This cross-sectional study evaluates the changes in angiotensin receptor-neprilysin inhibitor (ARNI) prescribing patterns since US Food and Drug Administration approval in hospitalized patients with heart failure with reduced ejection fraction (HFrEF).
Key Points
Question
How has angiotensin receptor-neprilysin inhibitor (ARNI) prescription changed since US Food and Drug Administration (FDA) drug approval of sacubitril-valsartan?
Findings
This cross-sectional study including 114 333 patients demonstrated that rates of ARNI prescription at discharge have increased from 1.1% during the July 7, 2015, to September 30, 2015, period to 55.4% during the October 1, 2022, to December 31, 2022, period with increased odds of ARNI prescription in time periods after publication of the Comparison of Sacubitril-Valsartan vs Enalapril on Effect on N-Terminal Pro–Brain Natriuretic Peptide in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF) trial and the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment compared with the period immediately after FDA approval of sacubitril-valsartan. Rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) prescription decreased over the same time period.
Meaning
Results suggest that ARNI discharge prescription has increased, and ACEI or ARB prescription has decreased, in the 7 years after FDA approval of sacubitril-valsartan.
Abstract
Importance
Angiotensin receptor-neprilysin inhibition (ARNI) improves mortality among patients with heart failure with reduced ejection fraction (HFrEF), ie, those with an EF of 40% or less.
Objective
To describe national longitudinal trends in ARNI prescribing patterns among hospitalized patients with HFrEF.
Design, Setting, and Participants
Using data from the Get With The Guidelines–Heart Failure (GWTG-HF) registry, hospitalized patients with HFrEF at 614 participating hospitals were identified. Rates of ARNI, angiotensin converting enzyme inhibitor (ACEI), and angiotensin II receptor blocker (ARB) prescription at discharge were evaluated across 3 time periods. Adjusted logistic regression and piecewise logistic regression were used to evaluate the impact of publication dates on ARNI prescription rates.
Exposures
ARNI prescribing patterns in hospitalized patients with HFrEF.
Main Outcomes and Measures
Rates of ARNI, ACEI, and ARB prescription at discharge were evaluated across 3 time periods as follows: (1) period 1 included the US Food and Drug Administration (FDA) approval of sacubitril-valsartan to the day before the PIONEER-HF (Comparison of Sacubitril-Valsartan vs Enalapril on Effect on N-Terminal Pro–Brain Natriuretic Peptide in Patients Stabilized From an Acute Heart Failure Episode) trial publication (July 7, 2015-November 10, 2018); (2) period 2 included the day of the PIONEER-HF trial publication to the day before publication of the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment (November 11, 2018-January 10, 2021); and (3) period 3 included the day of the 2021 update publication to the last available data at the time of analysis (January 11, 2021-December 31, 2022).
Results
A total of 114 333 hospitalized patients (mean [IQR] age, 67.0 [57.0-78.0] years; 74 765 male [65.4%]) were included in this study. Rates of ARNI prescribed at discharge increased from 1.1% (27 of 2451) during July 7, 2015, to September 30, 2015, to 55.4% (1957 of 3536) during October 1, 2022, to December 31, 2022. ACEI or ARB prescription at discharge fell from 88.3% (2612 of 2957) to 45.9% (2033 of 4434) over the same period, whereas ACEI, ARB, or ARNI prescription increased from 71.1% (2639 of 3713) to 84.7% (3990 of 4711). In adjusted logistic regression models, compared with period 1, patients discharged during period 2 and period 3 were found to have a 3.81-fold (95% CI, 3.65-3.98) and 9.15-fold (95% CI, 8.79-9.52) increased odds of ARNI prescription at discharge, and a 0.46 (95% CI, 0.45-0.48) and 0.25 (95% CI, 0.24-0.26) decreased odds of ACEI or ARB prescription at discharge.
Conclusions and Relevance
Results of this cross-sectional study reveal that in the 7 years after FDA drug approval of sacubitril-valsartan, rates of ARNI or ACEI, ARB, or ARNI prescription at discharge increased, and rates of ACEI or ARB prescription decreased. Overall prescription of ARNI at discharge was 55.4% in eligible patients at the end of the study, suggesting remaining opportunity for continued improvement in ARNI prescription.
