Table 1 Summary of major randomized controlled trials on angiotensin receptor neprilysin inhibitor
Trial | Intervention | Comparator | Inclusion criteria | Primary endpoints | Outcomes |
|---|---|---|---|---|---|
PARADIFM-HF (2014) (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 CVD 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) |
TITRATION (2016) (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 |
PIONEER-HF (2019) (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 |
PARAMOUNT (2012) (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) |
PARAGON-HF (2019) (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) |
EVALUATE-HF (2019) (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% NYHA II–IV | 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 |