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

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04878497

Collaborator

(none)

1,000,000

Enrollment

Location

21.1

Anticipated Duration (Months)

47484.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Frailty Anticoagulant-induced Bleeding Stroke	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 Design

Study Type:

Observational

Anticipated Enrollment :

1000000 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

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

Actual Study Start Date :

Mar 30, 2021

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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