Statin Group Research Articles

Determining the role of statins in Parkinson's disease risk reduction and disease modification: A comprehensive meta-analysis of 4 million participants' data.

Many observational studies have examined the association between statins and the incidence of Parkinson's disease (PD) in high-risk populations. On the other hand, clinical trials as well as other observational studies investigated the safety and efficacy of statins in slowing disease progression in PD patients. However, the evidence has been inconclusive in both questions. To that end, we conducted this systematic review and meta-analysis to synthesize evidence on the role of statins in decreasing the risk of PD among high-risk populations and as a possible disease-modifying agent for patients with PD. A comprehensive literature search of electronic databases including PubMed, Scopus, Cochrane, and Web of Science has been performed. Relevant studies were chosen and data were extracted and analyzed using RevMan software version 5.4.1. Twenty-five studies (14 cohort, 9 case-control, and 2 randomized controlled trials) have been included in the present systematic review. Of them, 21 studies reported the association between statins and PD risk. Statins were found to significantly reduce the risk of developing PD (pooled RR 0.86, 95% CI [0.77-0.95], p < 0.005). Four studies investigated statins as a disease-modifying agent. The pooled mean difference (MD) in the UPDRS-III from baseline to endpoint did not differ significantly between the statin and control groups (MD -1.34 points, 95% CI [-3.81 to 1.14], p = 0.29). Although epidemiological observational studies showed that statin use was associated with a reduced risk of PD, current evidence is insufficient to support the role of statins in slowing the progression of PD. These findings are limited by the fact that most of the included studies are observational studies which carry a high risk of confounding bias which highlights the need for future well-designed RCTs.

Intensive Versus Moderate Statin-Based Therapies in Patients With Mild Ischemic Stroke: A Prospective Multicenter Cohort Study.

Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16mg/dl in the treat-to-target strategy group and 64 ± 18mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. ClinicalTrials.gov, NCT02579499.

Pharmacophore Modeling and Binding Affinity of Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase.

Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba's compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = -8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = -7.84 kcal/mol; Ki = 7.96µM). From ashitaba's compounds, it was found that 4'-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxychalcone have low ΔG of below -6 kcal/mol. The lowest ΔG value was found in 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxy chalcone with a ΔG of -6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = -5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = -6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity.

Statins for neuroprotection in spontaneous intracerebral haemorrhage (STATIC): protocol for a multicentre, prospective and randomised controlled trial

IntroductionIntracerebral haemorrhage (ICH) is a neurological emergency with high morbidity and mortality, and current treatment is limited. Emerging evidence has reported that statins can exert neuroprotective effects in cerebrovascular diseases....

Cholesterol Gallstones and Long-Term Use of Statins: Is Gut Microbiota Dysbiosis Bridging over Uncertainties?

A total of 300 research participants-200 consecutive patients diagnosed with dyslipidemia (100 statin (+), treated for at least five years, and 100 statin (-)) and 100 healthy controls-were included in this observational study. The aim of the study was to deliver insights into the relationship between the long-term use of statins for dyslipidemia and gallstone disease (GSD), as well as insights into the background particularities of the gut microbiota. All study participants underwent clinical examination, laboratory workups, stool microbiology/stool 16S r RNA, next-generation sequencing, and abdominal ultrasound/CT exams. Results: The research participants presented with similarities related to age, gender, and location. Patients displayed comparable heredity for GSs, metabolic issues, and related co-morbidities. Gut dysbiosis (DB) was present in 54% of the statin (-) patients vs. 35% of the statin (+) patients (p = 0.0070). GSs were present in 14% of patients in the statin (-) group vs. 5% of patients in the statin (+) group (p = 0.0304). Severe dysbiosis, with a significant reduction in biodiversity, an increase in LPS (+) bacteria, and a notable decrease in mucin-degrading bacteria, mucosa-protective bacteria, and butyrate-producing bacteria were observed in the statin (-) group. Strong positive correlations between GSD and diabetes/impaired glucose tolerance (r = 0.3368, p = 0.0006), obesity (r = 0.3923, p < 0.0001), nonalcoholic fatty liver disease (r = 0.3219, p = 0.0011), and DB (r = 0.7343, p < 0.0001), as well as significant negative correlations between GSD and alcohol use (r = -0.2305, p = 0.0211), were observed. The multiple regression equation demonstrated that only DB (95% CI: 0.3163 to 0.5670; p < 0.0001) and obesity (95% CI: 0.01431 to 0.2578; p = 0.0289) were independent risk factors predicting GSD in the group of patients treated with statins. Conclusion: The long-term use of statins in dyslipidemic patients was associated with a low risk of developing GSs. The gut microbiota associated with a long-term use of statins in dyslipidemic patients was characterized by a low risk of developing an imbalance of various functional bacteria and alterations in the metabolic microbiota. DB and obesity were found to be independent risk factors predicting GSD in statin (+) patients.

