JW Pharmaceutical · AGTR1 · Small Molecule
pitavastatin + valsartan is a small molecule developed by JW Pharmaceutical. It is approved for therapeutic indications via oral (po).
| Brand Names | Livalsartan, Livasartan |
| Company | JW Pharmaceutical |
| Drug Class | Small Molecule |
| Molecular Target | AGTR1, HMGCR |
| Route | Oral (PO) |
| Status | Approved |
pitavastatin + valsartan acts on 2 molecular targets:
| AGTR1 | angiotensin II receptor type 1 (HAT1R, AT1) |
| HMGCR | 3-hydroxy-3-methylglutaryl-CoA reductase (LDLCQ3, LGMDR28) |
pitavastatin + valsartan is developed for 2 unique indications across 2 therapeutic areas.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Metabolism and nutrition disorders | Hypercholesterolaemia | ✓ Approved |
| Vascular disorders | Hypertension | ✓ Approved |
Zhao Ying Y
Stefani Sara S, Silva Gustavo Jose Justo GJJ, Cardinali Martina Alunni MA, Parvan Reza R et al.
Cardiorenal syndrome (CRS) involves complex and spatially heterogeneous remodeling in both cardiac and renal tissues. Conventional histological and biochemical assays rely on labeling or lack direct molecular specificity, limiting their ability to capture compartment-specific remodeling. Analytical approaches that resolve localized biochemical alterations are essential to advance mechanistic insight into heart-kidney interactions. Here, Fourier-transform infrared (FTIR) micro-imaging was applied to left ventricular and renal tissues from a rat model of heart-kidney interaction, in which unilateral nephrectomy induced renal stress prior to cardiac ischemia-reperfusion injury. To address tissue heterogeneity, an analytical workflow was implemented in which unsupervised hierarchical clustering segmented spectrally homogeneous regions, followed by principal component analysis, to identify spectral markers associated of disease-related biochemical alterations. This strategy enabled identification of spatially localized spectral variations associated with disease progression. Distinct spectral signatures of tissue remodeling were identified in both organs. Cardiac perivascular regions exhibited pronounced alterations in bands at 1040, 1202, and 1232 cm-1, while renal medullary compartments displayed disease-associated variations at 1313 and 1396 cm-1 following nephrectomy. Several spectral features correlated with independent biological measures, including histologically quantified fibrosis, urinary protein excretion, and left ventricular mass. Treatment-associated spectral modulation was also observed, with animals receiving Sacubitril/Valsartan exhibited spectral intensities below pathological thresholds for the main cardiac markers, indicating partial normalization of disease-associated spectral alterations. These findings demonstrate that spatially resolved FTIR spectroscopic imaging can identify compartment-specific spectral signatures of disease progression and treatment response in experimental heart-kidney interaction.
Rabie Mostafa A MA, Rahmo Rania M RM, El Magdoub Hekmat M HM, Hamdy Nadia M NM et al.
Multiple sclerosis (MS) is a debilitating neuroinflammatory disease frequently associated with cognitive impairment. Recent research suggests that targeting the renin-angiotensin system (RAS) may offer a promising therapeutic strategy for alleviating cognitive deficits in neurodegenerative disorders. This study aimed to explore the interactions between valsartan (VAL), an angiotensin II receptor antagonist, ACE2/Ang 1-7/MasR signaling, and PI3K/Akt/CREB/BDNF pathway in preserving cognitive function using an experimental autoimmune encephalomyelitis (EAE) mouse model. EAE was induced in mice through spinal cord homogenate, leading to motor and cognitive impairments that mimic those observed in MS patients. In addition, comprehensive bioinformatics and chemo-bioinformatics analyses were conducted. Oral administration of VAL (40 mg/kg/day) significantly ameliorated EAE-induced cognitive deficit in spatial and learning memory as evidenced by improved performance in the novel object recognition (NOR) and Morris water maze (MWM), along with a reduction in EAE clinical scoring. Histological analysis further revealed that VAL treatment mitigated EAE-induced demyelination in the corpus callosum. Mechanistically, VAL activated ACE2/Ang 1-7/MasR signaling pathway, stimulating the p-PI3K/p-Akt/p-CREB axis, and consequently elevating BDNF, its receptor TrkB and synapsin, thereby establishing a cycle of neuroprotection. Furthermore, VAL mitigated EAE-induced neuroinflammation by reducing p-NFκB p65, TNF-α and IL-6 contents, while restoring redox balance by enhancing SOD and GPx activities, elevating GSH content and reducing MDA content. Collectively, these findings highlight the potential of VAL in preserving cognitive function in EAE by modulating key neuroprotective and anti-inflammatory pathways, offering valuable insights into novel therapeutic strategies for MS and related neuroinflammatory disorders. These conclusions are further supported by complementary bioinformatics analyses.
