Search Results (129)

Background: Fixed-dose combinations of rosuvastatin and ezetimibe are increasingly used in clinical practice, but real-world data on their effectiveness and safety in large populations remain limited. Methods: This prospective, single-group, open-label, non-interventional observational study was conducted in the Republic of Korea to evaluate the effectiveness and safety of Rovazet^® (a fixed-dose combination of rosuvastatin and ezetimibe). Patients were prospectively enrolled from 235 institutions (50 general hospitals and 185 private clinics) as part of routine clinical practice over a five-year period. Lipid profiles and medication compliance questionnaire results were collected at baseline, 12 weeks, and 24 weeks of treatment. Results: A total of 5527 patients with dyslipidemia, the majority were men (53.0%), and the mean age was 60.4 years. Rovazet^® significantly reduced low-density lipoprotein cholesterol (LDL-C) by 23.5% at 12 weeks (from 117.47 ± 50.65 mg/dL to 81.14 ± 38.20 mg/dL; p < 0.0001) and by 27.4% at 24 weeks (from 117.47 ± 50.65 mg/dL to 74.52 ± 33.36 mg/dL; p < 0.0001). Total cholesterol was significantly reduced by 17.7% at 12 weeks and by 19.8% at 24 weeks. Rovazet^® treatment reduced triglycerides by 4.1% at 12 weeks and by 7.2% at 24 weeks. High-density lipoprotein cholesterol increased by 4.5% at 12 weeks and by 7.9% at 24 weeks following Rovazet^® treatment. These changes in lipid profiles were consistent, regardless of cardiovascular risk profiles. By 24 weeks of treatment with Rovazet^®, 91.8% of patients had reached their target LDL-C goals. Adverse drug reactions were reported in 2.81% of patients, most of which were minor, indicating that Rovazet^® was well tolerated. Conclusions: Rovazet^® was effective in improving lipid profiles and well tolerated in Korean adults with dyslipidemia. Full article

Objectives: The goal of this study was to investigate lipid goal achievement rates in very high-risk patients over six months using high-intensity rosuvastatin or rosuvastatin/ezetimibe combination lipid-lowering therapy. Methods: This prospective, observational study was conducted on the patients of 150 general and 60 specialist practices. Our analysis included 3017 patients (47% women) who completed six months of therapy. Of these, 55.5% had pre-existing cardiovascular disease, 35.6% had cerebrovascular disease, and 20.4% had peripheral vascular disease. Results: At six months, in patients receiving rosuvastatin monotherapy (20.5%), the 1.8 LDL-C achievement rate was 37%; in those taking the fix rosuvastatin/ezetimibe combination (63.7%), it was 52%, and the 1.4 level attainment proved to be 11% and 22%, respectively. The rates of LDL-C reduction of at least 50% were 32% and 42%, respectively. Overall, non-HDL-C goal achievement rates were higher than when LDL-C was calculated using the Martin–Hopkins or Sampson methods but similar to those calculated with the Friedewald formula. When patients were stratified by triglyceride quartiles, non-HDL-C goal achievement rates were significantly higher (p < 0.001) in cases with triglyceride levels below 1.2 mmol/L. Conversely, Friedewald-calculated LDL-C (F-LDL-C) goal achievement rates were significantly higher (p < 0.001) in patients with triglyceride levels above 1.7 mmol/L. Conclusions: Our findings suggest that the consistent use of fixed high-intensity statin and ezetimibe combinations can improve lipid goal achievement. However, comparing the achievement of LDL-C goals (calculated by three methods) and non-HDL-C goals also confirmed that the common practice of automatically adding 0.8 mmol/L to the calculated LDL-C value to determine non-HDL-C leads to inaccuracies, particularly in the lower triglyceride ranges. Full article

