aliskiren / Generic mfg. - LARVOL DELTA

Protective effect of aliskiren on renal injury in AGT-REN double transgenic hypertensive mice (PubMed, Sheng Li Xue Bao) - "However, aliskiren reduced blood pressure in dTH mice, improved renal structure and renal function, reduced Ang II and Ang-(1-7) levels in serum and renal tissue, reduced the expression of ACE and AT1R in renal tissue, increased the expression of ACE2 and MasR in renal tissue, and decreased the above levels of oxidative stress indexes in dTH mice. These results suggest that aliskiren may play a protective role in hypertensive renal injury by regulating the balance between ACE-Ang II-AT1R and ACE2-Ang-(1-7)-MasR axes and inhibiting oxidative stress."

Journal • Preclinical • Cardiovascular • Glomerulonephritis • Hypertension • Renal Disease • ACE2 • NOX4

Drug repurposing for renin inhibition: identifying panobinostat for hypertension management. (PubMed, Mol Divers) - "The in vitro Elisa-based assay revealed Panobinostat has the potential to inhibit the renin enzyme at the half-maximal concentration (IC50) of 201.27 nM, while standard renin inhibitor Aliskiren portrayed an IC50 of 162.22 nM. The comparable potency to clinical renin inhibitors presents this HDAC inhibitor as a dual-functioning ligand. The findings are significant and well correlated with the plethora of evidence suggesting the role of HDACs in regulating RAAS and cardiovascular functions via the post-translational level modulation of chromatins' structures and functions."

Journal • Cardiovascular • Hypertension • Renal Disease

Study on the Safety and Efficacy of Aliskiren/Amlodipine Tablets in Patients with Primary Hypertension (ChiCTR) - P=N/A | N=200 | Not yet recruiting | Sponsor: Tianjin Medical University General Hospital; Tianjin Medical University General Hospital

New trial • Cardiovascular • Hypertension

Angiotensinogen and C3 compete for renin-induced complement activation. (PubMed, Front Immunol) - "C3a was generated at a similar rate to that by C3 convertase, and C3 cleavage was inhibited by the renin inhibitor aliskiren...The results suggest that renin cleaves C3 but angiotensinogen is its preferred substrate. The interaction between renin and C3 may gain importance in the kidney where renin concentrations are considerably higher than in the circulation and when the primary substrate, angiotensinogen, is cleaved and thereby depleted."

Journal

Pharmacokinetic Interactions of Fruit Juices with Antihypertensive Drugs in Humans: A Systematic Review and Meta-analyses. (PubMed, Complement Ther Med) - "Co-administration of fruit juice with antihypertensive drugs can result in an increase or decrease in drugs' bioavailability, depending on the drugs' metabolism route and involvement of transporters. Though further studies are needed to confirm clinical relevance in hypertensive patients, it is advised to avoid co-consumption of fruit juice with drugs showing significant changes in pharmacokinetic parameters to prevent subtherapeutic or supratherapeutic effects."

Journal • PK/PD data • Review

In vitro identification of decreased function genetic variants of ABCB1. (PubMed, Eur J Pharm Sci) - "These cells were then used to prepare membrane vesicles, which were used to study N-methyl-quinidine (NMQ) and aliskiren transport...In addition, R580P and A980P decreased the transport of both substrates to ≤50%, while S795C affected only NMQ transport. Based on our results, carriers of the C717Y, L305P, or V907F variants may experience altered distribution and exposure of ABCB1 substrate drugs."

Journal • Preclinical • ABCB1

Renin inhibitors versus angiotensin receptor blockers for primary hypertension. (PubMed, Cochrane Database Syst Rev) - "The available RCT evidence suggests little to no difference between renin inhibitors and ARBs in terms of mortality, SAE, WDAE, adverse events, and blood pressure in people with mild primary hypertension. The evidence was derived from short-term trials with a limited occurrence of morbidity outcomes, leaving any potential differences unknown. Larger RCTs of longer duration with a wider range of participants and a focus on cardiovascular outcomes are needed."

Clinical • Journal • Review • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Heart Failure • Hypertension • Myocardial Infarction • Nephrology • Renal Disease

Amlodipine-Associated Angioedema: An Integrated Pharmacovigilance Assessment Using Disproportionality and Interaction Analysis and Case Reviews. (PubMed, J Clin Med) - "Significant safety signals were detected for amlodipine alone and in combination with aliskiren, specific ACE inhibitors (quinapril, benazepril, trandolapril, fosinopril, perindopril), and certain ARBs (candesartan, losartan). While these results should not discourage appropriate clinical use, they emphasize the importance of monitoring for angioedema, particularly during therapy initiation. The findings from this study need to be validated in prospective studies for further elucidation of the underlying mechanisms."

