date was identified using hospital claims which had a GI bleeding diagnosis code as the first listed ICD-10 or disease code. Index date: date when participants initiated warfarin or apixaban. Follow-up period: from next day of the index date till occurrence of target outcome event, discontinuation of apixaban or warfarin; switching from apixaban or warfarin; withdrawal from the database, whichever occurred first.	Follow-up period during data observation period from Mar 2011 to Jun 2021 (approximately 10 years 4 months); extracted data evaluated in approximately 1 month of this study

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2022
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: B0661178

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.