Background/Objectives: Hepatic clearance is important in determining clinical drug administration strategies. Achieving accurate hepatic clearance predictions through in vitro-to-in vivo extrapolation (IVIVE) relies on appropriate model selection, which is a critical step. Although numerous models have been developed to estimate drug dosage, some may fail to predict liver drug clearance owing to inappropriate hepatic clearance models during IVIVE. To address this limitation, an in silico-based model selection approach for optimizing hepatic clearance predictions was introduced in a previous study. The current study extends this strategy by verifying the accuracy of the selected models using ex situ experimental data, particularly for drugs whose model choices are influenced by protein binding. Methods: Commonly prescribed drugs were classified according to their hepatic extraction ratios and protein-binding properties. Building on previous studies that employed multinomial logistic regression analysis for model selection, a three-phase classification method was implemented to identify five representative drugs: diazepam, diclofenac, rosuvastatin, fluoxetine, and tolbutamide. Subsequently, an isolated perfused rat liver (IPRL) system was used to evaluate the accuracy of the in silico method. Results: As the unbound fraction increased for diazepam and diclofenac, the most suitable predictive model shifted from the initially preferred well-stirred model (WSM) to the modified well-stirred model (MWSM). For rosuvastatin, the MWSM provided a more accurate prediction. These three capacity-limited, binding-sensitive drugs conformed to the outcomes predicted by the multinomial logistic regression analysis. Fluoxetine was best described by the WSM, which is consistent with its flow-limited classification. For tolbutamide, a representative capacity-limited, binding-insensitive drug, no significant differences were observed among the various models. Conclusions: These findings demonstrate the accuracy of an in silico-based model selection approach for predicting liver metabolism and highlight its potential for guiding dosage adjustments. Furthermore, the IPRL system serves as a practical tool for validating the accuracy of the results derived from this approach. Full article

Background: Lipid metabolism disturbances are common in end-stage renal disease (ESRD) patients on hemodialysis (HD), leading to dyslipidemia, which is characterized by abnormal plasma lipids and lipoproteins. Although large randomized controlled trials have generally not demonstrated a survival benefit associated with statin therapy among patients receiving hemodialysis, limited observational studies have reported potential associations with improved clinical outcomes in this population. Methods: This retrospective cohort study investigated the clinical and safety outcomes of statin use in ESRD patients on HD with documented dyslipidemia over a two-year period from 1 January 2018 to 30 December 2019. The primary endpoints evaluated the clinical outcomes of statins by assessing changes in specific lipid parameters, including low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). The secondary endpoints assessed safety by monitoring liver enzymes and creatine kinase (CK) levels. Results: Among 179 participants, diabetes mellitus was present in 134 patients (74.9%), while 168 patients (93.9%) had hypertension. Cardiovascular events occurred in 95 patients (53.1%). Statin therapy was administered to 146 patients (82.0%), with atorvastatin being the most frequently prescribed statin (69.3%). Modest reductions in LDL-C levels were observed in the rosuvastatin and atorvastatin groups, whereas slight increases were noted in the simvastatin and non-statin groups. None of these within-group changes were statistically significant. In the atorvastatin group, LDL-C decreased slightly from 2.058 to 2.003 mmol/L. The rosuvastatin group experienced a more pronounced LDL-C reduction from 2.607 to 2.113 mmol/L. Conversely, the simvastatin group showed an LDL-C increase from 1.550 to 1.901 mmol/L. Among the non-statin group, LDL-C increased from 2.678 to 2.820 mmol/L. Liver enzyme and CK levels fluctuated slightly but remained within normal ranges. Conclusions: This study evaluated statin therapy in hemodialysis patients with dyslipidemia. Although modest reductions in LDL-C levels were observed in the atorvastatin and rosuvastatin groups, statin therapy did not reduce the incidence of atherosclerotic events in hemodialysis patients with dyslipidemia. Additionally, statin use was not associated with any clinically or statistically significant effects. Full article

