Heart Failure, Systolic, Frailty
Conditions
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).
Interventions
DRUGsacubitril/valsartan
Initiation of sacubitril/valsartan, identified using prescription fill in pharmacy claims
Initiation of ARBs, identified using prescription fill in pharmacy claims
Sponsors
Brigham and Women's Hospital
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with composite events of death or heart failure hospitalization | July 2015 - December 2020 | All-cause mortality OR heart failure hospitalization |
| Number of patients with composite serious adverse events | July 2015 - December 2020 | Hypotension OR acute kidney injury/acute kidney failure OR hyperkalemia OR angioedema |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with hypotension | July 2015 - December 2020 | Hypotension is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position. |
| Number of patients with hyperkalemia | July 2015 - December 2020 | Hyperkalemia is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position. |
| Number of patients with all-cause mortality | July 2015 - December 2020 | All-cause mortality is defined by the National Death Index file or vital status information in the claims dataset. |
| Number of patients with angioedema | July 2015 - December 2020 | Angioedema is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position. |
| Number of patients with acute kidney injury/acute kidney failure | July 2015 - December 2020 | Acute kidney injury/Acute kidney failure is defined as any hospitalization or Emergency Department visit with relevant diagnosis codes in the primary position. |
| Number of patients with heart failure hospitalization | July 2015 - December 2020 | Heart failure hospitalization is defined as any hospitalization with relevant diagnosis codes in the primary position. |
Countries
United States
Outcome results
None listed