Posters Highlight Clinical Impact of, Prescription Barriers to Sacubitril/Valsartan

Two posters released as part of the Heart Failure Society of America (HFSA) Annual Scientific Meeting highlighted the effects of sacubitril/valsartan (Entresto; Novartis) on key biomarkers and cardiac function in patients with heart failure with reduced ejection fraction (HFrEF), while also addressing prescription barriers for providers; the meeting was set to be conducted in Atlanta, Georgia, last month but was canceled due to Hurricane Helene.

Two posters highlighted the effects of sacubitril/valsartan (Entresto; Novartis) on key biomarkers and cardiac function in patients with heart failure with reduced ejection fraction (HFrEF), while also addressing prescription barriers for providers. | Image Credit: New Africa - stock.adobe.com

Sacubitril/Valsartan's Effect on Biomarkers and Cardiac Function

Sacubitril/valsartan represents a new medication class for patients with HFrEF. Therefore, the first poster analyzed the impact of sacubitril/valsartan on biomarkers galectin-3, soluble suppression of tumorigenesis-2 (sST2), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association with echocardiographic data to better understand their clinical utility in HF prognosis and treatment.¹

The researchers conducted a retrospective chart review of 81 patients with HFrEF treated with sacubitril/valsartan, recording cardiac function parameters and biomarker levels at baseline and about 3 months, 6 months, 1 year, 2 years, and 3 years post-treatment initiation.

Due to the nature of the review, they explained that obtaining data at these exact time points for each variable was challenging, leading to the inclusion of values within a set interval range. Also, patients without known treatment start dates or minimal data points were excluded, resulting in a final study population of 61 patients

Over the 3-year treatment period, the researchers observed significant reductions in NT-proBNP levels (2669.87 vs 887.62; P = .0066), while no significant changes were noted in sST2 (33.78 vs 30.76; P = .5462) or galectin-3 (18.1 vs 24.44; P = .2509).

However, significant differences in galectin-3 (P = .0096) and sST2 (P = .0326) levels were observed between the ischemic and nonischemic cardiomyopathy cohorts; NT-proBNP levels (P = .5651) showed no significant difference. This suggested that different underlying HF causes may affect biomarker levels differently.

Lastly, echocardiographic data revealed that, after 3 years, there was no significant difference in patients’ left ventricular internal dimension at end-diastole (5.8 cm vs 5.6 cm; P = .5375), but their left ventricular ejection fraction did differ significantly (28.25% vs 41.41%; P < .0001). Notably, both echocardiographic measures were strongly correlated with changes in all 3 biomarkers, suggesting a potential association between cardiac remodeling and biomarker dynamics.

“Despite no significant change in sST2 and galectin-3 over the 3-year time period, these biomarkers may serve as valuable additions in determining response to treatment as levels correlated well between ischemic and [nonischemic cardiomyopathy] groups and with echocardiographic parameters [left ventricular ejection fraction] and [left ventricular internal dimension at end-diastole] across the time points,” the authors concluded.

Barriers to Sacubitril/Valsartan Prescripton

Building on the previous poster, previous research has shown that sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), reduces hospitalization and mortality more effectively than angiotensin-converting enzyme (ACE) inhibitors in patients with HFrEF.² However, the high cost of ARNIs compared to ACE inhibitors and angiotensin receptor blockers (ARBs) poses a prescription barrier. The second poster compared the prescription rates of ARB, ACE, and ARNI at the Atlanta VA (AVAMC) and summarized providers’ attitudes toward prescribing ARNIs.³

The researchers used the VA Heart Failure Dashboard to compare demographics, baseline blood pressure, ejection fraction, and glomerular filtration rate for patients on ARB and ACE compared to no ACE or ARB. Also, they surveyed 59 providers on their perception of ACE, ARB, and ARNI prescriptions at the AVAMC.

From the dashboard, the researchers determined that 324 patients were on an ACE or ARB, while 186 remained untreated. Among the 2 groups, they found no statistical difference between systolic blood pressure (125.6 vs 122.7; P = .06), glomerular filtration rate (66.0 vs 63.8; P = .65), or ejection fraction (29.8 vs 28.7l; P = .14). Additionally, at AVAMC, there was a similar prescription rate of ARNI compared to other VA hospitals (38.8% vs 42.3%) but a higher percentage than non-VA hospitals, which prescribed them to between 6% and 22% of patients.

Of the 59 providers surveyed, most said they were very comfortable with prescribing ARNI. However, they listed 3 common limitations for prescribing ARNI: cost/prior authorization (n = 40), side effects (hypotension/hyperkalemia; n = 21), and the patients already initiated an ACE/ARB (n = 18).

“Further steps are underway to distribute survey results on a national scale as well as implement strategies to increase ARNI prescription rates and increase cost awareness to both providers and patients,” the authors concluded.

References

1. Gillet SA, Kohli P. Characteristics of patients eligible for sacubitril valsartan optimization and provider’s attitudes towards renin-angiotensin system blockers. Prepared for: HFSA 2024; September 27-30, 2024 (canceled); Atlanta, Georgia. Poster.
2. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371(11):993-1004. doi:10.1056/NEJMoa1409077
3. Agusala V, Chuckaree I, Gogineni N, Nair N. Sacubitril-valsartan effects on heart failure biomarkers: clinical implications. Prepared for: HFSA 2024; September 27-30, 2024 (canceled); Atlanta, Georgia. Poster.