Association between circulatory microRNA-218 expression, serum PCSK9 levels, inflammatory markers, and monocyte subsets in coronary artery disease patients: impact of statin therapy

BackgroundProprotein convertase subtilisin/kexin type-9 (PCSK9), an enzyme produced mainly by hepatocytes and breaks low-density lipoprotein receptor (LDL-R), inflammatory markers [toll like receptor 4 (TLR4), high mobility group box 1 (HMGB1), tumor necrosis factor alpha (TNFα), c-reactive protein (CRP)], and monocyte subtypes are associated with coronary artery disease (CAD) pathogenesis. The circulating microRNA-218 (miR-218) can relieve CAD through the suppression of HMGB1 in monocyte-derived inflammatory cytokines. Herein, we explored the association between circulatory miR-218 expression and serum levels of PCSK9, inflammatory markers, and monocyte subtypes in statin and non-statin CAD patients. This study involved 91 healthy (control) and 91 stable CAD participants which were subdivided into no-statin (NS, n = 25), low-statin (LS, n = 25), and high-statin (HS, n = 41) groups. low-density lipoprotein cholesterol (LDL-C) and CRP serum levels were calorimetrically determined. Serum levels of PCSK9, TLR4, HMGB1, and TNFα were detected by ELISA, while monocyte subsets [classical (CM), intermediate (IM), non-classical (NC)] were calculated by flow cytometry. Circulatory miR-218 expression was detected by real-time PCR.ResultsThe CAD group had significantly lower miR-218 expression and significantly higher levels of PCSK9, inflammatory markers (HMGB1, CRP, TLR4, and TNFα), and IM% than the control group. Among CAD patients, LS and HS groups had significantly lower miR-218 expression, LDL-C levels, and inflammatory markers and significantly higher levels of PCSK9 than the NS group. The HS group exhibited the lowest miR-218 expression and inflammatory markers and the highest PCSK9 levels. However, there were no significant changes in IM% among statin and non-statin groups. In the three CAD groups, miR-218 showed a significantly negative correlation with PCSK9 and inflammatory markers (HMGB1, CRP, TLR4, and TNFα), while this expression exhibited a significantly negative correlation with CM%, IM%, and NCM% only in the NS group. Results of multivariable linear regression indicated a correlation between miR-218 and five independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα) in the total statin (LS + HS) group, and eight independent variables (PCSK9, HMGB1, CRP, TLR4, and TNFα, CM%, IM%, NCM%) in the NS group. Provided that all other independent variables are constant, miR-218 expression was significantly correlated to CRP (Beta = 0.234) and PCSK9 (Beta = − 0.875) in the total statin group; TLR4 (Beta = − 0.554) in the LS group; HMGB1 (Beta = − 0.507) in the HS group; and CRP (Beta = − 0.745) in the NS group.ConclusionsStatin-treated CAD patients have a unique negative correlation between miR-218 and PCSK9, HMGB1, and TLR4, and subsequently with CAD progress. Therefore, it could be recommended to combine activators of miR-218 and inhibitors of PCSK9, HMGB1, and TLR4 with statin to efficiently treat CAD.