Introduction
No publication to date, to our knowledge, has temporally followed the prescription patterns of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and angiotensin receptor-neprilysin inhibitors (ARNIs) over time in a large national registry in the US. Here, we sought to fill this gap by evaluating the prescription patterns of ACEI, ARB, and ARNI over time from US Food and Drug Administration (FDA) approval of sacubitril-valsartan to the current day. We also evaluated the potential impact of landmark trials and consensus pathway publication dates on ACEI, ARB, and ARNI prescriptions.
Methods
The study population included adult patients (age ≥18) hospitalized with heart failure with reduced ejection fraction (HFrEF), with an EF of 40% or less. Participants were identified from The American Heart Association’s Get With The Guidelines–Heart Failure (GWTG-HF) registry (eMethods in Supplement 1). GWTG-HF hospitals either enrolled patients without consent under the common rule or the study was considered exempt by their institutional review boards (IRB). The IRB of the American Heart Association, Advarra, offered exemption for the current study. Patients with no recorded medication data and those who died during hospitalization were excluded. Patients with contraindications to ACEI, ARB, or ARNI were excluded from analyses involving those particular drug classes. Participants self-identified with the following races and ethnicities: American Indian or Alaska Native, Asian, Black or African American, Hispanic, Native Hawaiian or Other Pacific Islander, White, or other, which included patients who did not state their race or for whom a race was unable to be determined using existing documentation. Race and ethnicity were included in the analysis given the potential for these variables to impact study outcomes. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.
The study was divided into 3 prespecified time periods. The first spanned from the date of FDA approval of sacubitril-valsartan to the day immediately before the ePublication of the PIONEER-HF trial (Comparison of Sacubitril-Valsartan vs Enalapril on Effect on N-terminal B-type Natriuretic Peptide [NT-proBNP] in Patients Stabilized From an Acute Heart Failure Episode) from July 7, 2015, to November 10, 2018. The second period included the date of ePublication of the PIONEER-HF trial to the day before ePublication of the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment (November 11, 2018-January 10, 2021). The last period extended from the date of ePublication of the 2021 Update to the last available data available in the GWTG-HF database at the time data were extracted for this analysis (January 11, 2021- December 31, 2022).
Statistical Analysis
Baseline characteristics were compared between the 3 groups using Wilcoxon rank-sum and χ2 tests for continuous and categorical variables, respectively. Rates of ARNI prescription at discharge, ARNI initiation at discharge among patients who were not taking an ARNI before admission, ACEI or ARB prescription at discharge, and ACEI, ARB, or ARNI prescription at discharge were calculated in 3-month increments from July 7, 2015, to December 31, 2022. These rates were also compared across the 3 time periods previously described.
Logistic regression models were created to evaluate the association of time period with rates of ACEI, ARB, or ARNI prescription. Additional models were created to evaluate the impact of hospital characteristics on drug prescription. Models were adjusted for prespecified covariates (eMethods in Supplement 1). We next used adjusted piecewise logistic regression to evaluate predicted probabilities of ACEI, ARB, and ARNI prescription over the 3 main time periods previously described. The slope of the logistic regression function was compared in each time period to the time period immediately before it to determine if rates of prescription significantly increased or decreased beyond what would be expected had the trend in the prior time period continued forward. Statistical significance was defined as a 2-sided P value of <.05. SAS (SAS Institute) on the American Heart Association's Precision Medicine Platform was used for the statistical analyses.
Results
The overall cohort consisted of 114 333 patients with HFrEF (mean [IQR] age, 67.0 [57.0-78.0] years; 39 523 female [34.6%]; 74 765 male [65.4%]) who were hospitalized between July 7, 2015, and December 31, 2022, from 614 different hospitals across the US. Patient characteristics stratified by time are shown in the Table, with missingness rates shown in eTable 1 in Supplement 1. Patients self-identified with the following races and ethnicities: 623 American Indian or Alaska Native (0.5%), 2147 Asian (1.9%), 31 789 Black or African American (27.8%), 11 011 Hispanic (9.6%), 639 Native Hawaiian or Other Pacific Islander (0.6%), 72 393 White (63.3%), and 6728 other (5.9%).
