What does this research mean for the field?

LCZ696 reduces diet-induced atherosclerotic plaque area and vascular inflammation compared to hydralazine in ApoE-deficient mice, but provides no significant difference compared to valsartan alone. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to evaluate the effects of LCZ696 on vascular inflammation and atherosclerosis in apolipoprotein E-deficient mice.

April 25, 2026Open Access

LCZ696, an Angiotensin Receptor-Neprilysin Inhibitor, Attenuates Vascular Inflammation and Atherosclerosis in Apolipoprotein E-deficient Mice

Q: What is the clinical evidence from this study?

Study design: Other. Population: Atherosclerosis and vascular inflammation. Intervention: LCZ696 (sacubitril/valsartan) vs. Hydralazine (10 mg/kg/day) or Valsartan (50 mg/kg/day). Primary outcome: Atherosclerotic lesions in the aortic arch (percentage of Sudan IV-positive area) (p=<0.05).

Key Result

LCZ696 reduced diet-induced atherosclerotic plaque area to 23.6% compared to 33.1% with hydralazine in ApoE-deficient mice, but showed no significant difference compared to valsartan.

Key Points

This research aims to evaluate the effects of LCZ696 on vascular inflammation and atherosclerosis in apolipoprotein E-deficient mice.
Compared LCZ696 to hydralazine and valsartan in treating ApoE-/- mice fed a diet inducing atherosclerosis.
Assessed the progression of atherosclerotic plaques and vascular inflammation.
LCZ696 significantly reduced atherosclerotic plaque progression compared to hydralazine.
No significant difference in outcomes was found between LCZ696 and valsartan.

Structured PICO

Does sacubitril/valsartan reduce atherosclerotic lesion progression and vascular inflammation in ApoE-/- mice compared to hydralazine or valsartan?

Population

Male ApoE-/- mice (C57BL/6J background) fed a Western-type diet from 8 weeks of age. n=13-15 per group.

Intervention

Sacubitril/valsartan 100 mg/kg/day administered by oral gavage once daily for 20 weeks.

Comparator

Valsartan 50 mg/kg/day or hydralazine 10 mg/kg/day administered by oral gavage once daily for 20 weeks.

Outcome

Progression of atherosclerotic lesions (percentage of Sudan IV-positive area in the aortic arch) and vascular inflammation (mRNA expression of inflammatory molecules in the abdominal aorta) at 20 weeks.surrogate

In a mouse model of diet-induced atherosclerosis, sacubitril/valsartan attenuated plaque progression and vascular inflammation compared to a non-RAAS inhibitor (hydralazine), but provided no additional anti-atherosclerotic benefit over valsartan alone.

Main Result

Absolute Event Rate: 23.6% vs 33.1%

p-value: p=<0.05

Limitations

Animal model study, which may not fully translate to human clinical outcomes

Abstract

LCZ696 reduced the progression of diet-induced atherosclerotic plaques and vascular inflammation compared with hydralazine in ApoE-/- mice, but showed no difference compared with the valsartan group. J. Med. Invest. 73 : 116-120, February, 2026.

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Cite This Study

Maeda et al. (Thu,) conducted a other in Atherosclerosis and vascular inflammation. LCZ696 (sacubitril/valsartan) vs. Hydralazine (10 mg/kg/day) or Valsartan (50 mg/kg/day) was evaluated on Atherosclerotic lesions in the aortic arch (percentage of Sudan IV-positive area) (p=<0.05). LCZ696 reduced diet-induced atherosclerotic plaque area to 23.6% compared to 33.1% with hydralazine in ApoE-deficient mice, but showed no significant difference compared to valsartan.

synapsesocial.com/papers/69ec59c688ba6daa22dab735 https://doi.org/https://doi.org/10.2152/jmi.73.116

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