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

• Conditions: Frailty; Stroke; Atrial Fibrillation; Anticoagulant-induced Bleeding
• Interventions: Drug: Rivaroxaban; Drug: Dabigatran; Drug: Edoxaban; Drug: Warfarin; Drug: Apixaban

• Registration Number: NCT04878497
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2021-03-30
• Study First Submitted: 2021-04-22
• Status Verified: 2021-05
• Study First Submitted QC: 2021-05-05
• Last Update Submitted: 2021-05-05
• Study First Posted: 2021-05-07
• Last Update Posted: 2021-05-07
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1000000

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Rivaroxaban	Rivaroxaban	New users of rivaroxaban
Dabigatran	Dabigatran	New users of dabigatran
Edoxaban	Edoxaban	New users of edoxaban
Warfarin	Warfarin	New users of warfarin
Apixaban	Apixaban	New users of apixaban

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States