Current Knowledge about the New Drug Firibastat in Arterial Hypertension

Hansen, E. Hjørting; Grimm, Daniela; Wehland, Markus

doi:10.3390/ijms23031459

Cited by 8 publications

(3 citation statements)

References 51 publications

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“…Growing preclinical evidence of the protective effect of APA inhibition in HT led to the development of a first-in-class prodrug, RB150 or Firibastat, which crosses the bloodbrain barrier following oral administration and is cleaved into EC33, an active APA inhibitor. The safety and efficacy of Firibastat in HT patients were confirmed in phase I, IIa, and IIb clinical trials, and the drug is now tested in phase III trials in treatment-resistant HT patients (NCT04857840, NCT04277884) [32,33].…”

Section: The Renin-angiotensin-aldosterone Systemmentioning

confidence: 92%

Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases

2023

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Hypertension (HT) is a modifiable risk factor for life-threatening cardiovascular diseases (CVDs) including coronary artery disease, heart failure, or stroke. Despite significant progress in understanding the pathophysiological mechanisms of the disease, the molecular pathways targeted by HT treatment remain largely unchanged. This warrants the need for finding novel biomarkers, which are causally related to persistent high blood pressure (BP) and may be pharmacologically targeted. Analytical output derived from large-scale biobanks, containing high-throughput genetic and biochemical data, such as OLINK and SomaScan-based proteomics or Nuclear Magnetic Resonance-based metabolomics, as well as novel analytical tools including the Mendelian randomization (MR) approach, enabling genetic causal inference, may create new treatment opportunities for HT and related CVDs. MR analysis may constitute additional evidence for observational studies and facilitate selection of drug targets for clinical testing and has been already used to nominate potentially causal biomarkers for HT and CVDs such as circulating glycine, branched-chain amino acids, lipoprotein(a), insulin-like growth factor 1, or fibronectin 1. Using the MR framework, genetic proxies for targets of already known drugs, such as statins, PCSK9, and ACE inhibitors, may additionally be informative about potential side effects and eventually contribute to more personalized medicine. Finally, genetic causal inference may disentangle independent direct effects of correlated traits such as lipid classes or markers of inflammation on cardiovascular clinical outcomes such as atherosclerosis and HT. While several novel HT-targeting drugs are currently under clinical investigation (e.g. brain renin-angiotensin-aldosterone system inhibitors or endothelin-1 receptor antagonists), analysis of high-throughput proteomic and metabolomic data from well-powered studies may deliver novel druggable molecular targets for HT and associated CVDs.

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Section: The Renin-angiotensin-aldosterone Systemmentioning

confidence: 92%

Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases

2023

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“…Managing normal glycemic levels by employing anti-hyperglycemic drugs helps reduce the risk of microvascular diseases such as retinopathy and nephropathy [59] in the short term while reducing risks for myocardial infarction and stroke [60,61]. In clinical trials, anti-hypertensive treatment, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and calcium channel blockers, have effectively lowered blood pressure [62]. Despite a lot of conventional pharmacotherapy agents having been used for more than two decades, many studies have been conducted extensively in order to provide alternative treatment in the management of CVDs.…”

Section: Cardiovascular Risk Factors and Their Managementmentioning

confidence: 99%

Therapeutic Potential of Hibiscus sabdariffa Linn. in Attenuating Cardiovascular Risk Factors

Sapian,

Ibrahim Mze,

Jubaidi

et al. 2023

Pharmaceuticals

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Cardiovascular diseases (CVDs) represent a broad spectrum of diseases afflicting the heart and blood vessels and remain a major cause of death and disability worldwide. CVD progression is strongly associated with risk factors, including hypertension, hyperglycemia, dyslipidemia, oxidative stress, inflammation, fibrosis, and apoptosis. These risk factors lead to oxidative damage that results in various cardiovascular complications including endothelial dysfunctions, alterations in vascular integrity, the formation of atherosclerosis, as well as incorrigible cardiac remodeling. The use of conventional pharmacological therapy is one of the current preventive measures to control the development of CVDs. However, as undesirable side effects from drug use have become a recent issue, alternative treatment from natural products is being sought in medicinal plants and is gaining interest. Roselle (Hibiscus sabdariffa Linn.) has been reported to contain various bioactive compounds that exert anti-hyperlipidemia, anti-hyperglycemia, anti-hypertension, antioxidative, anti-inflammation, and anti-fibrosis effects. These properties of roselle, especially from its calyx, have relevance to its therapeutic and cardiovascular protection effects in humans. This review summarizes the findings of recent preclinical and clinical studies on roselle as a prophylactic and therapeutic agent in attenuating cardiovascular risk factors and associated mechanisms.

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“…The high prevalence of hypertension as a silent killer is due to hypertension not showing symptoms in the early stages, only emerging after the severe stage has been reached [ 5 ]. Hypertension occurs when the blood pressure (BP) in the arteries rises and forces the heart to pump harder to deliver oxygenated blood to other parts of the body [ 6 ]. Therefore, screening of blood pressure levels is essential for early diagnosis of hypertension to prevent severe complications and to provide the proper medical treatment for the patient [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Classification of Blood Pressure Levels Based on Photoplethysmogram and Electrocardiogram Signals with a Concatenated Convolutional Neural Network

Fuadah

Lim

2022

Diagnostics

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Hypertension is a severe public health issue worldwide that significantly increases the risk of cardiac vascular disease, stroke, brain hemorrhage, and renal dysfunction. Early screening of blood pressure (BP) levels is essential to prevent the dangerous complication associated with hypertension as the leading cause of death. Recent studies have focused on employing photoplethysmograms (PPG) with machine learning to classify BP levels. However, several studies claimed that electrocardiograms (ECG) also strongly correlate with blood pressure. Therefore, we proposed a concatenated convolutional neural network which integrated the features extracted from PPG and ECG signals. This study used the MIMIC III dataset, which provided PPG, ECG, and arterial blood pressure (ABP) signals. A total of 14,298 signal segments were obtained from 221 patients, which were divided into 9150 signals of train data, 2288 signals of validation data, and 2860 signals of test data. In the training process, five-fold cross-validation was applied to select the best model with the highest classification performance. The proposed concatenated CNN architecture using PPG and ECG obtained the highest test accuracy of 94.56–95.15% with a 95% confidence interval in classifying BP levels into hypotension, normotension, prehypertension, hypertension stage 1, and hypertension stage 2. The result shows that the proposed method is a promising solution to categorize BP levels effectively, assisting medical personnel in making a clinical diagnosis.

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Current Knowledge about the New Drug Firibastat in Arterial Hypertension

Cited by 8 publications

References 51 publications

Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases

Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases

Therapeutic Potential of Hibiscus sabdariffa Linn. in Attenuating Cardiovascular Risk Factors

Classification of Blood Pressure Levels Based on Photoplethysmogram and Electrocardiogram Signals with a Concatenated Convolutional Neural Network

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