Sodium-Glucose Cotransporter 2 Inhibitors First Strategy Improve Decongestion in Patients with Symptomatic Heart Failure and Reduced Ejection Fraction When Compared to Angiotensin Receptor Neprilysin Inhibitor First Strategy

Wei-Chieh Lee^1,2,3,*, Wei-Ting Chang^1,2, Chon-Seng Hong², Chia-Te Liao², Po-Sen Huang², Shen-Chung Huang², Chih-Hsien Lin², Chun-Yen Chiang², Zhih-Cherng Chen^2,3, Jhih-Yuan Shih^2,3,*

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¹ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 70101 Tainan, Taiwan

² Division of Cardiology, Department of Internal Medicine, Chi Mei Medical Center, 71004 Tainan, Taiwan

³ School of Medicine, College of Medicine, National Sun Yat-sen University, 80424 Kaohsiung, Taiwan

^*Correspondence: leeweichieh@yahoo.com.tw (Wei-Chieh Lee); s841027@gmail.com (Jhih-Yuan Shih)

Front. Biosci. (Landmark Ed) 2023, 28(4), 81; https://doi.org/10.31083/j.fbl2804081

Submitted: 14 February 2023 | Revised: 14 April 2023 | Accepted: 19 April 2023 | Published: 27 April 2023

(This article belongs to the Special Issue An Update on Sodium Glucose Co-Transporters)

This is an open access article under the CC BY 4.0 license.

Abstract

Background: Angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) are emerging medical treatments for decompensated heart failure (HF) with reduced ejection fraction. In clinical practice, the combination of ARNI and SGLT2i cannot be administered owing to the poor hemodynamic status in patients with HF with reduced ejection fraction (HFrEF). This study aimed to compare different strategies of HF management for ARNI first or SGLT2i first in such a population. Methods: From January 2016 to December 2021, 165 patients were diagnosed with HFrEF and New York Heart Association functional class $\geq$ II and already received optimal medical treatment. Ninety-five patients received the ARNI-first strategy, and 70 patients received the SGLT2i-first strategy according to the physician’s choice. Age, sex, hemodynamic condition, etiologies of HF, comorbidities, serum creatinine, N-terminal pro-B-type natriuretic peptide (NT-ProBNP), echocardiographic parameters, and clinical outcomes were compared between the ARNI and SGLT2i-first strategy groups. Results: In the SGLT2i-first group, the median interval between the addition of the second medication was longer (ARNI-first vs. SGLT2i-first; 74 [49–100] days vs. 112 [86–138] days; p = 0.044). Improvement in left ventricular ejection fraction (LVEF), change in left atrial dimension, and change in left ventricular end-diastolic and end-systolic volume (LVESV) did not differ between the two groups. The incidence of HF hospitalization, cardiovascular mortality, and all-cause mortality did not differ between the two groups. A non-significant trend of lower NT-proBNP levels (ARNI-first vs. SGLT2i-first; 1383 [319–2507] pg/mL vs. 570 [206–1314] pg/mL; p = 0.055) and significantly higher discontinuation rate of diuretic agents (ARNI-first vs. SGLT2i- first; 6.8% vs. 17.5%; p = 0.039) were noted in the SGLT2i-first group. When early combination ( $\leq$ 14D) compared to late combination ( $>$ 14D), better positive remodeling of LVESV presented significantly in early combination subgroups. Conclusions: In patients with symptomatic HFrEF, SGLT2i-first strategy may provide a higher possibility of discontinuing diuretic agents than the ARNI-first strategy. Changes in LV performance, progression of renal function, and clinical outcomes did not differ between the two groups. Early combination ( $\leq$ 14D) provided better LV remodeling.

Keywords

heart failure with reduced ejection fraction

angiotensin receptor neprilysin inhibitor

sacubitril/valsartan

sodium-glucose cotransporter 2 inhibitors

decongestion

early combination

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Fig. 1.

The improving ejection fraction, decreasing left ventricular end-diastolic volume, and decreasing left ventricular end-systolic volume when early combination ( $\leq$ 14D) compared to late combination ( $>$ 14D). (A) A non-significant trend of improving ejection fraction $>$ 5% presented when early combination ( $\leq$ 14D) compared to late combination ( $>$ 14D) ( $\leq$ 14D vs. $>$ 14D; 80.0% vs. 64.8%; p = 0.060). (B) The decreasing left ventricular end-diastolic volume $>$ 10% did not differ between early combination ( $\leq$ 14D) and late combination ( $>$ 14D) groups ( $\leq$ 14D vs. $>$ 14D; 52.0% vs. 41.1%; p = 0.221). (C) The decreasing left ventricular end-systolic volume $>$ 10% showed significant higher when early combination ( $\leq$ 14D) compared to late combination ( $>$ 14D) group ( $\leq$ 14D vs. $>$ 14D; 72.0% vs. 54.4%; p = 0.042). Abbreviation: EF, ejection fraction; LVEDV, left ventricular end-systolic volume; LVESV, left ventricular end-systolic volume; ARNI, angiotensin receptor neprilysin inhibitor; SGLT2i, sodium-glucose cotransporter 2 inhibitors; D, day.

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Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698