Table. Baseline Characteristics of the ARNI Cohort Stratified by Time Period.
| Demographics | Overall cohort: July 7, 2015-December 31, 2022 (N = 114 333) | Time period | P valuea | ||
|---|---|---|---|---|---|
| July 7, 2015-November 10, 2018 (n = 40 178) | November 11, 2018-January 10, 2021 (n = 29 864) | January 11, 2021-December 31, 2022 (n = 44 291) | |||
| Age, median (IQR), y | 67.0 (57.0-78.0) | 68.0 (57.0-80.0) | 68.0 (58.0-78.0) | 66.0 (56.0-77.0) | <.001 |
| Sex, No. (%) | |||||
| Female | 39 523 (34.6) | 14 157 (35.3) | 10 292 (34.5) | 15 074 (34.0) | <.001 |
| Male | 74 765 (65.4) | 25 991 (64.7) | 19 566 (65.5) | 29 208 (66.0) | |
| Body mass index,b median (IQR) | 28.9 (24.6-34.6) | 28.6 (24.4-34.3) | 28.9 (24.6-34.5) | 29.3 (24.9-35.0) | <.001 |
| Race, No. (%) | |||||
| American Indian or Alaska Native | 623 (0.5) | 166 (0.4) | 153 (0.5) | 304 (0.7) | <.001 |
| Asian | 2147 (1.9) | 589 (1.5) | 559 (1.9) | 999 (2.3) | |
| Black or African American | 31 789 (27.8) | 10 848 (27.0) | 8219 (27.5) | 12 722 (28.7) | |
| Native Hawaiian or Other Pacific Islander | 639 (0.6) | 127 (0.3) | 151 (0.5) | 361 (0.8) | |
| White | 72 393 (63.3) | 26 415 (65.8) | 19 291 (64.6) | 26 687 (60.3) | |
| Otherc | 6728 (5.9) | 2029 (5.1) | 1488 (5.0) | 3211 (7.3) | |
| Ethnicity, No. (%) | |||||
| Hispanic | 11 011 (9.6) | 3813 (9.5) | 2773 (9.3) | 4425 (10.0) | .003 |
| Payment source, No. (%) | |||||
| Medicare | 23 580 (49.5) | NA | 4938 (50.9) | 18 642 (49.1) | <.001 |
| Medicaid | 8815 (18.5) | NA | 1614 (16.6) | 7201 (19.0) | |
| Private/health maintenance organization/preferred provider organization/other | 11 282 (23.7) | NA | 2323 (24.0) | 8959 (23.6) | |
| Veterans Affairs/CHAMP/Tricare | 1380 (2.9) | NA | 249 (2.6) | 1131 (3.0) | |
| Self-pay/no insurance | 2097 (4.4) | NA | 426 (4.4) | 1671 (4.4) | |
| Not documented | 503 (1.1) | NA | 148 (1.5) | 355 (0.9) | |
| Medical comorbidities | |||||
| Anemia, No. (%) | 21 997 (19.3) | 7238 (18.0) | 6306 (21.1) | 8453 (19.1) | <.001 |
| Atrial fibrillation/flutter, No. (%) | 39 775 (34.8) | 14 090 (35.1) | 10 750 (36.0) | 14 935 (33.8) | <.001 |
| Cerebrovascular accident/transient ischemic attack, No. (%) | 18 228 (16.0) | 6516 (16.2) | 4792 (16.1) | 6920 (15.6) | .06 |
| Chronic kidney disease (serum creatine >2.0 mg/dL), No. (%) | 20 334 (17.8) | 7085 (17.6) | 5772 (19.3) | 7476 (16.9) | <.001 |
| Chronic kidney disease on dialysis, No. (%) | 3391 (3.0) | 1068 (2.7) | 996 (3.3) | 1327 (3.0) | <.001 |
| Chronic obstructive pulmonary disease/asthma, No. (%) | 36 716 (32.1) | 13 246 (33.0) | 9833 (32.9) | 13 637 (37.1) | <.001 |
| Coronary artery disease, No. (%) | 57 157 (50.0) | 20 701 (51.5) | 15 409 (51.6) | 21 047 (47.6) | <.001 |