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population. Full article

Introduction: There are no clear predictors of high-sensitivity C-reactive protein (hsCRP) reductions following the use of antihypertensives and statins. Also, there are no clear data on the effect of BMI on hsCRP changes following the use of antihypertensives and statins. Therefore, we sought to identify predictors of significant hsCRP reduction after the use of rosuvastatin (RSV)/amlodipine (AML) and atorvastatin (ATV)/AML. Methods: We included 237 patients from 21 institutions in the Republic of Korea. Patients were randomly assigned to one of three treatment groups: RSV 10 mg/AML 5 mg; RSV 20 mg/AML 5 mg; or ATV 20 mg/AML 5 mg. Multivariate logistic regression analysis was performed to evaluate the predictors for hsCRP responders (hsCRP reduction ≥ 40% after 8 weeks). We also compared baseline hsCRP levels and their changes after 8 weeks between obese patients (n = 153) and nonobese patients (n = 84). Results: Baseline hsCRP ≥ 2 mg/dL and RSV 20 mg/AML 5 mg were independent predictors of hsCRP responders. Their median hsCRP % change rates were −53.11% and −40.0%, respectively. Normal weight, pre-obesity, and obesity were not independent predictors of hsCRP responders. The median hsCRP % reduction rates among normal weight, pre-obese, and obese patients were less than 40% in all groups, and the differences between each group were not significant (−20.0% vs. −33.33 vs. −23.08%, p = 0.289). Conclusions: In patients with ATV, RSV/AML polypill, baseline hsCRP ≥ 2 mg/dL, and baseline RSV 20 mg/AML 5 mg were independent predictors of a significant hsCRP reduction. BMI was not associated with hsCRP reduction (Clinical trial: NCT03951207). Full article

Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan^® examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH. Full article

Background: Fatty liver disease and obesity are among the most prevalent health conditions in modern society and have recently garnered significant attention. Semaglutide, a well-known anti-obesity drug, has been widely used for diabetes and obesity treatment; however, nanotherapeutics utilizing semaglutide have not yet been developed. Methods: A novel statin–lipid conjugate was synthesized using rosuvastatin and ursodeoxycholic acid, a liver-protective agent. This conjugate was then formulated with semaglutide through hydrophobic interactions to create a new nanoparticle system. The physicochemical properties of the nanoparticles were analyzed, and their therapeutic efficacy was evaluated in a high-fat diet (HFD)-induced animal model. Results: The statin–lipid conjugate was successfully synthesized, forming novel nanoparticles with semaglutide in an aqueous solution. These nanoparticles exhibited distinct properties compared to conventional semaglutide formulations. In animal experiments, the treatment group demonstrated a 30.24% reduction in body weight and a 46.80% improvement in liver function markers compared to the control group. Conclusions: This study introduces a novel semaglutide-based nanoparticle (SRLC NP) system that overcomes key limitations of conventional semaglutide therapy by providing enhanced bioavailability, extended circulation time, and improved cellular uptake. These findings highlight the potential of SRLC NPs as a clinically translatable nanotherapeutic approach for more effective, sustained, and patient-friendly obesity and fatty liver disease treatment. Full article

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a transformative approach for cancer treatment, demonstrating remarkable success in patients with relapsed and refractory hematological malignancies. However, challenges persist in optimizing CAR-T cell production and improving therapeutic outcomes. One of the major hurdles is the efficiency of retroviral or lentiviral transduction during CAR-T cell manufacturing. Additionally, the heterogeneity of T-cell populations isolated from patients can impact CAR-T cell effectiveness and persistence in vivo. This article explores a novel strategy to address these challenges by focusing on serum-free medium and additive optimization. We propose a unique approach that incorporates the culturing of T cells in Nutri-T medium, along with 24 h of exposure to combined low concentrations of BX795 and rosuvastatin, to enhance the transduction efficacy and functionality of CAR-T cells. The results presented here provide promising insights into the potential of this strategy to produce more effective CAR-T cells for immunotherapy, ultimately advancing the field and benefiting cancer patients worldwide. Full article

Background/Objectives: The increasing use of statins in people with cystic fibrosis (CF) necessitates the investigation of potential drug–drug interactions (DDI) of statins with cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor, tezacaftor, and ivacaftor (ETI). The interactions may involve the potential inhibition of cytochrome P450 isoenzymes (CYPs), organic anion-transporting polypeptides (OATPs), and Breast Cancer Resistance Protein (BCRP) by ETI. This presents a therapeutic challenge in CF due to the potential for elevated statin levels, consequently heightening the risk of myopathy. This study aimed to predict potential DDIs between statins and ETI using a physiologically based pharmacokinetic (PBPK) modeling approach. Methods: We performed in vitro assays to measure the inhibitory potency of ETI against OATPs and CYP2C9 and incorporated these data into our PBPK models alongside published inhibitory parameters for BCRP and CYP3A4. Results: The PBPK simulation showed that atorvastatin had the highest predicted AUC ratio (3.27), followed by pravastatin (2.27), pitavastatin (2.24), and rosuvastatin (1.83). Conclusions: Based on these findings, rosuvastatin appears to exhibit a weak interaction with ETI, whereas other statins exhibited a moderate interaction, potentially requiring appropriate dose reductions. These data indicate potential clinically significant DDIs between ETI and certain statins, which warrants a clinical study to validate these findings. Full article