Adverse events • Journal • Cardiovascular • Hypertension

Comparison of the effectiveness of aliskiren and ramipril for the management of hypertension: A systematic review and meta-analysis. (PubMed, Hipertens Riesgo Vasc) - "Aliskiren provides, in the short term, a slight improvement in BP in non-elderly hypertensive patients without diabetes or previous cardio-cerebrovascular disease."

Clinical • Journal • Retrospective data • Review • Cardiovascular • CNS Disorders • Diabetes • Hypertension • Metabolic Disorders • Vascular Neurology

Non-Inferiority Study of Aliskiren vs Losartan in the Treatment of Hypertension With Hyperuricemia (clinicaltrials.gov) - P4 | N=66 | Completed | Sponsor: Hansung University

Head-to-Head • New P4 trial • Cardiovascular • Hypertension

Kidney and cardiac biomarkers and risk of adverse kidney outcomes in patients with type 2 diabetes and kidney disease, cardiovascular disease, or both (AHA 2024) - "However, the discriminatory ability of these biomarkers in isolation and in combination is less clear.Methods We examined data from participants in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) with available baseline measurements (n=5,597)...The combined 4-biomarker model C-statistic was 0.847, which increased to 0.865 with the addition of clinical covariates (Table 1).ConclusionAmong participants of ALTITUDE, higher UACR was the most important prognostic biomarker of future adverse kidney events, beyond that of a multivariable clinical model. The addition of eGFR, hsTnT, and NT-proBNP to UACR marginally improved model discrimination, with further improvement by adding clinical variables."

Adverse events • Biomarker • Clinical • Cardiovascular • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Successful treatment of severe renal failure caused by malignant hypertension using a combination of renin-angiotensin-aldosterone system inhibitors: a case report. (PubMed, CEN Case Rep) - "This report presents a case of MHT complicated with renal insufficiency (creatinine 3.93 mg/dL) and massive proteinuria, in which antihypertensive therapy, including an angiotensin receptor blocker, aliskiren, and spironolactone, normalized blood pressure (BP) and preserved renal function. This case of renal failure induced by MHT was successfully treated with a combination of RAAS inhibitors during the acute phase. The controlled BP and improved renal function in this patient suggest that adequate suppression of the RAAS cascade during the acute phase is potentially effective in terms of breaking the vicious cycle of MHT with hyperreninemia."

Journal • Cardiovascular • Hypertension • Nephrology • Renal Disease

Spontaneous and evoked angiotensin II sniffer cell activity in the lamina terminalis in vitro. (PubMed, Am J Physiol Regul Integr Comp Physiol) - "Bath application of tetrodotoxin (1 µM) significantly attenuated spontaneous events while abolishing evoked sniffer cell activity...Pharmacological experiments indicate that ANG II release is largely both renin (aliskiren 10 µM) and ACE-1 (captopril 100 µM) dependent...Lastly, these studies demonstrate that increases in ANG II release are observed following 7 days of chronic intermittent hypoxia. These studies suggest the existence of a tissue-specific RAS in the brain that involves canonical and alternative ANG II synthetic pathways and is upregulated in an animal model of sleep apnea."

Journal • Preclinical • Cardiovascular • Hypertension • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy. (PubMed, J Am Heart Assoc) - P3 | "Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum."

Biomarker • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • B2M • EGF • SVEP1 • TIMP1

Evaluation of a Renin Inhibitor, Aliskiren, Compared to Enalapril, in C3 Glomerulopathy (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Region Skane | Trial completion date: Dec 2024 ➔ Dec 2029 | Trial primary completion date: Dec 2024 ➔ Dec 2029

Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease

Machine learning does not improve risk prediction in heart failure in comparison to the PREDICT-HF model: derivation and validation in PARADIGM-HF and ATMOSPHERE (HEART FAILURE 2024) - " We used the two trials that were used to develop the PREDICT-HF risk model, Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF), the training set, and Aliskiren Trial to Minimize OutcomeS in Patients with HEart FailuRE trial (ATMOSPHERE), the testing set... Although ML based models improved risk prediction when derived in PARADIGM-HF, when tested in ATMOSPHERE their performance fell and did not substantially improve the prediction obtained from the previously validated, and more consistent Cox model in PREDICT-HF."