| Depression, No. (%) | 18 370 (16.1) | 6030 (15.0) | 5206 (17.4) | 7134 (16.1) | <.001 |
| Diabetes, No. (%) | 54 708 (47.9) | 17 506 (43.6) | 15 439 (51.7) | 21 763 (49.2) | <.001 |
| Hyperlipidemia, No. (%) | 64 791 (56.7) | 21 650 (53.9) | 17 590 (58.9) | 25 551 (57.7) | <.001 |
| Hypertension, No. (%) | 94 430 (82.6) | 33 173 (82.6) | 24 763 (82.9) | 36 494 (82.5) | .24 |
| Peripheral vascular disease, No. (%) | 12 400 (10.9) | 4332 (10.8) | 3376 (11.3) | 4692 (10.6) | .01 |
| Prior myocardial infarction, No. (%) | 29 897 (26.2) | 11 270 (28.1) | 8010 (26.8) | 10 617 (24.0) | <.001 |
| Smoking in last 12 mo, No. (%) | 28 229 (24.7) | 9710 (24.2) | 7085 (23.7) | 11 434 (25.8) | <.001 |
| Sleep disordered breathing, No. (%) | 13 765 (12.0) | 1010 (2.5) | 5207 (17.4) | 7548 (17.1) | <.001 |
| Valvular heart disease, No. (%) | 18 650 (16.3) | 6681 (16.6) | 5049 (16.9) | 6920 (15.6) | <.001 |
| Medical devices/prior procedures | |||||
| Coronary artery bypass graft, No. (%) | 20 363 (17.8) | 8064 (20.1) | 5588 (18.7) | 6711 (15.2) | <.001 |
| CardioMEMS,d No. (%) | 385 (0.3) | 75 (0.2) | 122 (0.4) | 188 (0.4) | <.001 |
| Implantable cardioverter defibrillator/pacemaker/cardiac resynchronization therapy-defibrillator or pacemaker, No. (%) | 37 384 (32.7) | 14 169 (35.3) | 10 005 (33.5) | 13 210 (29.9) | <.001 |
| Percutaneous coronary intervention, No. (%) | 25 466 (22.3) | 8762 (21.8) | 7016 (23.5) | 9688 (21.9) | <.001 |
| ARNI discharge prescription | |||||
| ARNI prescribed at discharge, No. (%) | 32 928 (28.8) | 3638 (9.1) | 8245 (27.6) | 21 045 (47.5) | <.001 |
| ARNI initiated at discharge (among those not on at admission), No. (%) | 17 812/93 971 (19.0) | 2033 (5.3) | 3733 (16.5) | 12 046 (36.6) | <.001 |
| Hospital characteristics | |||||
| Bed size, median (IQR) | 411 (295.0-617.0) | 427.0 (306.0-632.0) | 407.0 (300.0-606.0) | 409.0 (285.0-600.0) | <.001 |
| Urban, No. (%) | 107 962 (95.4) | 38.268 (96.6) | 28 095 (95.2) | 41 599 (94.3) | <.001 |
| Region, No. (%) | |||||
| Northeast | 28 394 (24.8) | 9969 (24.8) | 6406 (21.5) | 12 019 (27.1) | <.001 |
| Midwest | 23 146 (20.2) | 7074 (17.6) | 6961 (23.3) | 9111 (20.6) | |
| South | 39 420 (34.5) | 15 220 (37.9) | 10 522 (35.2) | 13 678 (30.9) | |
| West | 23 373 (20.4) | 7915 (19.7) | 5975 (20.0) | 9483 (21.4) | |
| Teaching, No. (%) | 93 123 (83.4) | 33 680 (85.2) | 24 282 (84.3) | 35 161 (81.1) | <.001 |
| Heart transplants, No. (%) | 11 971 (13.8) | 3139 (9.6) | 3187 (14.1) | 5645 (18.1) | <.001 |
Abbreviations: ARNI, Angiotensin Receptor Neprilysin Inhibitor; CHAMP, Civilian Health and Medical Program; NA, not available.