Association between statin therapy and long-term clinical outcomes in patients with stable coronary disease undergoing percutaneous coronary intervention

This longitudinal cohort study examined the long-term effect of statin therapy on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). A total of 1760 patients with stable coronary artery disease (CAD) were divided by receipt of statin therapy or not after index PCI. Baseline clinical characteristics, risk factors, angiographic findings, and medications after interventional procedure were assessed to compare long-term clinical outcomes between groups. Predictors for all-cause death and major adverse cardiovascular events (MACE), including myocardial infarction (MI), cardiovascular death, and repeated PCI procedures, were also analyzed. The statin therapy group had higher average serum cholesterol and more elevated low-density lipoprotein cholesterol (LDL-C) than the non-statin therapy group (189.0 ± 47.9 vs 169.3 ± 37.00 mg/dl, 117.2 ± 42.6 vs 98.7 ± 31.8 mg/dl, respectively, both P < 0.001). The non-statin group had higher rates of all-cause death and cardiovascular death compared to statin group (both P < 0.001). After adjustment for age, diabetes, and chronic kidney disease, Cox proportion hazard analysis revealed statin use significantly reduced all-cause death and repeated PCI procedure (hazard ratio: 0.53 and 0.69, respectively). Statin use seemed not reduce the hazard of cardiovascular death or MI in patients with stable CAD after PCI; however, statin therapy still was associated with reduced rates of all-cause death and repeat PCI procedure.

Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and In vitro - In vivo Correlation.

Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube. The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A in vitro-in vivo correlation (IVIVC) for Ros SNEDDS. An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. In vitro dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS. The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin Cmax in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the in vitro dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y2 as it presented the lowest values of AIC. Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.

Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia

Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. ClinicalTrials.gov Identifier: NCT03635749.

INFLUENCE OF STATINS ON ARTERIAL STIFFNESS AND BLOOD PRESSURE CONTROL IN PATIENTS WITH SEVERE ARTERIAL HYPERTENSION

Objective: In some studies, there was well established a statin influence on arterial stiffness. It was suggested statins could decrease the blood pressure too. Pulse wave velocity (PWV), a gold standard for arterial stiffness measurement, depends on blood pressure (BP). The aim of study was to evaluate the influence of statins on PWV changes in dependency on normalization of the 24-h BP. Design and method: In study, there were included 46 patients (mean age 55.6 ±1.07, f/male 47.8/52.2%) with systolic (SBP)/diastolic (DBP) BP &gt;/=180/110 mmHg, who were treated in specialized unit. Baseline and at the 6th month of combination therapy (mean medicines - 3.8±1.2), we provided office/ambulatory BP and PWV measurements. Results: At 6th month, only 39.1% had 24-h BP &lt;130/80. PWV changes under treatment are present in tab. In statin treatment group we noted significant PWV lowering in spite of BP control. In patients without statins, PWV decreased significantly only in subgroup with achieved the target 24-h BP. In statin group 66.7% achieved target 24-h BP compared to 33.3% in statin (-) group (p=0.048). Conclusions: The statin therapy is able to improve the arterial stiffness (independently to BP control) and helps to achieve the target BP.

Association between pre-treatment with statin and its inhibitory effect on the onset of coronary artery disease at the time of coronary computed tomography angiography: a new look at an old medication.

Coronary artery stenosis is often advanced by the time coronary computed tomography angiography (CCTA). Statins are the most important anti-lipidemic medication for improving the prognosis of coronary artery disease (CAD) patients. Although lipid-lowering therapy using statins appears to have been established as a method for preventing CAD, there remains the problem that CAD cannot be completely suppressed. In this study, we investigated whether pre-treatment with statin could significantly inhibit the onset of CAD when patients received CCTA for screening of CAD. The subjects were 1164 patients who underwent CCTA as screening for CAD. CAD was diagnosed when 50% or more coronary stenosis was present in the coronary arteries. Patient backgrounds were investigated by age, gender, body mass index, coronary risk factors [family history of cardiovascular diseases, smoking history, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, chronic kidney disease (CKD) or metabolic sydrome] and medications. Patients were classified into two groups according to the presence or absence of statin pre-administration during CCTA [statin (-) group (n = 804) and (+) group (n = 360)]. Compared with the statin (-) group, the statin (+) group was significantly older and had higher rates of family history, HTN, and DM. The statin (+) group had a significantly higher % CAD than the statin (-) group. Serum levels of low-density lipoprotein cholesterol (LDL-C) were significantly lower in the statin (+) group than in the statin (-) group. There was no significant difference in either high-density lipoprotein cholesterol levels or triglyceride levels between the two groups. Age, male gender, HTN, DM and pre-treatment with statin were all associated with CAD (+) in all patients. In addition, factors that contributed to CAD (+) in the statin (-) group were age, male gender, and DM, and factors that contributed to CAD (+) in the statin (+) group were age, smoking, HTN and % maximum dose of statin. At the time of CCTA, the statin (+) group had a high rate of CAD and coronary artery stenosis progressed despite a reduction of LDL-C levels. To prevent the onset of CAD, in addition to strict control of other coronary risk factors (HTN etc.), further LDL cholesterol-lowering therapy may be necessary.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats.

Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process. A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay. Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group. In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Determination of Pharmacokinetic and Toxicological Parameters of Some Commonly Used Statin Group Drugs

Statins work as inhibitors of the HMG-CoA reductase enzyme and are the most commonly prescribed cholesterol-lowering drug group for people with cardiovascular disease or risk. This study aimed to determine the pharmacokinetic parameters and toxicities of conventional and new-generation cholesterol drugs such as atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin and pitavastatin. Absorption, distribution, metabolism, and excretion (ADME) parameters and toxicity predictions of drugs were made using in silico modeling, which gives faster results than animal experiments and does not involve any laboratory costs. In calculations made using structural similarity, compounds' pharmacokinetic properties and toxicity predictions are obtained based on previously known structure-activity data. The study results showed that the toxicity classifications of the drugs were 5 (LD: 5000 mg/kg) for atorvastatin and 6 (LD: 8939 mg/kg) for pravastatin, respectively. The toxicity classes were found to be 4 for all the other statin group drugs. The results showed that pravastatin had the lowest toxicity among investigated cholesterol drugs, while pitavastatin and fluvastatin had the highest toxic effects. Accordingly, it is recommended that the consequences of using pravastatin and atorvastatin, cholesterol drugs with lower toxicity classes, should be investigated more seriously in terms of minimum toxic substance intake for patient groups requiring high doses of medication.

Effects of Administration and Intensity of Statins on Mortality in Patients Undergoing Hemodialysis.

(1) Background: Few studies have investigated the association between the intensity of statins and patient survival rates in patients undergoing hemodialysis (HD) as primary outcomes. This study aimed to evaluate patient survival rates according to the intensity of statins using a large sample of patients undergoing maintenance HD. (2) Methods: Data from a national HD quality assessment program were used in this study (n = 53,345). We divided the patients into four groups based on the administration and intensity of statins: Group 1, patients without a prescription of statins (n = 37,944); Group 2, patients with a prescription of a low intensity of statins (n = 700); Group 3, patients with a prescription of a moderate intensity of statins (n = 14,160); Group 4, patients with a prescription of a high intensity of statins (n = 541). (3) Results: Significant differences in baseline characteristics were observed among the four groups. Group 1 had the best patient survival among the four groups in the univariate Cox regression analyses. However, multivariable Cox regression analyses showed that the patient survival rate was higher for Group 3 than for Group 1. Cox regression analyses using data of a balanced cohort showed that, on univariate analyses, the HRs were 0.93 (95% CI, 0.91-0.95, p < 0.001) in Group 2 and 0.95 (95% CI, 0.93-0.96, p < 0.001) in Group 3 compared to that in Group 1. Group 4 had a higher mortality rate than Groups 2 or 3. The results from the cohort after balancing showed a similar trend to those from the multivariable Cox regression analyses. Young age and less comorbidities in Group 1 were mainly associated with favorable survival in Group 1 in the univariate analysis using cohort before balancing. Among the subgroup analyses based on sex, age, presence of diabetes mellitus, and heart disease, most multivariable analyses showed significantly higher patient survival rates in Group 3 than for Group 1. (4) Conclusions: Our study exhibited significant differences in baseline characteristics between the groups, leading to limitations in establishing a robust association between statin intensity and clinical outcomes. However, we conducted various statistical analyses to mitigate these differences. Some results, including multivariable analyses controlling for baseline characteristics and analyses of a balanced cohort using propensity score weighting, indicated improved patient survival in the moderate-intensity statin group compared to non-users. These findings suggest that moderate statin use may be associated with favorable patient survival.

Patterns of Statin Therapy Use and Associated Outcomes in Older Veterans Across Kidney Function

BackgroundDespite significant morbidity and mortality related to atherosclerotic cardiovascular disease, to date, most major clinical trials studying the effects of statin therapy have excluded older adults. The objective of this analysis was to evaluate the effect of initiating statin therapy on incident dementia and mortality among individuals 75 years of age or older across the complete spectrum of kidney function. MethodsWe conducted a retrospective cohort study of 640,191 VA health system patients who turned 75 years of age between 2000 and 2018. Patients on statin therapy received the medication for an average of 6.3 years (standard deviation 4.6 years). The primary outcome of interest included incident dementia diagnosis during the study period. The secondary outcome was all-cause mortality. Cox proportional hazard analysis was used to evaluate the adjusted association of statin initiation with these outcomes. ResultsThere was a higher rate of incident dementia in the No Statin group (4.7%) vs the Statin group (3.2%). Additionally, we observed a 22% all-cause mortality benefit associated with statin therapy. We did not observe a treatment effect with respect to primary or secondary outcomes across varying levels of kidney function. ConclusionThis large cohort study did not reveal an association between the initiation of statin therapy and incident dementia. A survival benefit was seen in statin users compared with nonusers. Prospective studies in more diverse populations including older adults will be needed to verify these findings.

Effect of statins on severity of coronary artery lesion and clinical prognosis in patients with coronary heart disease

To investigate the effect of statins on the severity of coronary artery lesion in patients with coronary heart disease, and to analyze the risk factors of clinical prognosis. A retrospective cohort study was conducted. The clinical data of 156 patients with coronary heart disease and completed the second re-examination of coronary CT angiography (CCTA) who were admitted to the department of cardiovascular medicine of Peking University People's Hospital from January 2017 to December 2021 were collected. According to whether they took statins regularly according to the doctor's instructions after being diagnosed with coronary heart disease based on the first CCTA examination, the patients were divided into statin group and non-statin group, and the clinical characteristics of the two groups and the results of the second re-examination of CCTA were compared and analyzed. According to whether the patients had major adverse cardiovascular and cerebrovascular events (MACCE) within 3-5 years after diagnosis of coronary heart disease, the patients were divided into MACCE group and non-MACCE group, and the clinical characteristics of the two groups were compared and analyzed. Multivariate Logistic regression analysis was used to screen the risk factors related to the adverse prognosis (occurrence of MACCE) of patients with coronary heart disease. (1) A total of 156 patients with coronary heart disease were enrolled, including 113 patients (72.44%) in the statin group and 43 patients (27.56%) in the non-statin group. Except for low density lipoprotein (LDL) and serum creatinine (SCr), there was no significant difference in gender, age, body mass index (BMI), basic diseases, smoking history, the first CCTA display of coronary artery lesions and plaque characteristics, the interval between the two CCTA and other laboratory indicators between the two groups. Compared with the non-statin group, the statin group had a significant reduction in the overall increase rate of coronary artery stenosis score (Gensini score) in the CCTA re-examination and the incidence of MACCE [Gensini score increase rate: 25.66% (29/113) vs. 46.51% (20/43), incidence of MACCE: 9.73% (11/113) vs. 30.23% (13/43), both P < 0.05]. (2) Among 156 patients with coronary heart disease, 24 cases (15.38%) experienced MACCE within 3-5 years after diagnosis, while 132 cases (84.62%) did not experience MACCE. The proportion of patients in the MACCE group who regularly took statins after diagnosis was significantly lower than that in the non-MACCE group [45.83% (11/24) vs. 77.27% (102/132), P < 0.01], and D-dimer and glycosylated hemoglobin (HbA1c) were significantly higher than those in the non-MACCE group [D-dimer (μg/L): 148.50 (101.25, 314.75) vs. 88.10 (59.03, 132.12), HbA1c: 6.45% (6.20%, 7.93%) vs. 6.10% (5.81%, 6.92%), both P < 0.05]. Compared with the non-MACCE group, in the first CCTA examination of patients in the MACCE group, the total percentage of atheroma volume (PAV), fibrous-fat PAV, necrotic core PAV and Gensini score were significantly increased [total PAV: 43.05% (29.19%, 60.60%) vs. 24.57% (16.94%, 39.09%), fibrous-fat PAV: 18.61% (8.48%, 26.44%) vs. 6.81% (4.16%, 12.57%), necrotic core PAV: 5.96% (2.98%, 8.71%) vs. 2.29% (1.47%, 4.36%), Gensini score: 30.25 (23.50, 38.30) vs. 19.50 (13.20, 31.10), all P < 0.05]. Multivariate Logistic regression analysis showed that regular use of statins [odds ratio (OR) = 0.282, 95% confidence interval (95%CI) was 0.110-0.727, P = 0.008], D-dimer (OR = 1.011, 95%CI was 1.005-1.017, P < 0.001), necrotic core PAV (OR = 1.323, 95%CI was 1.120-1.563, P = 0.001) and Gensini score (OR = 1.038, 95%CI was 1.004-1.073, P = 0.028) were independent risk factors for MACCE within 3-5 years after diagnosis in patients with coronary heart disease. For patients with coronary heart disease, D-dimer, necrotic core PAV, and Gensini scores should be closely monitored. Statins can effectively alleviate the severity of coronary artery disease and reduce the occurrence of MACCE in patients with coronary artery disease.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults

BackgroundStatins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). ObjectiveInvestigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. MethodsWe included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and ‘moderate or high’ intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. ResultsCompared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17–1.95); p<0.01], stroke [HR 1.47 (1.14–1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19–1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. ConclusionLack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis.

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.

A retrospective study on the effect of statins on mortality and antimicrobial resistance among patients with Staphylococcus aureus bloodstream infection.

There is insufficient evidence in statin on the treatment of Staphylococcus aureus (SA) infection, we observe and analyze the clinical outcomes and antibiotic resistance of SA bloodstream infections in patients who received statins. A retrospective study was carried out in SA bloodstream infection of hospitalized patients from January 2018 to August 2023. The 30-day attributable mortality, 30-day all-cause mortality and clinical data of patients who received statins and non-statins were compared. A total of 74 patients with SA bloodstream infection were included, 32 (43.2%) patients received treatment with statins and 42 (56.8%) with non-statins. The incidence of methicillin-resistant SA (MRSA) was significantly lower in the statins group (15.6% vs. 38.1%, p = 0.034), however, no significant differences were observed in the mortality rate (p = 0.410). This study revealed the superiority of statins in reducing incidence of MRSA among SA bloodstream infection patients, but statins do not improve the 30-day mortality rate.