aliskiren / Generic mfg. - LARVOL DELTA

Structure-Based Design and In Silico Evaluation of a Lipophilic Cyclooctanoyl- Derivative as a Renin Inhibitor: Lessons from Withdrawn Aliskiren. (PubMed, Int J Mol Sci) - "The MD analysis (200 ns) demonstrated that the inhibitor is anchored via a dual stabilization mechanism: hydrophobic enclosure coupled with persistent ionic interactions. These integrative in silico results highlight the potential of this derivative to overcome Aliskiren's pharmacological shortcomings, providing a strong computational rationale for experimental validation and underscoring the role of structure-based drug design in antihypertensive drug discovery."

Journal • Cardiovascular • Hypertension

Clinician survey for the management of central venous catheter-related bloodstream infection: Catheter retention versus replacement. (PubMed, J Assoc Med Microbiol Infect Dis Can) - "For peripherally inserted central catheter-related BSI, most favoured CVC replacement, although there was variability across pathogens (Candida spp 100%, Staphlococcus aureus 99%; Pseudomonas aeruginosa 94%; Enterococcus spp 75%; Enterobacterales 66%; coagulase-negative staphylococci 58%)...For each combination of pathogen and CVC type, a majority (>50%) of participants reported willingness to enrol patients into an RCT comparing CVC replacement versus retention; the only exceptions below 50% were S. aureus (44%) and Candida spp (44%) CRBSIs from short-term non-tunnelled CVCs. There is heterogeneity in CVC management practices and stated equipoise for an RCT comparing management approaches for a range of CVC types, BSI sources, and pathogens."

Journal • Infectious Disease

Effects of Inhibitors of the Activity of the Circulating Renin-Angiotensin System on the Growth and Proliferation of Endometrial Cancer Cells. (PubMed, Int J Mol Sci) - "We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs."

Journal • Endometrial Cancer • Oncology • Solid Tumor

Prevalence of gastrointestinal parasites and their associated risk factors in sheep raised at high and low altitudes in Swat, Pakistan. (PubMed, Open Vet J) - "The number of eggs per gram for Haemonchus spp was 50-1,600epg, Trichuris spp 50-300epg, Taenia spp 50-250epg, Fasciola spp 50-200epg, Moniezia spp 50-150epg, Paramphistomum spp 100-150epg, Dicrocoelium 100-150epg, Filicollis spp 50-150epg, Eimeria spp (oocysts) 50-100epg, and Nematodirus spp 50-100epg, were detected. The current study evidenced higher rates of helminth parasitic infection that can be prevented by ensuring antihelminthic treatments for the sheep population at different intervals."

Journal • Gastrointestinal Disorder • Infectious Disease

Resistant Hypertension in ANCA-Associated Vasculitis: Role for Aliskiren? (KIDNEY WEEK 2025) - "Despite receiving cyclophosphamide and methylprednisolone, he remained dialysis-dependent and was referred for renal transplant. He had multiple hypertensive emergency admissions despite a multi-drug regimen with nifedipine, telmisartan, carvedilol, eplerenone, clonidine, and hydralazine, and dry weight optimization...Studies are warranted to compare DRI efficacy against standard antihypertensives in similar clinical scenarios. The views expressed in this abstract are those of the author(s) and do not necessarily reflect the official policy of the Department of Defense or the U.S. Government."

ANCA Vasculitis • Cardiovascular • Glomerulonephritis • Hypertension • Inflammation • Lupus Nephritis • Nephrology • Renal Disease • Vasculitis • MPO

Potential role of Aliskiren in cancer modulation compared to other Renin-Angiotensin inhibitors: an in-depth review. (PubMed, Eur J Pharmacol) - "While the oncogenic effects of ACEi and ARBs on cancer remain inconclusive, Aliskiren emerges as an antihypertensive drug potentially able to interfere with pro-oncogenic signaling. Nonetheless, its limited evidence base underscores the urgent need for well-designed prospective studies to clarify the differential oncologic impact of various RASi classes across populations. Indeed, cancer patients undergoing long-term RASi deserve close monitoring and multidisciplinary approach for assessment of personalized therapy."

