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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Atrial Fibrillation, Frailty, Anticoagulant-induced Bleeding, Stroke

Intervention / Treatment
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* Drug: Warfarin
* Drug: Dabigatran
* Drug: Rivaroxaban
* Drug: Apixaban
* Drug: Edoxaban


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Warfarin<br>New users of warfarin | Drug: Warfarin<br>* Initiation of warfarin, identified using prescription fill in pharmacy claims<br>|
| Dabigatran<br>New users of dabigatran | Drug: Dabigatran<br>* Initiation of dabigatran, identified using prescription fill in pharmacy claims<br>|
| Rivaroxaban<br>New users of rivaroxaban | Drug: Rivaroxaban<br>* Initiation of rivaroxaban, identified using prescription fill in pharmacy claims<br>|
| Apixaban<br>New users of apixaban | Drug: Apixaban<br>* Initiation of apixaban, identified using prescription fill in pharmacy claims<br>|
| Edoxaban<br>New users of edoxaban | Drug: Edoxaban<br>* Initiation of edoxaban, identified using prescription fill in pharmacy claims<br>|

What is the study measuring?
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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) |