Why the study?
The mechanism of how sacubitril/valsartan improves outcomes in HFrEF remains incompletely understood.
Does sacubitril/valsartan improve endothelial function as measured by flow-mediated vasodilation compared to valsartan alone in patients with symptomatic heart failure with reduced ejection fraction?
Does sacubitril/valsartan improve endothelial function as measured by flow-mediated vasodilation compared to valsartan alone in patients with symptomatic heart failure with reduced ejection fraction?
Three months of treatment with sacubitril/valsartan significantly lowered blood pressure and retinal venular dilatation in stable HFrEF patients compared to valsartan alone, but did not improve brachial artery endothelial function or arterial stiffness, suggesting its clinical benefits are not mediated by peripheral endothelial improvements.
Answers are grounded in this paper and cite their sources.
No added benefit on endothelial function or arterial stiffness in stable HFrEF; challenges expectations of superior vascular effects versus valsartan.
Background: The mechanism of how sacubitril/valsartan improves outcomes in heart failure with reduced ejection fraction (HFrEF) is still incompletely understood. Objectives: The aim of this trial was to delineate the effects of sacubitril/valsartan on endothelial function, retinal microvascular function, and arterial stiffness in HFrEF. Methods: This double-blind controlled trial randomized 79 stable HFrEF patients with NYHA class II-IV on guideline-recommended therapy (mean age: 59.4 ± 12 years, left ventricular ejection fraction: 30% ± 7%) to sacubitril/valsartan or valsartan alone for 3 months. The primary endpoint was flow-mediated vasodilation (FMD). Secondary outcomes included flicker-induced dilatation of retinal arterioles and venules (FIDv), retinal arteriovenous ratio, and surrogate markers of arterial stiffness (pulse wave velocity and augmentation index). There were numerically fewer serious adverse events with sacubitril/valsartan versus valsartan alone. Conclusions: In this randomized double-blind clinical trial addressing mechanisms, sacubitril/valsartan lowered blood pressure and flicker-induced dilatation of retinal venules in patients with symptomatic HFrEF but did not improve endothelial function, retinal microvascular function, or arterial stiffness compared to valsartan monotherapy. (Differential Vascular and Endocrine Effects of Valsartan/Sacubitril in Heart Failure With Reduced Ejection Fraction [VASCEND]; NCT03168568).
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Nägele et al. (2024) studied this question.
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