Prospective Monitoring of Non-Vitamin K Oral Anticoagulants in Older Adults With Atrial Fibrillation and Frailty

The objective of this study is to establish a near-real-time prospective monitoring program in Medicare, Optum and MarketScan Research data to evaluate the benefit of new cardiovascular disease (CVD) drugs for older adults with frailty. Prospective monitoring program seeks to find early effectiveness and safety signals of new drugs by updating the analysis at regular intervals as new Medicare data become available. This study specifically aims to emulate a prospective surveillance of the effectiveness and safety of non-vitamin K oral anticoagulants (NOAC) vs. a comparator, warfarin, in older adults with atrial fibrillation and different frailty status. This program will be enhanced by incorporating a novel claims-based frailty index, which has been shown useful in assessing how the benefits and harms of drug therapy vary by frailty.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Atrial Fibrillation; Frailty; Anticoagulant-induced Bleeding
• Intervention / Treatment: Drug: Warfarin; Drug: Dabigatran; Drug: Rivaroxaban; Drug: Apixaban; Drug: Edoxaban

Detailed Description

Data sources of use for this study are: Medicare Database, Optum Database, and MarketScan Research Database. All data from years 2013-2020 (available data may vary depending on the database) will be analyzed in the study.

This study follows a sequential cohort monitoring design. The monitoring analysis will include 1) retrospective analysis of available data (2013-2018) at the time of first analysis (April 2021) and 2) prospective analysis of new data (2019-2020) as they become available to the researchers. Within each database and by frailty status (frail vs non-frail), the investigators will emulate annual updating of data by creating a propensity score (PS)-matched cohort of new users every 1-year interval. Each sequential cohort will be followed for development of the outcomes of interest. At the end of each interval, time-to-event data from all sequential cohorts will be pooled for outcome analysis. The surveillance will be performed by frailty status (frail vs non-frail) at the time of drug initiation.

• Study Type: Observational
• Enrollment (Anticipated): 1000000

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population includes older patients with non-valvular AF who initiates warfarin or a NOAC.

Description

Inclusion Criteria:

• Initiation of a NOAC or warfarin (day 0 is the initiation day)
• Continuous enrollment in medical and drug insurance in [-183, 0] days
• Diagnosis of AF in [-183, 0] days
• CHA2DS2-VASc score ≥2 (moderate or high risk for stroke)
• No prior use of NOAC or warfarin in [-183, -1] days
• No recent hospitalization for stroke or major bleeding in [-60, 0] days
• No recent nursing facility stay in [-60, 0] days

Exclusion Criteria:

• Contraindication to either drug in [-183, 0] days
• Valvular heart disease or mechanical heart valve in [-183, 0] days
• Intracranial or retroperitoneal hemorrhage in [-183, 0] days
• Chronic kidney disease stage V, end-stage renal disease, or dialysis in [-183, 0] days
• Other indications for anticoagulation therapy in [-183, 0] days

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Warfarin; New users of warfarin	Drug: Warfarin; Initiation of warfarin, identified using prescription fill in pharmacy claims
Dabigatran; New users of dabigatran	Drug: Dabigatran; Initiation of dabigatran, identified using prescription fill in pharmacy claims
Rivaroxaban; New users of rivaroxaban	Drug: Rivaroxaban; Initiation of rivaroxaban, identified using prescription fill in pharmacy claims
Apixaban; New users of apixaban	Drug: Apixaban; Initiation of apixaban, identified using prescription fill in pharmacy claims
Edoxaban; New users of edoxaban	Drug: Edoxaban; Initiation of edoxaban, identified using prescription fill in pharmacy claims

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with composite events of stroke or systemic embolism	Stroke OR systemic embolism, identified by relevant diagnoses in the claims data	January 2013 - December 2020 (after drug initiation)
Number of patients with major bleeding	Major bleeding, identified by relevant diagnoses in the claims data	January 2013 - December 2020 (after drug initiation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with all-cause mortality	All-cause mortality is defined by the National Death Index file or vital status information in the claims data.	January 2013 - December 2020 (after drug initiation)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Dae Hyun Kim, MD, MPH, ScD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: April 22, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Frailty; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran; Apixaban; Edoxaban; Warfarin
• Other Study ID Numbers: 2019P000110-NOAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No