Continuous variables presented as median (IQR). Continuous and categorical variables compared using Wilcoxon rank sum test and χ2 tests, respectively.
Calculated as weight in kilograms divided by height in meters squared.
Other race includes patients who did not state their race or for whom a race was unable to be determined using existing documentation.
CardioMEMS Heart Failure System (Abbott Cardiovascular) is a device used to monitor pulmonary artery pressures.
Rates of ARNI prescribed at discharge increased steadily over the study period with 1.1% of patients (27 of 2451) discharged with an ARNI July 7, 2015, to September 30, 2015, compared with 55.4% of patients (1957 of 3536) discharged with an ARNI from October 1, 2022, to December 31, 2022. ACEI or ARB prescription at discharge fell from 88.3% (2612 of 2957) to 45.9% (2033 of 4434) over the same period, whereas rates of ARNI initiation at discharge in those not receiving therapy and rates of ACEI, ARN, or ARNI prescription at discharge also increased (from 1.1% [27 of 2450] to 44.8% [1245 of 2781] and from 71.1% [2639 of 3713] to 84.7% [3990 of 4711], respectively) over the study period (Figure 1 and eTables 2 and 3 in Supplement 1).
Figure 1. Trends in Angiotensin-Converting Enzyme Inhibitor (ACEI), Angiotensin II Receptor Blocker (ARB), and Angiotensin Receptor-Neprilysin Inhibitor (ARNI) Prescription Over Time.
A, Percentage ARNI prescribed at discharge. B, Percentage ARNI initiated at discharge. C, Percentage ACEI or ARB prescribed at discharge. D, Percentage ACEI, ARB, or ARNI prescribed at discharge. Dashed blue lines indicate date of ePublication of Comparison of Sacubitril-Valsartan vs Enalapril on Effect on N-Terminal Pro–Brain Natriuretic Peptide in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF; November 11, 2018) and date of ePublication of the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment (January 11, 2021).
In adjusted logistic regression analysis, patients discharged during period 2 and period 3 were found to have a 3.81-fold (95% CI, 3.65-3.98) and 9.15-fold (95% CI, 8.79-9.52) increased odds of ARNI prescription at discharge when compared with period 1, respectively. Patients discharged during periods 2 and 3 were further found to have an increased odds of ARNI initiation at discharge and a decreased odds of ACEI or ARB prescription at discharge (0.46; 95% CI, 0.45-0.48 and 0.25; 95% CI, 0.24-0.26, respectively) compared with period 1 (eTable 4 in Supplement 1).
Using adjusted piecewise logistic regression, patients discharged during periods 1, 2, and 3 were found to have a statistically significant increase in ARNI prescription at discharge (period 1: 27 of 2451 [1.1%] to 215 of 1273 [16.9%]; period 2: 294 of 1603 [18.3%] to 1392 of 3956 [35.2%]; period 3: 1564 of 4059 [38.5%] to 1957 of 3536 [55.4%]), ARNI initiation at discharge (period 1: 27 of 2450 [1.1%] to 114 of 1159 [9.8%]; period 2: 145 of 1444 [10.0%] to 633 of 2751 [23.0%]; period 3: 814 of 2893 [28.1%] to 1245 of 2781 [44.8%]), and ACEI, ARB, or ARNI prescription at discharge (period 1: 2639 of 3713 [71.1%] to 1471 of 1870 [78.7%]; period 2: 1825 of 2319 [78.8%] to 4323 of 5430 [79.6%]; period 3: 4579 of 5742 [79.8%] to 3990 of 4711 [84.7%]) in each time period (all P <.001) (Figure 2). When comparing rates of ARNI prescription between periods 1 and 2, patients discharged during period 2 were found to have a slightly lower rate of increase in ARNI prescription when compared with what would be expected if the rate of increase in prescription during period 1 had continued into period 2 (log odds slope period 1: 0.0017; period 2: 0.0012; P value for slope change <.001) (eTable 5 in Supplement 1). Predicted probabilities of ACEI or ARB prescription at discharge were found to significantly decrease over each time period (log odds slope period 1: −0.0007; period 2: −0.0009; period 3: −0.008; P <.001) (Figure 2; eTable 5 in Supplement 1). Hospital characteristics associated with ARNI prescription at discharge are shown in eTable 6 in Supplement 1.
