Table 1.
Summary of the results of major randomized controlled trials of sacubitril/valsartan therapy according to disease entity
| Topic | Study | Year | Author | Patients | Number | Intervention | Comparator | Primary endpoint | F/U duration |
|---|---|---|---|---|---|---|---|---|---|
| HFrEF | PARADIGM-HF [4] | 2014 | McMurray et al. | LVEF ≤ 40% | 8,399 | Sacubitril/valsartan | Enalapril | CV death or first hospitalization for worsening HF | 27 mon (median) |
| NYHA class II–IV | |||||||||
| Elevated NP | |||||||||
| TITRATION [27] | 2016 | Senni et al. | LVEF ≤ 35% | 498 | Condensed regimen | Conservative regimen | Pre-specified adeverse events (hypotension, renal dysfunction, hyperkalemia, angioedema) | 12 wk | |
| NYHA class II–IV | |||||||||
| EVALUATE-HF [51] | 2019 | Desai et al. | LVEF ≤ 40% | 464 | Sacubitril/valsartan | Enalapril | Aortic characteristic impedance (Zc) | 12 wk | |
| NYHA class I–III | |||||||||
| History of hypertension | |||||||||
| HFrEF with functional MR | PRIME [49] | 2019 | Kang et al. | LVEF 25%–50% | 118 | Sacubitril/valsartan | Valsartan | Changes in EROA | 12 mon |
| NYHA class I–III | |||||||||
| Chronic functional MR (EROA > 0.1 cm2 despite 6 mon of RAS blocker and BB) | |||||||||
| Acute HF | PIONEER-HF [29] | 2019 | Velazquez et al. | LVEF ≤ 40% | 881 | Sacubitril/valsartan | Enalapril | Time-averaged change of NT-proBNP | 8 wk |
| Elevated NP | |||||||||
| Hospitalized for ADHF | |||||||||
| TRANSITION [34] | 2019 | Wachter et al. | LVEF ≤ 40% | 1,002 | Pre-discharge | Post-discharge | Target sacubitril/valsartan dose of 97/103 mg bid at the end of week 10 | 10 wk | |
| NYHA class II–IV | |||||||||
| Hospitalized for ADHF | |||||||||
| HFpEF | PARAMOUNT [36] | 2012 | Solomon et al. | LVEF ≥ 45% | 301 | Sacubitril/valsartan | Valsartan | Change in NT-proBNP from baseline to 12 wk | 12 wk |
| NYHA class II–III | |||||||||
| Elevated NP | |||||||||
| History of HF | |||||||||
| On diuretic therapy | |||||||||
| PARAGON-HF [38] | 2019 | Solomon et al. | LVEF ≥ 45% | 4,822 | Sacubitril/valsartan | Valsartan | Total hospitalizations for HF and CV death | 35 mon (median) | |
| NYHA class II–III | |||||||||
| Elevated NP | |||||||||
| Signs and symptoms of HF | |||||||||
| Structural heart disease | |||||||||
| On diuretic therapy |
FU, follow-up; HFrEF, heart failure with reduced ejection fraction; PARADIGM-HF, Prospective comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; NP, natriuretic peptide; CV, cardiovascular; HF, heart failure; PRIME, Pharmacological Reduction of Functional, Ischemic Mitral REgurgitation; MR, mitral regurgitation; EROA, effective regurgitant orifice area; RAS, renin-angiotensin system; BB, beta-blocker; PIONEER-HF, Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilized from an Acute Heart Failure Episode; ADHF, acute decompensated heart failure; NT-proBNP, N-terminal-pro B-type NP; HFpEF, heart failure with preserved ejection fraction; PARAMOUNT, Prospective comparison of ARNI with ARB on Management Of heart failUre with preserved ejectioN fracTion; PARAGON-HF, Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction.