Impact of renin-angiotensin system-targeting antihypertensive drugs on treatment of Alzheimer's disease: a meta-analysis

Ye, Rong; Hu, Yibo; Yao, Angela; Yang, Ying; Shi, Yonghong; Jiang, Yu-Gang; Zhang, J.

doi:10.1111/ijcp.12626

Cited by 32 publications

(17 citation statements)

References 36 publications

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“…It is noteworthy that angiotensin II itself can contribute to the development of Alzheimer's disease . Despite experimental evidence for a role of ACE in beta‐amyloid clearance, both ARBs and ACE inhibitors have been reported to have favourable effects on beta‐amyloid deposition and cognition, with the effects of ARBs being greater than those of ACE inhibitors . It may therefore not be surprising that the simultaneous inhibition of neprilysin and the angiotensin receptor has not led to the accumulation of pathogenetic forms of amyloid in humans .…”

Section: Safety Of Neprilysin Inhibitionmentioning

confidence: 99%

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA

Packer

2016

European J of Heart Fail

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Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB.

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Section: Safety Of Neprilysin Inhibitionmentioning

confidence: 99%

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA

Packer

2016

European J of Heart Fail

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“…The ten-best combinations of the eleven drugs that excluded drugs acting on the brain and/or psychological level included NSAID, anticoagulant, lipid-lowering, and antihypertensive drugs, as well as estrogen/progestin. Drugs from all of these categories have been shown to reduce AD risk, however they all show disappointing results when used singly in clinical trials [33][34][35][36][37][38][39][40][41][42][43][44][45]. The use of combinations of these and other drugs remains an attractive option [7][8][9][10][11].…”

Section: Discussionmentioning

confidence: 99%

Predicting the potency of anti-Alzheimer drug combinations using machine learning

Anastasio

2020

Preprint

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BACKGROUND: Clinical trials of single drugs for the treatment of Alzheimer Disease (AD) have been notoriously unsuccessful. Combinations of repurposed drugs could provide effective treatments for AD.The challenge is to identify potentially potent combinations.OBJECTIVE: To use machine learning (ML) to extract the knowledge from two leading AD databases, and then use the machine to predict which combinations of the drugs in common between the two databases would be the most effective as treatments for AD.METHODS: Three-layered neural networks (NNs) having compound, gated units in their internal layer were trained using ML to predict the cognitive scores of participants in either database, given the other data fields including age, demographic variables, comorbidities, and drugs taken. RESULTS:The predictions from the separately trained NNs were strongly correlated. The best drug combinations, jointed determined from both sets of predictions, were high in NSAID, anticoagulant, lipid-lowering, and antihypertensive drugs, and female hormones. CONCLUSION:The results suggest that AD, as a multifactorial disorder, could be effectively treated using a combination of repurposed drugs.

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“…Recent brain studies of BMS patients with functional magnetic resonance imaging (fMRI) have shown hypofunctional activity in the CNS of patients, especially in the hippocampus and medial prefrontal cortex (Khan, Keaser, Meiller, & Seminowicz, 2014). Because of the discovery that the use of some antihypertensives, such as ARBs, may have a negative association with other CNS pathoses, such as Alzheimer's disease (Ye et al, 2015), we can claim that these medications may play a protective role against neurodegenerative processes linked to ischaemia or reduced function of blood vessels in the brain (Van Agtmaal, Houben, Pouwer, Stehouwer, & Schram, 2017;Direk et al, 2016).…”

Section: Frequency Of Distributionmentioning

confidence: 99%

Is there an association between drugs and burning mouth syndrome? A case–control study

et al. 2019

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Objective The purpose of this case–control study was to compare the pharmacological anamnesis collected from a group of 150 burning mouth syndrome (BMS) patients with that of a control group of 150 patients matched for age and sex. Materials and Methods The patients' medical histories were reviewed, and data on drug therapy were collected. Drugs were classified on the basis of pharmacological effects; the classes were antihypertensives (i.e., ACE inhibitors/ARBs, calcium antagonists, diuretics and beta‐blockers), antiaggregants, anticoagulants, antidiabetics, vitamin D integrators, bisphosphonates, psychotropics (i.e., anxiolytics and antidepressants), gastroprotectors, statins, thyroid hormone substitutes, corticosteroids and immunosuppressants. Results The BMS patients and the controls were matched for age (mean age: 69 years) and sex (128 females and 22 males). Antihypertensives, especially ACE inhibitors/ARBs (OR = 0.37, CI: 0.22–0.63, p = 0.0002) and beta‐blockers (OR = 0.36, CI: 0.19–0.68 p = 002), revealed an inverse association with the presence of BMS, whereas anxiolytics (OR = 3.78, CI: 2.12–6.75 p < 0.0001), but neither antidepressants nor antipsychotics, were significantly associated with BMS. There were no correlations with other drug classes. Conclusion Our study highlighted that ACE inhibitors, ARBs and beta‐blockers were in inverse relation to BMS and found that anxiolytics, but neither antidepressants nor antipsychotics, were linked to the presence of the syndrome.

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Impact of renin-angiotensin system-targeting antihypertensive drugs on treatment of Alzheimer's disease: a meta-analysis

Abstract: Renin-angiotensin system-targeting antihypertensive drugs may be a potential treatment for reducing the incidence and progression of AD. Further studies on RAS-targeting antihypertensive drugs, especially large randomised clinical trials, should be conducted in the future.

Cited by 32 publications

References 36 publications

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA

Predicting the potency of anti-Alzheimer drug combinations using machine learning

Is there an association between drugs and burning mouth syndrome? A case–control study

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