Why the study?
Sacubitril/valsartan reduces cardiovascular death and hospitalizations in HFrEF, and this review aimed to assess its clinical efficacy on physical exercise capacity and cardiopulmonary parameters.
Does sacubitril/valsartan improve physical exercise capacity and cardiopulmonary parameters compared to active standard therapy in adults with HFrEF?
Does sacubitril/valsartan improve physical exercise capacity and cardiopulmonary parameters compared to active standard therapy in adults with HFrEF?
Answers are grounded in this paper and cite their sources.
This narrative review demonstrates that while real-world observational studies show improvements in exercise tolerance and CPET parameters after initiating sacubitril/valsartan in HFrEF patients, randomized controlled trials have not consistently established its superiority over active standard therapy (like enalapril) for objective exercise capacity.
Background Heart failure is a chronic disease placing a huge burden on patients through drastically reduced quality of life and exercise intolerance. Sacubitril/valsartan, the first angiotensin receptor-neprilysin inhibitor, has proven its efficacy in reducing cardiovascular death and hospitalizations, becoming a standard in heart failure with reduced ejection fraction (HFrEF) pharmacotherapy. Aim The aim of this narrative literature review is to assess the clinical efficacy of sacubitril/valsartan on physical exercise capacity and cardiopulmonary parameters in patients with HFrEF. Materials and Methods A literature search was conducted using PubMed and Google Scholar databases, including randomized controlled trials comparing sacubitril/valsartan with standard therapy, as well as observational studies utilizing real-world data. These studies assessed improvement in cardiopulmonary exercise testing parameters (peak VO2, VE/VCO2 slope), 6-minute walk test and New York Heart Association (NYHA) functional class. Results Several uncontrolled observational studies reported improvements in exercise capacity and NYHA functional class during sacubitril/valsartan therapy, although findings varied across studies and outcomes. However, most randomized controlled trials did not demonstrate statistically significant superiority over active standard therapy in the functional outcomes assessed. Greater improvements were reported among patients reaching maximum target doses, although these patients typically had better baseline clinical status. Conclusions Observational findings suggest potential improvements in exercise tolerance and cardiorespiratory fitness in patients with HFrEF during sacubitril/valsartan therapy. However, superiority over active standard therapy in objective exercise capacity has not been consistently established in randomized controlled trials.
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Górecki et al. (2026) conducted a review in Heart failure with reduced ejection fraction (HFrEF) (n=2,049). Sacubitril/valsartan vs. Standard pharmacotherapy (most commonly enalapril) or baseline pre-treatment status was evaluated on Exercise capacity and functional status (Peak VO2, VE/VCO2 slope, 6-minute walk test distance, and NYHA functional class).
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