Figure 2. Predicted Probabilities of Prescriptions at Discharge.
A, Angiotensin receptor-neprilysin inhibitor (ARNI) prescription at discharge. B, ARNI initiation at discharge among those not previously on ARNI at admission. C, Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) prescription at discharge. D, ACEI, ARB, or ARNI prescription at discharge. P values in each period evaluate for changes in prescription rate during that time period. P values at designated diamonds evaluate for change in slope between different time periods. Dashed blue lines indicate date of ePublication of Comparison of Sacubitril-Valsartan vs Enalapril on Effect on N-Terminal Pro–Brain Natriuretic Peptide in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF; November 11, 2018) and date of ePublication of the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment (January 11, 2021).
Discussion
In this cross-sectional analysis of 114 333 patients hospitalized with HFrEF from the GWTG-HF registry, the temporal trends in ARNI, ACEI or ARB, and ACEI or ARB or ARNI prescription patterns between July 7, 2015, and December 31, 2022, were analyzed. During this study period, ARNI and either ACEI or ARB or ARNI prescription at discharge increased whereas ACEI or ARB prescription at discharge decreased. When separating the time period studied into 3 segments based on major ARNI publications, we showed that patients discharged in the periods after the publication of the PIONEER-HF trial and after the publication of the 2021 Update to the 2017 Consensus for Optimization of Heart Failure Treatment had increased odds of ARNI prescription compared with the time period immediately after FDA approval of the drug. Although the rate of ARNI prescription increase slightly slowed after the publication of the PIONEER-HF trial and although the publication of the 2021 Update to the 2017 Consensus on Heart Failure treatment did not significantly impact the already increasing rate of ARNI prescription, ARNI prescription rates did continuously and significantly increase overall from 2015 to the end of 2022.
There often exists a substantial period between demonstration of medication efficacy and ultimate uptake by the medical community. In the seminal 2001 Institute of Medicine Report, an average delay of 17 years from trial publication to widespread uptake was reported.1 Although this delay has improved in the current day, there still exist a number of barriers to the uptake of new therapeutics including practitioner familiarity, initial drug cost, formulary availability, identification of appropriate eligible patients, comparative analyses to similar medications, comfort with adverse effect profiles, and overall cost-effectiveness.2,3 The accelerated uptake of sacubitril-valsartan compared with other guideline-directed medical therapies such as β-blockers and ACEI may be attributed to rapid publications targeted at these specific concerns.4,5 For example, in the PIONEER-HF trial, hospitalized patients with HFrEF who were randomized to ARNI use were found to have a significantly greater reduction in NT-proBNP level without a difference in rates of kidney dysfunction, hypotension, angioedema, or hyperkalemia.6 In an analysis of data from the original PARADIGM-HF trial, the 5-year number needed to treat (NNT) for all-cause mortality for ARNI compared with imputed placebo was 11, which was found to be similar to or better than that for β-blockers (NNT = 8), mineralocorticoid receptor antagonists (NNT = 15), implantable cardioverter defibrillator (NNT = 14), and cardiac resynchronization therapy (NNT = 14).7 In a cost-effectiveness analysis by Gaziano et al,8 inpatient initiation of sacubitril-valsartan was found to potentially save $92.3 million a year in health care costs with a concomitant gain of $170 to $300 million in increased societal productivity.
Limitations
This study has some limitations. Data collected are retrospective and observational, and therefore, causation cannot be implied. Although regression models were adjusted for possible confounders, the risk for residual confounding remains. Rates of ACEI, ARB, and ARNI prescription are slightly lower in our analysis compared with other analyses that used formal performance measure specifications, with expanded criteria for patient and system reason exclusions.9 Generalizability of our findings may be limited by the voluntary nature of GWTG-HF registry participation and the focus of the registry on quality improvement.
