Key result
Sacubitril/valsartan shows no mortality or quality of life benefit over enalapril across 11 subsequent trials.
Why the study?
Randomized trials comparing sacubitril/valsartan to an ACEI or ARB in HFrEF following PARADIGM HF showed conflicting results regarding mortality, hospitalizations, and quality of life.
Does sacubitril/valsartan improve mortality, hospitalizations, and quality of life compared to ACEI or ARB in patients with HFrEF?
Does sacubitril/valsartan improve mortality, hospitalizations, and quality of life compared to ACEI or ARB in patients with HFrEF?
Answers are grounded in this paper and cite their sources.
This systematic review suggests that the mortality and quality of life benefits of sacubitril/valsartan observed in the PARADIGM HF trial have not been consistently replicated in subsequent randomized trials.
Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials.
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Rindone et al. (2023) conducted a review in Heart Failure With Reduced Ejection Fraction (HFrEF). Sacubitril/Valsartan vs. ACEI or ARB was evaluated on Mortality, hospitalizations, quality of life, and exercise tolerance. Sacubitril/valsartan mortality and quality of life benefits over enalapril seen in PARADIGM HF were not corroborated in a review of 11 subsequent randomized comparative trials.
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