Background/Objectives: It has been shown that the use of statins in patients with type 2 diabetes mellitus (T2DM) worsens hyperglycemia and hemoglobin A1c levels but may help in the preservation of pancreatic β-cell function. The potential role of a high pancreatic fat fraction (PFF) in this process has not yet been clarified. This study aimed to investigate whether the liver fat fraction (LFF) and PFF in T2DM patients is affected by statin therapy. Methods: This cross-sectional study involved a total of 140 T2DM patients, including both those who were receiving (n = 70) and those who were not receiving (n = 70) statin therapy. The mapping of the LFF and PFF utilizing the IDEAL-IQ sequence was conducted in magnetic resonance imaging. Results: In T2DM patients who used statins, the median PFF was higher compared to those who did not use statins (8.4 vs. 6.2%, p = 0.021), while the median LFF was found to be similar (8.4 vs. 8.9, p = 0.572). Variations in PFF were associated with the use of various statins (non-statin group: 6.2 vs. atovastatin: 8.7 vs. rosuvastatin: 3.2 vs. pitavastatin: 9.2, p = 0.004). The multivariable regression analysis indicated that insulin usage decreased log(LFF) by a factor of 0.16-fold (ꞵ ± SE = −0.16 ± 0.05, p = 0.010), and rosuvastatin usage reduced log(PFF) by 0.16-fold (ꞵ ± SE = −0.16 ± 0.07, p = 0.025), irrespective of other risk factors. Furthermore, the use of atorvastatin (ꞵ ± SE = 0.17 ± 0.06, p = 0.011) and pitavastatin (ꞵ ± SE = 0.19 ± 0.07, p = 0.008) were independently associated with an increase in log(PFF). Conclusions: In patients with T2DM, statin use did not show a significant effect on the liver fat fraction, but it caused differences in the pancreatic fat fraction. The observation of a lower pancreatic fat fraction in patients taking a rosuvastatin and atorvastatin dose of 40 mg/day suggests that different types and doses of statins may have varying effects on pancreatic fat accumulation. Full article

Background/Objectives: The gold standard in the non-surgical treatment of periodontitis is scaling and root planning (SRP). In recent years, studies have emerged suggesting additional clinical benefits from the use of statins as an adjunct to classical periodontal disease treatment. The aim of the present study was to review the relevant literature relating to the subgingival use of statins as an adjunctive treatment to the classical, non-surgical treatment of periodontitis, with a particular focus on groups with general factors that may affect the outcome of treatment. Methods: The authors conducted a systematic review following the PRISMA 2020 guidelines. The electronic literature search conducted included the MEDLINE (PubMed) database, Web of Science, Scopus, and Google Scholar from 1 January 2012 to 14 June 2024. The keywords used for the PubMed search were determined with the help of the MeSH Browser Tool and were as follows: Periodontitis [Mesh] AND Statin [Mesh] OR Simvastatin [Mesh] OR Atorvastatin [Mesh] or Rosuvastatin Calcium [Mesh]. Based on the authors’ inclusion and exclusion criteria, 20 results were included in the review, out of 937. Results: The improvement was more pronounced in patients without systematic diseases compared to those with type II diabetes and in non-smokers compared to smoking patients. Greater improvements in clinical and radiological parameters were seen in patients diagnosed with aggressive periodontitis compared to patients with chronic periodontitis. Conclusions: This literature review led the authors to the conclusion that statins applied locally might be competent agents for improving the therapeutic outcomes of SRP. Full article

