Association of Change in N-Terminal Pro–B-Type Natriuretic Peptide Following Initiation of Sacubitril-Valsartan Treatment With Cardiac Structure and Function in Patients With Heart Failure With Reduced Ejection Fraction

Abstract

IMPORTANCE In patients with heart failure and reduced ejection fraction (HFrEF), treatment with sacubitril-valsartan reduces N-terminal pro-b-type natriuretic peptide (NT-proBNP) concentrations. The effect of sacubitril-valsartan on cardiac remodeling is uncertain. OBJECTIVE To determine whether NT-proBNP changes in patients with HFrEF treated with sacubitril-valsartan correlate with changes in measures of cardiac volume and function. DESIGN, SETTING, AND PARTICIPANTS Prospective, 12-month, single-group, open-label study of patients with HFrEF enrolled in 78 outpatient sites in the United States. Sacubitril-valsartan was initiated and the dose adjusted. Enrollment commenced on October 25, 2016, and follow-up was completed on October 22, 2018. EXPOSURES NT-proBNP concentrations among patients treated with sacubitril-valsartan. MAIN OUTCOMES AND MEASURES The primary outcome was the correlation between changes in log 2-NT-proBNP concentrations and left ventricular (LV) EF, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), left atrial volume index (LAVI), and ratio of early transmitral Doppler velocity/early diastolic annular velocity (E/e′) at 12 months. RESULTS Among 794 patients (mean age, 65.1 years; 226 women [28.5%]; mean LVEF = 28.2%), 654 (82.4%) completed the study. The median NT-proBNP concentration at baseline was 816 pg/mL (interquartile range [IQR], 332-1822) and 455 pg/mL (IQR, 153-1090) at 12 months (difference, P < .001). At 12 months, the change in log 2-NT-proBNP concentration was correlated with changes in LVEF

Reappraisal on pharmacological and mechanical treatments of heart failure

“…These findings of sacubitril/valsartan with stunning interest laid the foundation forrecommendations in guidelines [2,7,16]. PIONEER-HF further confirmed the necessity of early use of sacubitril/valsartan in HFrEF [24], and the reduction in N-terminal pro-B-type natriuretic peptide (NT-pro BNP) concentration was weakly yet significantly correlated with reverse cardiac remodelling at 12 months [25]; however, sacubitril/valsartan showed no better reduction in central aortic stiffness than enalapril in HFrEF [26]. An analysis of the TRANSITION study indicated that sacubitril/valsartan has promising results in patients who are naïve to angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) treatment [27] as well as in patients with de novo HFrEF [28].…”

“…Pharmacotherapy Tolvaptan TACTICS-HF [8], AQUAMARINE [9,10], Shirakabe et al [11], EVEREST [12], SECRET, QUEST, METEOR [13] Ivabradine SHIFT [14,15], INTENSIFY, ETHIC-AHF, Bagriy et al [17], CARVIVA HF [18] Sacubitril/valsartan PARADIGM-HF [19][20][21][22][23], PIONEER-HF [24,25], EVALUATE-HF [26], TRANSITION [27,28], PARAMOUNT [29,30], PARAGON-HF [31] Nebivolol SENIORS [33][34][35][36][37], Sessa et al [38], Brehm et al [39], ELANDD [40], CARNEBI [41] Levosimendan LIDO [42], SURVIVE [43], REVIVE [44], LevoRep [45], Zhang et al [46], LION-HEART [47], LEAF [48], Jia et al [49], LAICA [50], Leo-DOR [51] MRA Eplerenone: EPHESUS [75], EMPHASIS-HF [52][53][54][55]…”

Sacubitril-Valsartan, a New Opportunity for Heart Failure with Recovered Ejection Fraction?

“…Compared with baseline, the 6-and 12-month least-square mean improvements in LVEF were 5.2% (95% CI 4.8-5.6) and 9.4% (95% CI 8.8-9.9), respectively (p < 0.001 for both); 75% of the study participants had an LVEF increase of 4.9% or greater and 25% experienced an LVEF increase of 13.4% or greater at 12 months. The greater benefits were observed in those patients with newonset HF or those not taking an ACEI or ARB at baseline [3].…”

“…In the PROVE trial analyses of changes in cardiac remodeling indices demonstrated a significant increase in LVEF and corresponding reduction in LV volumes as early as 6 months; and such changes continued at 12 months [3]. Compared with baseline, the 6-and 12-month least-square mean improvements in LVEF were 5.2% (95% CI 4.8-5.6) and 9.4% (95% CI 8.8-9.9), respectively (p < 0.001 for both); 75% of the study participants had an LVEF increase of 4.9% or greater and 25% experienced an LVEF increase of 13.4% or greater at 12 months.…”

Angiotensin–neprilysin inhibition in de novo heart failure – starting off strong

“…As such, a proposed implementation strategy is to consider initiation early in the course of HFrEF, including at the time of index diagnosis, and even prior to exposure to RAAS inhibitors. This up‐front strategy has potential advantages including the ability to influence congestion, ventricular remodelling, lower readmissions and mortality, and improve health status including quality of life earlier in the disease course, but the safety and tolerability of such an approach, particularly in patients who have not previously shown tolerance to ACEI/ARB, has been previously not well characterized.…”