Machine learning • Cardiovascular • Congestive Heart Failure • Heart Failure

Natriuretic peptide system in hypertension: current understandings of its regulation, targeted therapies and future challenges. (PubMed, Eur J Pharmacol) - "More importantly, it will shed light on recent developments in NPS-targeted therapies, such as M-atrial peptides, and their latest combinations with RAAS modulators, such as S086 and sacubitril-aliskiren. These insights will aid in the development of effective therapies to break the vicious cycle of high blood pressure during hypertension, ultimately addressing the expanding global heart failure pandemic."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension

Drugs for hypertension. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Review • Cardiovascular • Hypertension

Prediction of new-onset heart failure in patients with type 2 diabetes derived from ALTITUDE and CANVAS. (PubMed, Diabetes Obes Metab) - "In patients with T2D, higher NT-proBNP level, TnT level and BMI are independent and externally validated predictors of new-onset HF, including patients using an SGLT2 inhibitor. This newly developed model may identify patients at high risk of new-onset HF, contributing to early recognition and possibly prevention."

Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Renin-Angiotensin System Inhibitors Suppress the Growth of Leukemia Cells. (PubMed, Anticancer Res) - "RAS inhibitors can be repurposed as molecular-targeted drugs for leukemia. However, the concentrations of the inhibitors were much higher than those in the plasma of patients with hypertension. Therefore, further investigation is required for their clinical use."

Journal • Acute Myelogenous Leukemia • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Hypertension • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CASP3 • MYC • NOTCH1

Aliskiren-Loaded Nanoparticles Downregulate (Pro)renin Receptor and ACE Gene Expression in the Heart of Spontaneously Hypertensive Rats: Effect on NADPH Oxidase. (PubMed, Int J Mol Sci) - "We hypothesize that aliskiren-loaded nanoparticle-mediated downregulation of Atp6ap2 and ACE may contribute to a decrease in ROS generation with beneficial effects in the heart. Moreover, polymeric nanoparticles may represent a promising tool for targeted delivery of aliskiren."

Journal • Preclinical • Cardiovascular • Hypertension • ATP6AP2

Effective Management of Hypertensive Emergencies with Aliskiren Treatment in a Patient Before and After Introducing Hemodialysis Secondary to Scleroderma Renal Crisis-like Condition Under Corticosteroid Treatment for Sjögren Syndrome-associated Multiple Mononeuropathy. (PubMed, Intern Med) - "Aliskiren appears to be effective in managing hypertensive heart failure in patients with SRC. Nevertheless, hemodialysis remained necessary in our case, and whether or not aliskiren can restore the renal function is unclear."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Hypotension • Immunology • Pain • Scleroderma • Sjogren's Syndrome • Systemic Sclerosis

Identification of novel compounds and repurposing of FDA drugs for 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme of Plasmodium falciparum to combat malaria resistance. (PubMed, Int J Biol Macromol) - "Following our computational pipeline, we found five novel ZINC20 compounds (Z-2, Z-3, Z-10, Z-13, and Z-14) and three FDA drugs (Aliskiren, Ceftolozane, and Ombitasvir) that showed striking docking energy (ranging from -8.405 to -10.834 kcal/mol), and strong interactions with key binding site residues (Ser-269, Ser-270, Ser-306, Asn-311, Lys-312, and Met-360) of PfIspC. Notably, the binding free energy estimation confirmed high binding affinity (varied from -11.68 to -33.16 kcal/mol) of these compounds for PfIspC. Our findings could contribute to the ongoing efforts in combating malaria and invite experimental-lab researchers for validation."

Journal • Infectious Disease • Malaria

Development and Validation of a New Hierarchical Composite Endpoint for Clinical Trials of Kidney Disease Progression. (PubMed, J Am Soc Nephrol) - "In seven major kidney clinical trials, the WO and HR provided similar direction of treatment effect estimates with smaller HRs associated with larger WOs. The prioritization of clinical outcomes and inclusion of broader composite end points makes the HCE an attractive alternative to the established kidney end point."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Renin and renin blockade have no role in complement activity. (PubMed, Kidney Int) - "Third, aliskiren, a renin inhibitor, does not block abnormal complement activity introduced by nephritic factors in the fluid phase...And seventh, molecular modeling and docking place C3 in the active site of renin in a position that is not consistent with a productive ground state complex for catalytic hydrolysis. Thus, our study does not support a role for renin in the activation of complement."

Journal • Atypical Hemolytic Uremic Syndrome • Complement-mediated Rare Disorders • Glomerulonephritis • Nephrology