Liver cancer is a prevalent form of carcinoma worldwide. A novel chitosan-coated optimized formulation capped with irradiated silver nanoparticles (INops) was fabricated to boost the anti-malignant impact of rosuvastatin calcium (RC). Using a 2³-factorial design, eight formulations were produced using the solvent evaporation process. The formulations were characterized in vitro to identify the optimal formulation (Nop). The FTIR spectra showed that the fingerprint region is not superimposed with that of the drug; DSC thermal analysis depicted a negligible peak shift; and XRPD diffractograms revealed the disappearance of the typical drug peaks. Nop had an entrapment efficiency percent (EE%) of 86.2%, a polydispersity index (PDI) of 0.254, a zeta potential (ZP) of −35.3 mV, and a drug release after 12 h (Q12) of 55.6%. The chitosan-coated optimized formulation (CS.Nop) showed significant mucoadhesive strength that was 1.7-fold greater than Nop. Physical stability analysis of CS.Nop revealed negligible alterations in VS, ZP, PDI, and drug retention (DR) at 4 °C. The irradiated chitosan-coated optimized formulation capped with silver nanoparticles (INops) revealed the highest inhibition effect on carcinoma cells (97.12%) compared to the chitosan-coated optimized formulation (CS.Nop; 81.64) and chitosan-coated optimized formulation capped with silver nanoparticles (CS.Nop.AgNPs; 92.41). The bioavailability of CS-Nop was 4.95-fold greater than RC, with a residence time of about twice the free drug. CS.Nop has displayed a strong in vitro–in vivo correlation with R² 0.9887. The authors could propose that novel INop could serve as an advanced platform to improve oral bioavailability and enhance hepatic carcinoma recovery. Full article

Introduction: This study assessed the therapeutic effectiveness of a single-pill combination (SPC) of olmesartan/amlodipine plus rosuvastatin for blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with hypertension and dyslipidemia. Methods: Adult patients with hypertension and dyslipidemia who were decided to be treated with the study drug were eligible. The primary endpoint was the proportion of patients who achieved BP, LDL-C and both BP and LDL-C treatment goals at weeks 24–48. Secondary endpoints were assessed at weeks 24–48 and included changes in BP and LDL-C levels from baseline; the proportion of patients who achieved treatment goals who were initially classified as uncontrolled at baseline; changes and percent changes in lipid parameters; changes in both BP and LDL-C levels among patients who reached treatment goals who were followed for more than 24 weeks; and the overall safety profile. Results: A total of 5476 patients were enrolled, and 4411 patients comprised the effectiveness evaluation set. The proportions of patients who reached the treatment goals for BP, LDL-C levels, and both BP and LDL-C levels were 67.93% [95% confidence interval (CI) 66.52–69.32], 80.19% [95% CI 78.85–81.49], and 58.07% [95% CI 56.43–59.7], respectively. Secondary endpoints showed statistically significant changes. Overall, the treatment was well tolerated. Conclusions: The treatment of patients with hypertension and dyslipidemia with the olmesartan/amlodipine plus rosuvastatin SPC was associated with significant decreases in SBP/DBP and LDL-C levels, and a high proportion of patients achieved the BP and LDL-C treatment goals. The finding of this study is worthwhile in that this study evaluated the effectiveness and safety in a broad patient population representative of those seen in everyday clinical practice. Full article

Objectives: Dyslipidemia, a significant risk factor for cardiovascular disease (CVD), is marked by abnormal lipid levels, such as the elevated lowering of low-density lipoprotein cholesterol (LDL-C). Statins are the first-line treatment for LDL-C reduction. Pitavastatin (PIT) has shown potential in lowering LDL-C and improving high-density lipoprotein cholesterol (HDL-C). This review assesses pitavastatin’s efficacy, effectiveness, and safety in dyslipidemia management in Asia. Methods: A systematic review was conducted using PubMed, Cochrane, and Embase databases up to November 2024, adhering to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies (12 RCTs and 5 non-RCTs) were analyzed, focusing on LDL-C reduction, safety profiles, and adverse events. The quality of the studies was assessed using checklists to ensure the selection of the best studies and to limit bias. Results: Pitavastatin doses (1–4 mg) reduced LDL-C by 28–47%, comparable to atorvastatin, rosuvastatin, and simvastatin. The 2 mg dose matched atorvastatin’s 10 mg dose in efficacy for both short-term (35–42%) and long-term (28–36%) use. LDL-C target achievement rates were 75–95%. Adverse events, including mild myalgia and elevated liver enzymes, were rare, and discontinuation rates were low. Conclusions: Pitavastatin is an effective and safe alternative to traditional statins for dyslipidemia management in Asia. Further research on long-term outcomes and high-risk groups is warranted. Full article