Safety and Effectiveness of Apixaban in Very Elderly Patients With Non-valvular Atrial Fibrillation (NVAF) Compared to Warfarin Using Administrative Claims Data

Safety and Effectiveness of Apixaban in Very Elderly Patients With NVAF Compared to Warfarin Using Administrative Claims Data

The objective of this study is to investigate safety and effectiveness of apixaban compared to warfarin in very elderly patients with Non-valvular atrial fibrillation (NVAF). In addition to the absolute age, effects on higher age-related risk factors on relative risk of apixaban to warfarin is also investigated through subgroup analyses.

Study Overview

• Status: Completed
• Conditions: Non-valvular Atrial Fibrillation
• Intervention / Treatment: Drug: Warfarin; Drug: Apixaban

Detailed Description

This is a retrospective non-intervention observational study to evaluate the difference in safety and effectiveness between apixaban and warfarin using a database provided by Medical Data Vision Co. Ltd. (MDV Co. Ltd.). Eligible patients will be extracted from the database and allocated to the pre-defined cohorts based on the actual age, age of NVAF diagnosis and types of anticoagulant therapy.

Patient characteristics will be balanced by an Inverse probability of treatment weighting (IPTW) method, and risk of stroke/SE (primary effectiveness endpoint) and major bleeding (primary safety endpoint) will be compared.

• Study Type: Observational
• Enrollment (Actual): 77814

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan
    • Pfizer Site

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients aged 80 years or older who are newly diagnosed with non-valvular atrial fibrillation (NVAF) and initiate anticoagulation therapy with warfarin or apixaban.

Description

Inclusion Criteria:

• Patients must meet all the following inclusion criteria to be eligible for inclusion in the study.

  1. 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.
  2. 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
  3. No use of the any Oral anticoagulants (OAC)s during the baseline period (the 180 days before the index date)
  4. Age of 18 years or older on the index date.
  5. Index date is at age 80 or older

Exclusion Criteria:

• Patients meeting any of the following criteria will not be included in the study:

  1. 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
  2. Having a cardiac surgery procedure record during the baseline period
  3. Having a joint replacement procedure record during the baseline period
  4. Having a procedure of prosthetic heart valve during the baseline period
  5. Having a diagnosis of venous thromboembolism during the baseline period
  6. Female patients with pregnancy during the follow-up period
  7. Patients prescribed "off-label" doses of OACs (per Japanese package insert of each OAC) or patients treated with OAC but in "off-label" or "contraindicated" manners.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Warfarin cohort (Reference); Patients with NVAF treated with warfarin	Drug: Warfarin; This is observational study and the patients in the warfarin cohort include those who are exposed to warfarin in the real world settings.
Apixaban cohort; Patients with NVAF treated with apixaban	Drug: Apixaban; This is observational study and the patients in the apixaban cohort include those who are exposed to apixaban in the real world settings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate (Per 1,000 Participant-Year) of Composite of Stroke and Systemic Embolism (SE): 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 ischemic and hemorrhagic stroke. International Classification of Diseases 10th Revision (ICD-10) diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Incidence Rate (Per 1,000 Participant-Year) of Major Bleeding: 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. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from the warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate (Per 1,000 Participant-Year) of Cardiogenic Cerebral Embolism: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of cardiogenic cerebral embolism events after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Incidence Rate (Per 1,000 Participant-Year) of Ischemic Stroke (Cerebral Infarction): Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of ischemic stroke event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Incidence Rate (Per 1,000 Participant-Year) of Intracranial Hemorrhage: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of intracranial hemorrhage event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Incidence Rate (Per 1,000 Participant-Year) of Gastrointestinal Bleeding: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of major GI bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months of this study
Incidence Rate (Per 1,000 Participant-Year) of Intraocular Bleeding: Balanced Cohorts	Incidence rate per 1000 participant-years for the first occurrence of intraocular bleeding event after index date was reported. ICD-10 diagnosis code was used to label the events. Index date was defined as a date when participants initiated warfarin or apixaban. Follow-up period: the next day of the index date till occurrence of target outcome, discontinuation of the warfarin or apixaban, switching from warfarin or apixaban, withdrawal from the database, whichever observed first.	Follow-up period during data observation period from 26-Feb-2013 to 31-Dec-2021 (approximately 8 years 10 months); extracted data evaluated in approximately 3.5 months 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): July 1, 2022
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): October 19, 2022

Study Registration Dates

• First Submitted: June 25, 2022
• First Submitted That Met QC Criteria: June 25, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Warfarin; Apixaban
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban; Warfarin
• Other Study ID Numbers: B0661181

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.