Is Sacubitril/Valsartan a Superior Agent in Heart Failure With Reduced Ejection Fraction? A Review of Randomized...

Area of Science:

• Cardiology
• Pharmacology
• Clinical Trials

Background:

• The PARADIGM HF trial established sacubitril/valsartan (SV) superiority over enalapril in heart failure with reduced ejection fraction (HFrEF).
• Conflicting results have emerged from subsequent trials comparing SV to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in HFrEF.

Purpose of the Study:

• To systematically review randomized comparative trials of SV against ACEIs or ARBs in HFrEF patients.
• To evaluate the consistency of SV's benefits across different study populations and endpoints.

Main Methods:

• Searched PubMed and Embase databases for randomized comparative trials using terms like sacubitril, angiotensin neprilysin, and LCZ696.
• Excluded meta-analyses, retrospective, ad hoc, and cohort studies, focusing solely on randomized comparative trials.
• Analyzed 11 selected randomized comparative trials comparing SV to ACEI or ARB in HFrEF.

Main Results:

• The mortality and quality-of-life benefits of SV over enalapril, as reported in PARADIGM HF, were not replicated in subsequent trials.
• The impact of SV on heart failure hospitalizations was inconsistent across the reviewed studies.
• No significant improvement in exercise tolerance was observed with SV compared to enalapril in these trials.

Conclusions:

• The findings from the landmark PARADIGM HF trial regarding SV's benefits in HFrEF have not been consistently confirmed in subsequent randomized comparative trials.
• Further research may be needed to clarify the role of SV in HFrEF management and identify patient subgroups that benefit most.