Prospective Monitoring of Angiotensin Receptor Neprilysin Inhibitor in Older Adults With Heart Failure and Frailty
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Brigham and Women's Hospital
- Enrollment
- 40,000
- Locations
- 1
- Primary Endpoint
- Number of patients with composite events of death or heart failure hospitalization
Study Overview
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 Angiotensin Receptor Neprilysin Inhibitor(ARNI) vs. a comparator, Angiotensin II Receptor Blockers (ARBs), in older adults with Heart Failure with Reduced Ejection Fraction (HFrEF) 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 2014-2020 will be included in the study.
This study follows a sequential cohort monitoring design. The monitoring analysis will include 1) retrospective analysis of available data (2015-2017) at the time of first analysis (January 2021) and 2) prospective analysis of new data (2018-2020) as they become available to the researchers. Within each database, we will emulate biannual updating of data by creating a propensity score (PS)-matched cohort of new users every 6-month interval, beginning on the first marketing of ARNI (July 7, 2015-December 31, 2015, and 6-month intervals afterwards). Each sequential cohort will be followed for development of the outcomes of interest. Outcome analysis will be performed at a pre-specified 6-month interval (prospective analysis). The surveillance will be performed by frailty status (frail vs non-frail) at the time of drug initiation. The results from each database will be pooled using fixed-effects meta-analysis (assuming low heterogeneity across the databases).
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Continuous enrollment for medical and drug insurance (e.g., Medicare Part A, B, and D) in [-365, 0] days
- •Diagnosis of Heart Failure either two outpatient diagnosis or one inpatient diagnosis in [-365, 0] days
- •Reduced Ejection Fraction < 45% identified using a validated claims-based algorithm in [-365, 0] days
- •Day 0 is the initiation date of the study drug.
Exclusion Criteria
- •No prior use of Angiotensin receptor neprilysin inhibitor or angiotensin II receptor blocker in [-365, -1] days
- •No recent HF hospitalization, defined as HF diagnosis (defined in attached protocol) in the primary position in the inpatient dataset in [-60, 0] days
- •No recent nursing facility stay (defined in attached protocol) for [-60, 0] days
- •Age < 65 years
- •Exposure to both drugs on day 0
- •Contraindication to either drug (exclusion assessment window: [-60, 0] days, unless specified otherwise; algorithms specified in attached protocol)
- •Note: If a patient meets the above-mentioned eligibility criteria more than once, only the first record will be included.
Arms & Interventions
New users of angiotensin receptor neprilysin inhibitor
Intervention: sacubitril/valsartan (Drug)
New users of angiotensin II receptor blockers
Intervention: Angiotensin II Receptor Blockers (Drug)
Outcomes
Primary Outcomes
Number of patients with composite events of death or heart failure hospitalization
Time Frame: July 2015 - December 2020
All-cause mortality OR heart failure hospitalization
Number of patients with composite serious adverse events
Time Frame: July 2015 - December 2020
Hypotension OR acute kidney injury/acute kidney failure OR hyperkalemia OR angioedema
Secondary Outcomes
- Number of patients with heart failure hospitalization(July 2015 - December 2020)
- Number of patients with all-cause mortality(July 2015 - December 2020)
- Number of patients with hypotension(July 2015 - December 2020)
- Number of patients with hyperkalemia(July 2015 - December 2020)
- Number of patients with acute kidney injury/acute kidney failure(July 2015 - December 2020)
- Number of patients with angioedema(July 2015 - December 2020)
Investigators
Dae Hyun Kim, MD, MPH, ScD
Associate Professor
Brigham and Women's Hospital