Effects of Angiotensin Receptor/Neprilysin Inhibitor Therapy on Amino-terminal Pro-B-Type Natriuretic Peptide and Cardiac Remodeling in Heart Failure with Reduced Ejection Fraction: The PROVE-HF Study

Heart failure with reduced ejection fraction remains a prevalent clinical syndrome associated with significant morbidity and mortality. Despite significant advances in heart failure with reduced ejection fraction pharmacotherapy, 5-year mortality remains 50%. Sacubitril/valsartan is a first-in-class angiotensin-receptor-neprilysin inhibitor, Food and Drug Administration–approved to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure with reduced ejection fraction. Sacubitril/valsartan is recognized as a significant therapeutic advancement and endorsed by national guidelines, yet adoption into clinical practice has lagged across the United States. Recommendations for use differ greatly between the Prospective Comparison of Angiotensin-Receptor-Neprilysin Inhibitor with Angiotensin-Converting-Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure clinical trial, international guidelines, and the Food and Drug Administration-approved labeling, which can lead to uncertainty with prescribing. It is essential to establish an evidence-based, pragmatic approach to patient selection and management of sacubitril-valsartan facilitate integration into clinical practice. This review summarizes the pharmacology of sacubitril/valsartan, its known benefits and risks, and important considerations for incorporating sacubitril/valsartan into chronic heart failure management.

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Effect of Angiotensin Receptor-Neprilysin Inhibitor and Sodium-Glucose Co-transporter-2 Inhibitor Combination Therapy in Diabetic Patients with Heart Failure with Reduced Ejection Fraction: A Retrospective Study

10.21203/rs.3.rs-449007/v1 ◽

2021 ◽

Author(s):

Hyue Mee Kim ◽

In-Chang Hwang ◽

Wonsuk Choi ◽

Yeonyee E. Yoon ◽

Goo-Yeong Cho

Keyword(s):

Heart Failure ◽

Combination Therapy ◽

Ejection Fraction ◽

Diabetic Patients ◽

Angiotensin Receptor ◽

Reduced Ejection Fraction ◽

Neprilysin Inhibitor ◽

Patients With Heart Failure ◽

Angiotensin Receptor Neprilysin Inhibitor ◽

Group 1

Abstract Background Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose co-transporter-2 inhibitor (SGLT2i) have shown robust benefits in improving cardiac function and disease prognosis in diabetic patients with heart failure with reduced ejection fraction (HFrEF). However, their combined effect has not been revealed. Methods We retrospectively identified diabetic patients with HFrEF who were prescribed an ARNI and/or SGLT2i. Diabetic patients with HFrEF treated with standard HF therapy but not ARNI or SGLT2i were included as controls. The patients were divided into groups treated with both ARNI and SGLT2i (group 1), ARNI but not SGLT2i (group 2), SGLT2i but not ARNI (group 3), and neither ARNI nor SGLT2i (group 4). After propensity score-matching, the occurrence of hospitalization for heart failure (HHF), cardiovascular mortality, and changes in echocardiographic parameters were analyzed. Results Of the 206 matched patients included in the study, 90 (43.7%) had to undergo HHF and 43 (20.9%) died of cardiovascular causes during a median 25 months of follow-up. Patients in group 1 exhibited a lower risk of HHF and cardiovascular mortality compared to those in the other groups. Improvements in the left ventricular ejection fraction and mitral E/e’ were more pronounced in group 1 than in groups 2, 3 and 4. These echocardiographic improvements were more prominent after the initiation of ARNI, compare to the initiation of SGLT2i. Conclusion In diabetic patients with HFrEF, combination of ARNI and SGT2i showed significant improvement in cardiac function and prognosis. ARNI-SGLT2i combination therapy may improve the clinical course of HFrEF in diabetic patients.

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