A systematic review of 17,327 patients found sacubitril/valsartan (which works by boosting natriuretic peptide levels) reduced heart failure hospitalizations, lowered NT-proBNP, and protected kidney function better than ACE inhibitors and ARBs.
17,327 patients analyzedSacubitril/valsartan reduced HF hospitalizations, lowered NT-proBNP, and preserved kidney function compared to ACEi/ARBs with no excess cardiovascular death risk
What the researchers found
Across large-scale RCTs involving 17,327 participants with an average follow-up of ~2.9 years, sacubitril/valsartan compared to ACE inhibitors and ARBs showed:
- Notable reduction in NT-proBNP levels (a peptide biomarker of heart failure severity)
- Prevention of further deterioration in renal function
- Decreased hospitalizations for heart failure
- No increased risk of cardiovascular mortality
- Benefits observed across different types of heart failure and regardless of renal status
Why it matters
Heart failure is a leading cause of hospitalization and death worldwide. Sacubitril/valsartan works through a unique mechanism — by boosting natriuretic peptide levels through neprilysin inhibition — representing a fundamentally new approach to heart failure treatment. The additional kidney protection is particularly important since many heart failure patients also have kidney disease.
How the study worked
Systematic review of randomized controlled trials identified through PubMed, PMC, and Google Scholar. Large-scale RCTs comparing sacubitril/valsartan to ACE inhibitors or ARBs in heart failure patients were analyzed. Efficacy outcomes included cardiovascular death, heart failure hospitalization rates, and NT-proBNP changes. Renal outcome was assessed as impairment of renal function.
What this study cannot tell us
The systematic review did not include a formal meta-analysis with pooled statistics. The search was limited to three databases. Individual trial populations varied in heart failure type, severity, and comorbidities, which may affect comparability. Long-term data beyond the average 2.9-year follow-up is limited. The review focused on comparison with ACEi/ARB but didn't compare to newer agents like SGLT2 inhibitors.
How to read the evidence
This is a systematic review of randomized controlled trials — a high level of evidence. However, the lack of a formal meta-analysis and limited database search somewhat reduce the certainty of the conclusions compared to a Cochrane-style systematic review.
When this study was published
Published in 2024, this review captures the latest RCT evidence supporting sacubitril/valsartan as a cornerstone heart failure therapy.
The bigger picture
Sacubitril/valsartan represents a paradigm shift in heart failure treatment by harnessing the body's own natriuretic peptide system. By blocking neprilysin (the enzyme that breaks down beneficial peptides like BNP and ANP), the drug amplifies their protective effects on the heart and kidneys. This approach has transformed heart failure guidelines and opened research into neprilysin inhibition for other cardiovascular conditions.
Questions still open
- Does sacubitril/valsartan provide additive benefit when combined with SGLT2 inhibitors in heart failure?
- Could neprilysin inhibition benefit patients with chronic kidney disease who don't have heart failure?
- Are there specific natriuretic peptide levels that predict which patients will respond best to sacubitril/valsartan?
Common questions
How does sacubitril/valsartan relate to peptides?
Is sacubitril/valsartan better than standard heart failure drugs?
Read the original research
Efficacy of Angiotensin Receptor-Neprilysin Inhibitor and Its Renal Outcome in Heart Failure Patients: A Systematic Review of Randomized Clinical Trials.
Cureus, 16(2), e54501
Citation
Almansouri, Naiela E; Bakkannavar, Saloni; Faheem, Youmna; Jaiswal, Amisha; Shergill, Kainaat; Boppana, Kusalik; Nath, Tuheen Sankar. (2024). Efficacy of Angiotensin Receptor-Neprilysin Inhibitor and Its Renal Outcome in Heart Failure Patients: A Systematic Review of Randomized Clinical Trials.. Cureus, 16(2), e54501. https://doi.org/10.7759/cureus.54501