Objective: We evaluated the role of sacubitril/valsartan in heart rate variability, T-peak to T-end index, external cell mass, internal cell mass and total body water in elderly patients with heart failure with reduced ejection fraction (HFrEF).
Methods: Eleven elderly patients (9 males; mean age 77 years, range 70-87; 2 females, mean age 60 years, range 50-71) with HFrEF (<35%) were included in this analysis. Four patients presented moderate chronic kidney failure (creatinine clearance [CrCl] 30-59 mL/min) and four patients with diabetes (HbA1c >6.5%). All patients had hypertension and dyspnoea due to HF. Clinical outcomes of this investigation were kidney function, glucose, brain-natriuretic peptide, heart rate variability, T-peak to T-end index and markers of body water composition with bioelectrical impedance analysis (BIA).
Results: One-month therapy with sacubitril/valsartan 24/26 mg/bid was associated with an improved redistribution of body water (extracellular mass: 19.4 ± 3.0 at baseline vs 18.4 ± 2.6 Kg/m at 1 month; p = .001), body weight reduction (81 ± 8 vs 78 ± 8 Kg; p = .002) and improved clinical outcomes (i.e. reduction of dyspnoea, mean duration of symptoms and walking test).
Conclusions: Based on our preliminary results, sacubitril/valsartan could be a new effective approach in the treatment of elderly patients with chronic HFrEF. However, further studies are necessary to confirm these preliminary findings.
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http://dx.doi.org/10.1080/03007995.2019.1576484 | DOI Listing |
Background: The therapeutic management of dementia with Lewy bodies (LBD) is a challenge given the high sensitivity to drugs in this disease. This is particularly sensitive with regard to the management of parkinsonism. In particular, treatment of motor symptoms with levodopa or dopaminergic agonists poses a risk of worsening cognitive and behavioral symptoms.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Centre for Addiction and Mental Health, Toronto, ON, Canada.
Background: Dysregulated GABA/somatostatin (SST) signaling has been implicated in psychiatric and neurodegenerative disorders. The inhibition of excitatory neurons by SST+ interneurons, particularly through α5-containing GABAA receptors (α5-GABAAR), plays a crucial role in mitigating cognitive functions. Previous research demonstrated that an α5-positive allosteric modulator (α5-PAM) mitigates working memory deficits and reverses neuronal atrophy in aged mice.
View Article and Find Full Text PDFBackground: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFBackground: Early-onset Alzheimer's disease (EOAD) associated with amyloid precursor protein (APP) duplications or presenilin (PSEN) variants increases risk of seizures. Targeting epileptiform activity with antiseizure medicine (ASM) administration to AD patients may beneficially attenuate cognitive decline (Vossel et al, JAMA Neurology 2021). However, whether mechanistically distinct ASMs differentially suppress seizures in discrete EOAD models is understudied (Lehmann et al, Neurochem Res 2021).
View Article and Find Full Text PDFBackground: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
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