Xu Guangsen G, Wang Guiyun G, Fang Yihan Y, Dong Lingjia L et al.
The arachidonic acid (AA) metabolic cascade plays important roles across multiple pathological conditions; however, the contribution of AA-derived lipid metabolism to myocardial infarction (MI) remains incompletely understood. Here, we combined targeted oxylipidomics, experimental and clinical MI analyses, transcriptomic integration, and mechanistic studies to investigate cytochrome P450-2E1 (CYP2E1)-associated metabolic remodeling during MI. Oxylipidomic profiling identified 19-hydroxyeicosatetraenoic acid (19-HETE) as a prominently elevated AA-derived metabolite in experimental MI and linked to impaired cardiac function in clinical MI. Mechanistically, we found that exogenous 19-HETE aggravated oxidative stress and apoptosis in cardiomyocytes, whereas pharmacological inhibition of leukotriene B4 receptor 2 (BLT2) partially attenuated these effects, supporting BLT2-related signaling involvement. CYP2E1 inhibition reduced circulating 19-HETE levels and alleviated myocardial injury. Integrative transcriptomic and experimental analyses further identified fibroblast growth factor 21 (FGF21) as an upstream regulator associated with CYP2E1-related oxidative metabolism. FGF21 deficiency aggravated CYP2E1-associated metabolic remodeling after MI, whereas FGF21 restoration suppressed CYP2E1 expression and 19-HETE accumulation through activation of sirtuin 1 (Sirt1). Moreover, we found that Sacubitril/Valsartan attenuated CYP2E1-associated metabolic remodeling in an FGF21-dependent manner. These findings support CYP2E1-associated lipid metabolic remodeling as a contributor to oxidative injury during MI and suggest a potential therapeutic relevance of targeting this pathway.
Vo Nam Xuan NX, Pham Huong Lai HL, Bui Tan Trong TT, Bui Tien Thuy TT
Objectives: Dyslipidemia is a major driver of cardiovascular disease (CVD), causing a global economic burden. Statins are the mainstay for reducing LDL-C, with pitavastatin (PIT) being the newest-generation statin, showing non-inferior efficacy compared with potent statins. This study aims to assess the cost-effectiveness of pitavastatin in comparison with atorvastatin (ATOR) and rosuvastatin (ROS). Method: The PubMed, Cochrane, and Embase databases were searched to identify full or partial economic evaluations through 19 November 2025. Our primary outcome is the incremental cost-effectiveness ratio (ICER), with health outcomes measured by quality-adjusted life years (QALYs) or percentage reduction in LDL-C. Regarding quality assessment, the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 tool was applied. The Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) checklist and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) were performed for RCTs and non-RCT risk assessments, respectively. Result: Five studies were synthesized. One model-based analysis over a lifetime revealed that PIT was less expensive but generated slightly fewer QALYs than ATOR and was dominated by ROS. Four within-trial CEAs with follow-up ≤12 months found that for each 1% reduction in LDL-C, PIT was generally more economical than low-dose ATOR but consistently more costly than ROS. Conclusions: Because of the small number and heterogeneity of studies, it is not possible to draw firm conclusions about the cost-effectiveness of PIT. Further model-based analyses with an adequate sample size and comprehensive costing are needed to clarify the economic role of PIT.
DiStefano Jill J, Pierson Natalie W NW
Sacubitril/valsartan is a foundational component of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF), demonstrating reductions in cardiovascular mortality and hospitalization in PARADIGM-HF. The introduction of generic sacubitril/valsartan was expected to improve affordability and expand access. However, real-world experience suggests that financial and administrative barriers persist despite generic availability. High deductibles under Medicare Part D, variable formulary placement, loss of manufacturer copay assistance, prior authorization requirements, and digital enrollment barriers continue to disrupt therapy continuity. These obstacles disproportionately affect elderly and socioeconomically vulnerable patients and contribute to cost-related nonadherence, treatment interruption and 'financial toxicity': the negative effects of the economic burden of medical care on patients. From a frontline clinical perspective, financial toxicity functions as a modifiable risk factor in HFrEF management. Aligning benefit design with evidence-based care is necessary to ensure that generic availability translates into sustained access and clinical benefit.
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