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Table 1 Summary of major randomized controlled trials on angiotensin receptor neprilysin inhibitor

From: Will introduction of ARNI reduce the need of device therapy in heart failure with reduced ejection fraction?

Trial Intervention Comparator Inclusion criteria Primary endpoints Outcomes
(n = 8399)
F/up 27 months
Sacubitril/vvalsartan Enalapril -LVRF ≤ 35
-NYHA classes II–IV
-Elevated NP
Composite of CVD or HF hospitalization Primary endpoint
HR = 0.80 (0.73–0.87)
P = 0.0000002
HR = 0.80 (0.71–0.89)
P = 0.00004
All-cause mortality
HR = 0.84 (0.76–0.93)
P < 0.0001
Symptomatic hypotension (14% vs 9.2%; P < 0.001)
(n = 498)
F/up 12 weeks
Condensed regimen (full dose of ARNI by 3 weeks) Comparator regimen (full dose of ARNI by 6 weeks) LVEF ≤ 35%
NYHA classes II–IV
Adverse events (hypotension, renal dysfunction, hyperkalemia, angioedema) No significant difference
(n = 881)
F/up 8 weeks
Sacubitril/valsartan Enalapril LVEF ≤ 40%
Elevated NP
Hospitalized for ADHF
Time-averaged change of NT-proBNP Primary endpoint
HR 0.71 (0.63–0.81), P < 0.05
HF rehospitalization 8.0 % vs. 13.8%, P < 0.05
(n = 301)
F/up 12 weeks
Sacubitril/valsartan Valsartan LVEF ≥45%
NYHA classes II–III
Elevated NP
Change in NT-pro BNP from baseline Significant change in favor of ARNI:
Ratio 0.77 (0.64–0.92)
(n = 4822)
F/up 35 months
Sacubitril/valsartan Valsartan LVEF ≥ 45%
NYHA classes II–III
Elevated NP
Composite of HF hospitalizations and CVDs Non-significant
Relative risk 0.87 (0.75–1.01)
(n = 464)
F/up 12 weeks
Sacubitril/valsartan Enalapril LVEF ≤40%
NYHA classes I–III
History of hypertension
Aortic characteristic impedance (Zc) Non-significant difference in two groups
PRIME (2019)
(n = 118)
F/up 12 months
Sacubitril/valsartan Valsartan LVEF 25–50%
NYHA classes I–III
Chronic functional MR (EROA >  0.1 cm2 despite optimal medical therapy)
Change in EROA Significant decrease in EROA ( 0.04cm2), regurgitant volume ( 7.3 ml), LVEDVI ( 7.01 ml)
PROVE-HF (2019)
(n = 794)
F/up 12 months
Sacubitril/valsartan ACEi/ARB LVEF ≤ 40%
Correlation between change in NT-pro BNP and remodeling (LVEF, LVEDVi, LVESVi, LAVi, E/E/e' at 12 months Significant correlations observed between the change in NT-proBNP concentration and all cardiac remodeling parameters
  1. ACEi Angiotensin-converting enzyme inhibitor, ADHF Acute decompensated heart failure, ARB Angiotensin receptor blocker, ARNI Angiotensin receptor neprolysin inhibitor, CV Cardiovascular, CVD Cardiovascular death, E/e' Ratio of early mitral diastolic filling velocity/early diastolic mitral annular velocity, EROA Effective regurgitant orifice area, EVALUATE-HF Effect of Sacubitril-Valsartan Versus Enalapril on Aortic Stiffness in Patients with Heart Failure and Reduced Ejection Fraction, F/up Follow-up, HF Heart failure, HR Hazard ratio, LAVi Left atrial volume index, LVEDVi LV end-diastolic volume index, LVEF Left ventricular ejection fraction, LVESVi LV end-systolic volume index, MR Mitral regurgitation, NP Natriuretic peptide, NT-proBNP N-terminal-pro B-type NP, NYHA New York Heart Association, PARADIGM-HF Prospective comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure, PARAGON-HF Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction, PARAMOUNT Prospective comparison of ARNI with ARB on Management Of heart failure with preserved ejection fraction, PIONEER-HF Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode, PRIME Pharmacological Reduction of Functional, Ischemic Mitral Regurgitation, PROVE-HF Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure, RFT Renal function test, Change