Conclusions
Results of this cross-sectional study reveal that rates of ARNI prescription at discharge and initiation at discharge have steadily increased since FDA approval of sacubitril-valsartan in 2015 with a concomitant decrease in rates of ACEI or ARB use over the same time period. Although ARNI prescription rates at discharge have substantially increased, overall prescription of ARNI at discharge was 55.4% among eligible hospitalized patients with HFrEF at the end of 2022, suggesting significant remaining opportunities for risk and mortality reduction with improved implementation of ARNI among hospitalized patients with HFrEF.
eMethods.
eTable 1. Missingness of the Cohort
eTable 2. ACEI/ARB/ARNI Prescription Rates Over Time
eTable 3. ACEI/ARB/ARNI Prescription Rates Over 3 Study Time Periods
eTable 4. Association of Time Period With RAASi Prescription at Discharge
eTable 5. Slope (Log-Odds) Estimates During the 3 Time Periods and Changes in Slopes Between Periods
eTable 6. Association of Hospital Characteristics With ARNI Prescription at Discharge Within Each Time Period
Data Sharing Statement.
References
- 1.Institute of Medicine Committee on Quality of Health Care in America . Crossing the Quality Chasm: A New Health System for the 21st Century. National Academies Press; 2001. [PubMed] [Google Scholar]
- 2.Luo N, Fonarow GC, Lippmann SJ, et al. Early adoption of sacubitril/valsartan for patients with heart failure with reduced ejection fraction: insights from Get With the Guidelines-Heart Failure (GWTG-HF). JACC Heart Fail. 2017;5(4):305-309. doi: 10.1016/j.jchf.2016.12.018 [DOI] [PubMed] [Google Scholar]
- 3.Medlinskiene K, Tomlinson J, Marques I, Richardson S, Stirling K, Petty D. Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review. BMC Health Serv Res. 2021;21(1):1198. doi: 10.1186/s12913-021-07196-4 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lee DS, Tu JV, Juurlink DN, et al. Risk-treatment mismatch in the pharmacotherapy of heart failure. JAMA. 2005;294(10):1240-1247. doi: 10.1001/jama.294.10.1240 [DOI] [PubMed] [Google Scholar]
- 5.Parameswaran AC, Tang WH, Francis GS, Gupta R, Young JB. Why do patients fail to receive beta-blockers for chronic heart failure over time? a “real-world” single-center, 2-year follow-up experience of β-blocker therapy in patients with chronic heart failure. Am Heart J. 2005;149(5):921-926. doi: 10.1016/j.ahj.2004.07.026 [DOI] [PubMed] [Google Scholar]
- 6.Angiotensin-neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2019;380(11):1090. doi: 10.1056/NEJMoa1812851 [DOI] [PubMed] [Google Scholar]
- 7.Srivastava PK, Claggett BL, Solomon SD, et al. Estimated 5-year number needed to treat to prevent cardiovascular death or heart failure hospitalization with angiotensin receptor-neprilysin inhibition vs standard therapy for patients with heart failure with reduced ejection fraction: an analysis of data from the PARADIGM-HF Trial. JAMA Cardiol. 2018;3(12):1226-1231. doi: 10.1001/jamacardio.2018.3957 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD. Cost-effectiveness of sacubitril-valsartan in hospitalized patients who have heart failure with reduced ejection fraction. JAMA Cardiol. 2020;5(11):1236-1244. doi: 10.1001/jamacardio.2020.2822 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Keshvani N, Mehta A, Alger HM, et al. Heart failure quality of care and in-hospital outcomes during the COVID-19 pandemic: findings from the Get With The Guidelines-Heart Failure registry. Eur J Heart Fail. 2022;24(6):1117-1128. doi: 10.1002/ejhf.2484 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eMethods.
eTable 1. Missingness of the Cohort
eTable 2. ACEI/ARB/ARNI Prescription Rates Over Time
eTable 3. ACEI/ARB/ARNI Prescription Rates Over 3 Study Time Periods
eTable 4. Association of Time Period With RAASi Prescription at Discharge
eTable 5. Slope (Log-Odds) Estimates During the 3 Time Periods and Changes in Slopes Between Periods
eTable 6. Association of Hospital Characteristics With ARNI Prescription at Discharge Within Each Time Period
Data Sharing Statement.