Clinical and Economic Outcomes of Oral Anticoagulants in Non-valvular Atrial Fibrillation (ARISTOPHANES)

Real-World Comparative Effectiveness Research and Related Economic Outcomes Among Nonvalvular Atrial Fibrillation Patients Using Oral Anti-coagulants

The primary objectives of this study are to compare the risk of major bleeding and stroke/systemic embolism (SE) events among oral anticoagulant (OAC)-naïve non-valvular atrial fibrillation (NVAF) patients initiating OAC warfarin or apixaban or dabigatran or rivaroxaban treatment.

Study Overview

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

• Study Type: Observational
• Enrollment (Actual): 466991

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Local Institution

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

NVAF patients who were initiators of warfarin or apixaban or dabigatran or rivaroxaban treatment from 01-Jan-2013 through 30-Sep-2015. All patients who have at least 1 year of baseline data available and no prior OAC use will be included in this study.

Description

Inclusion Criteria:

1. Had 1 or more pharmacy claim for apixaban or warfarin or dabigatran or rivaroxaban during the identification period (01-Jan-2013 to 30-Sep-2015). The first OAC pharmacy claim date during the identification period will be designated as the index date
2. Patients 18 years old or older as of the index date
3. At least 1 diagnosis of atrial fibrillation prior to or on index date, identified by any medical claim
4. At least 12 months of baseline period prior to index date with continuous enrollment

Exclusion Criteria:

1. Evidence of valvular heart disease, transient atrial fibrillation, venous thromboembolism during the 12-month baseline period or on the index date
2. Evidence of pregnancy during the study period
3. Had a pharmacy claim for warfarin, apixaban, dabigatran, rivaroxaban, or edoxaban during the 12-month baseline period
4. Had more than 1 oral anticoagulant claim on the index date

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
NVAF patients on Warfarin; NVAF patients newly initiated with Warfarin. Non-Interventional.
NVAF patients on Apixaban; NVAF patients newly initiated on Apixaban. Non-Interventional.
NVAF patients on Dabigatran; NVAF patients newly initiated with Dabigatran. Non-Interventional.
NVAF patients on Rivaroxaban; NVAF patients newly initiated with Rivaroxaban. Non-Interventional.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to first major bleeding event	Up to 33 months
Time to first stroke/systemic embolism (SE) event	Up to 33 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Major bleeding-related medical costs	Up to 33 months
Stroke/SE-related medical costs	Up to 33 months
All-cause Healthcare costs	Up to 33 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Lip GYH, Keshishian AV, Kang AL, Li X, Dhamane AD, Luo X, Balachander N, Rosenblatt L, Mardekian J, Nadkarni A, Pan X, Di Fusco M, Garcia Reeves AB, Yuce H, Deitelzweig SB. Effectiveness and Safety of Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Diabetes Mellitus. Mayo Clin Proc. 2020 May;95(5):929-943. doi: 10.1016/j.mayocp.2019.05.032.
• Li X, Keshishian A, Hamilton M, Horblyuk R, Gupta K, Luo X, Mardekian J, Friend K, Nadkarni A, Pan X, Lip GYH, Deitelzweig S. Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach. PLoS One. 2018 Jan 26;13(1):e0191722. doi: 10.1371/journal.pone.0191722. eCollection 2018.
• Lip GYH, Keshishian A, Li X, Hamilton M, Masseria C, Gupta K, Luo X, Mardekian J, Friend K, Nadkarni A, Pan X, Baser O, Deitelzweig S. Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients. Stroke. 2018 Dec;49(12):2933-2944. doi: 10.1161/STROKEAHA.118.020232.

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• Investigator Inquiry Form

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): February 26, 2023
• Study Completion (Actual): March 8, 2023

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: CV185-543