Journal • Review • Cachexia • Cardiovascular • Hypertension • Lung Cancer • Oncology • Renal Disease • Solid Tumor

Prorenin in Hepatic Stellate Cell Extracellular Vesicles Induces Platelet-Dependent Thrombin Formation and Release of Profibrotic TGF-β. (PubMed, FASEB J) - "The aspartyl protease inhibitor pepstatin, or specific inhibitors Aliskiren and VTP23999 of the aspartyl protease renin suppressed HSC EV-induced platelet activation, as did siRNA knockdown of prorenin...This TGF-β stimulated the LX-2 cell TGFbR1 receptor, Smad phosphorylation, and profibrotic protein expression. We identify hitherto undiscovered pathways by which platelet and HSC interaction stimulates thrombosis through prorenin activation and show intrahepatic platelets are positioned to stimulate fibrotic protein deposition in a model of hepatic fibrosis."

Journal • Cardiovascular • Fibrosis • Hematological Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Thrombosis • TGFB1 • TGFBR1

Structure-based drug design; Computational strategies in drug discovery; Antihypertensive agents; Antiviral drugs; Molecular docking; QSAR; Pharmacological insights. (PubMed, Comput Biol Chem) - "This review meticulously examines the development, design, and pharmacological assessment of both well known antiviral and antihypertensive medications all time employing new chemical techniques and structure-based drug design to design and synthesize vital therapeutic entities such as aliskiren (renin inhibitor), captopril (a2-ACE-Inhibitor), dorzolamide (inhibitor of carbonic anhydrase) the review demonstrates initial steps regarding the significance of stereoselective synthesis, metal chelating pharmacophores, and rational molecular properties. More importantly, protease inhibitors (i.e., saquinavir, ritonavir, indinavir, amprenavir, etc.) and more contemporary agents (i.e., oseltamivir, nirmatrelvir/ritonavir (Paxlovid), etc.) were identified in the review and form a basis of advancement in antiviral therapy...In conclusion, this review highlights the transformative power of interdisciplinary approaches, including structure-based design, computational modeling, and..."

Journal • Review • Cardiovascular • Infectious Disease

Lkb1 Downregulation Links PVAT Remodeling to Aortic Dilation or Aneurysm. (PubMed, Circ Res) - "In this study, we generated tamoxifen-inducible Lkb1flox/flox;Pdgfrα-CreERT2, Lkb1flox/flox;Pdgfrβ-CreERT2, and Lkb1flox/flox;Myh11-CreERT2 mice to investigate the role of Lkb1 in PVAT and related vessel function...Most importantly, treatment with either renin inhibitor aliskiren or Ang II receptor blocker valsartan rescues vascular smooth muscle cell phenotypic switching and aortic dilation in Lkb1flox/flox;Pdgfrα-CreERT2 mice. Our work strongly suggests that Lkb1 deficiency in PVAT drives vascular smooth muscle cell phenotypic switching and aortic dilation and aneurysm formation. Lkb1, via its regulation of renin-angiotensin system in PVAT, maintains vessel homeostasis."

Journal • Cardiovascular • Oncology • PDGFRA • PDGFRB • STK11

Translating Basic Science to Clinical Applications: A Narrative Review of Repurposed Pharmacological Agents in Preclinical Models of Diabetic Neuropathy. (PubMed, Biomedicines) - "A wide array of repurposed drugs-including antidiabetics (metformin, empagliflozin, gliclazide, semaglutide, and pioglitazone), antihypertensives (amlodipine, telmisartan, aliskiren, and rilmenidine), lipid-lowering agents (atorvastatin and alirocumab), anticonvulsants (topiramate and retigabine), antioxidant and neuroprotective agents (melatonin), and muscarinic receptor antagonists (pirenzepine, oxybutynin, and atropine)-have shown promising results in rodent models, reducing neuropathic pain behaviors and modulating underlying disease mechanisms. By bridging basic mechanistic insights with pharmacological interventions, this review aims to support translational progress toward mechanism-based therapies for DN."

Journal • Preclinical • Review • Diabetic Neuropathy • Inflammation • Neuralgia • Pain

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