Effectiveness And Safety Of Oral Anticoagulants Among Obese Patients With Non-Valvular A-Fib In VA Patients With Medicare

Effectiveness and Safety of Oral Anticoagulants Among Obese Patients With Non-Valvular Atrial Fibrillation in the Veterans Affairs Population With Medicare

The overall objective of this analysis is to understand patient characteristics, the use of treatment, and clinical outcomes among obese (overweight) and severely obese patients with non-valvular atrial fibrillation (NVAF) who initiate therapy with OACs (oral anti-coagulants). The aim of this study is to compare all DOACs (direct oral anti-coagulants) to warfarin.

However, the primary analysis will be conducted among apixaban vs warfarin patients only. If sample size permits, we will also conduct other DOAC vs warfarin and DOAC vs DOAC analysis.

Study Overview

• Status: Completed
• Conditions: Obesity; Atrial Fibrillation; Anticoagulants
• Intervention / Treatment: Drug: Apixaban

• Study Type: Observational
• Enrollment (Actual): 107383

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10012
      • Pfizer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Obese or severely obese AF patients in the CMS Medicare and Veterans' Health Affairs (VHA) databases who were newly prescribed OACs between January 1, 2013 and December 31, 2017.

Description

Inclusion Criteria:

• Obese or severely obese.
• Initiated an OAC from July 1, 2013 - December 31, 2017; the first DOAC pharmacy claim date during the identification period will be designated as the index date. The first warfarin prescription date will be designated as the index date for patients without any DOAC claim.
• Individuals ≥18 years old as of the index date.
• Had 6 months continuous health plan enrollment with medical benefits (Parts A & B) for at least 6 months pre-index date (baseline period).
• At least 1 diagnosis of AF prior to or on index date, identified by any medical claim associated with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code of 427.31 or International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code of I480-I482, and I4891.
• Had body weight or BMI value reported within ±6 months of the index date.

Exclusion Criteria:

• Had medical claims indicating a diagnosis or procedure of rheumatic mitral valvular heart disease, heart valve replacement/transplant, venous thromboembolism, or transient AF 6 months prior to or on the index date.
• Had hip/knee replacement surgery within 6 weeks prior to or on the index date.
• Were pregnant during the study period.
• Had an OAC prescription during the 6 months pre-index date.
• Had follow-up time equal to 0 days.
• Had more than one OAC on the index date.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Apixaban Group; The cohort prescribed apixaban and diagnosed with Atrial Fibrillation	Drug: Apixaban; Anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation.; Other Names: Eliquis
Warfarin Group; patients prescribed warfarin only diagnosed with Atrial Fibrillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Obese Participants	Event rate per 100 participant-years for first occurrence of major bleeding (MB) event after index date in obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017 [3.5 years]). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of gastrointestinal (GI), intracranial hemorrhage (ICH), and other sites. MB was equal to 1 if bleeding event was greater than equal to (>=) 1.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Event Rate Per 100 Participant-Years For First Occurrence of Major Bleeding Events After Index Date in Morbidly Obese Participants	Event rate per 100 participant-years for first occurrence of MB event after index date in morbidly obese participants was reported. MB after index date was identified using hospital claims and occurred anytime during the follow-up period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. MB events included the composite of GI, ICH, and other sites. MB was equal to 1 if bleeding event was >=1.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Obese Participants	Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was >=1.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Event Rate Per 100 Participant-Years For First Occurrence of Stroke or Systemic Embolism (SE) Events After Index Date in Morbidly Obese Participants	Event rate per 100 participant-years for first occurrence of stroke or SE events after index date in morbidly obese participants was reported. Stroke/SE were identified using hospital claims and occurred anytime during the period of drug use or within 30 days from the last day of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim. Stroke events included the composite of any ischemic, any hemorrhagic and SE stroke events. Stroke/SE was equal to 1 if stroke event was >=1.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Obese Participants	Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Event Rate Per 100 Participant-Years For First Occurrence of Net Clinical Benefit After Index Date in Morbidly Obese Participants	Event rate per 100 participant-years for first occurrence of net clinical benefit after index date in morbidly obese participants was reported. For participants with stroke/SE or MB event, net clinical benefit was assessed by evaluating the first hospital claim for a stroke/SE or MB event. The hospital claim occurred anytime during the period of drug use or within 30 days from the last day of supply of treatment prescription. Index date was defined as date of first DOAC pharmacy claim date during the identification period (July 1, 2013-December 31, 2017). The first warfarin prescription date was designated as the index date for participants without any DOAC claim.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)
Charlson Comorbidity Index (CCI)	CCI based on various comorbid conditions such as myocardial infarction, CHF, peripheral vascular disease, cerebrovascular disease, dementia, chronic obstructive pulmonary disease, rheumatologic disease, peptic ulcer disease, mild liver disease, diabetes (mild to moderate), diabetes + complications, hemiplegia or paraplegia, renal disease, any malignancy (lymphoma and leukemia), moderate/severe liver disease, metastatic solid tumor, and acquired immune deficiency syndrome (AIDS) were reported. CCI score range was from 0 to 14, where "0"= low comorbid condition and "14"= high comorbid condition, higher scores indicated more comorbidity.	Baseline (6 months prior to index date)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Therapeutic Range (TTR) During Follow-up Period	TTR was computed using INR values among warfarin participants during the follow-up. TTR was calculated based on the percentage of time a participant remained in therapeutic range evaluated during the entire follow-up period. TTR >=65 percent (%) was observed as good and TTR less than (<) 65% was observed as poor.	From first dose of study drug to follow-up period or within 30 days from last prescription date (data collected and observed retrospectively for 3.5 years)

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): November 2, 2020
• Primary Completion (Actual): November 3, 2020
• Study Completion (Actual): November 3, 2020

Study Registration Dates

• First Submitted: December 18, 2020
• First Submitted That Met QC Criteria: December 18, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Stroke; Medicare; Major Bleeding; Veterans Affairs
• 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
• Other Study ID Numbers: B0661162

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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes