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PloS One 2021Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, open-label, parallel, multi-center Phase IV study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high-risk Asian patients with hypercholesterolemia.
BACKGROUND
Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia.
METHODS
A 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint.
RESULTS
LDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk patients) with atorvastatin 20 mg than with 10 mg (40.3% vs. 25.6%, p < 0.05). Apolipoprotein B decreased significantly with atorvastatin 20mg versus 10 mg (-36.2% vs. -29.9%, p < 0.05). Lipid ratios also showed greater improvement with atorvastatin 20 mg than with 10 mg (total cholesterol/high-density lipoprotein cholesterol ratio, -33.3% vs. -29.4%, p < 0.05; apolipoprotein B/apolipoprotein A1 ratio, -36.7% vs. -31.4%, p < 0.05). Atorvastatin 20 mg was more cost-effective than atorvastatin 10 mg in terms of both the average and incremental cost-effectiveness ratios. Safety and tolerability of atorvastatin 20 mg were comparable to those of atorvastatin 10 mg.
CONCLUSION
In high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg.
Topics: Anticholesteremic Agents; Asian People; Atorvastatin; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Prognosis; Republic of Korea
PubMed: 33481866
DOI: 10.1371/journal.pone.0245481 -
European Journal of Clinical... Mar 2022Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD)... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults.
METHODS
This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models.
RESULTS
Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00).
CONCLUSION
There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.
Topics: Aged; Aged, 80 and over; Atorvastatin; Cardiovascular Diseases; Disabled Persons; Double-Blind Method; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Pravastatin; Primary Prevention; Proportional Hazards Models; Rosuvastatin Calcium; Simvastatin
PubMed: 34698889
DOI: 10.1007/s00228-021-03239-1 -
Chirurgia (Bucharest, Romania : 1990) 2020Ischeamia reperfusion injury is a frequent challenge during tissue reconstruction. Atorvastatin and Sildenafil, have been studied for their protective and/or... (Comparative Study)
Comparative Study
Ischeamia reperfusion injury is a frequent challenge during tissue reconstruction. Atorvastatin and Sildenafil, have been studied for their protective and/or therapeutic effects on various organ systems subjected to IRI. The aim of the present study was to compare a single dose of Atorvastatin and Sildenafil pretreatment on acute oxidative/nitrosative stress and the subsequent dermal flap necrosis. Forty-five Sprague-Dawley rats, were randomly allocated into three equal groups(n=15): Group A: Control rats treated with intraperitoneal saline, Group B: Sildenafil group, and Group C: atorvastatin group. All rats underwent flap elevation and inferior epigastric artery occlusion thirty minutes after drug administration. Myeloperoxidase activity, malondialdehyde levels and inducible nitric oxide synthase activity were evaluated 12 hours after reperfusion. Flap survivability was analysed 7 days after the procedure. Statistically significant reduction was detected in sildenafil and atorvastation. Measurements of myelopyroxidase followed a similar pattern, interestingly malonadehyde levels measured to be significantly lower in the sildenafil group. Contrary, iNOS activity atorvastatin was significantly elevated in atorvastatin group. Conclusion: The single dose of atorvastatin or sildenafil increase flap survivability almost equally, however only atorvastatin enhances significantly iNOS expression.
Topics: Animals; Atorvastatin; Disease Models, Animal; Graft Survival; Necrosis; Nitric Oxide; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sildenafil Citrate; Skin; Surgical Flaps; Treatment Outcome; Vasodilator Agents
PubMed: 33378637
DOI: 10.21614/chirurgia.115.6.783 -
Medical Science Monitor : International... Jun 2018BACKGROUND At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. Meanwhile, hyperhomocysteinemia...
BACKGROUND At present, a constant progress in pathophysiology understanding and treatment of the chronic heart failure (CHF) is arising. Meanwhile, hyperhomocysteinemia (HHcy) has been linked to impaired left ventricular function and clinical class in patients with CHF. Atorvastatin therapy can reduce the incidence of sudden cardiac death in patients with advanced CHF. Folic acid could enhance endothelial function in vascular disease states. The present study aims to investigate the effect of atorvastatin and folic acid combined on the cardiac function and ventricular remodeling in CHF patients with HHcy. MATERIAL AND METHODS Elderly CHF patients with HHcy were divided into four groups: routine, routine + atorvastatin, routine + folic acid, and routine + atorvastatin + folic acid groups. Serum homocysteine (Hcy) level was detected using enzymatic cycling methods, and N-terminal pro brain natriuretic peptide (NT-proBNP) level by ELISA. The cardiac function indexes and left ventricular early diastolic peak flow velocity/atrial systolic peak flow velocity (E/A) ratio were evaluated. The six-minute walk test was performed to measure the six-minute walk distance (6MWD). RESULTS 6MWD increased, the serum Hcy and NT-proBNP levels decreased, and cardiac function was improved compared with before treatment, which was the most significant in the routine + atorvastatin + folic acid group, followed by the routine + atorvastatin group, then the routine + folic acid group, and lastly, the routine group. CONCLUSIONS The results indicated that the combination of atorvastatin and folic acid improved the cardiac function and inhibited ventricular remodeling of elderly CHF patients with HHcy.
Topics: Aged; Aged, 80 and over; Atorvastatin; China; Chronic Disease; Female; Folic Acid; Heart Failure; Heart Function Tests; Humans; Hyperhomocysteinemia; Male; Middle Aged; Ventricular Remodeling
PubMed: 29863106
DOI: 10.12659/MSM.906893 -
Medicine Jun 2021Globally, coronary heart disease (CHD) is a primary cause of morbidity leading to disabilities and mortality. Modern clinical practice adopts several pharmacological...
BACKGROUND
Globally, coronary heart disease (CHD) is a primary cause of morbidity leading to disabilities and mortality. Modern clinical practice adopts several pharmacological methods to treat CHD. Angina pectoris refers to sever chest pain due to CHD, it has a profound impact on the wellbeing of patients. Moreover, angina pectoris is a crucial prognosis predictor. The aim of the current study is to evaluate the effectiveness and safeness of using combined rosuvastatin and atorvastatin to treat CHD patients.
METHODS
A systematic literature search for articles will be conducted on several electronic databases from their inception to May 2021. The search will include all randomized controlled trials examining the use of rosuvastatin in combination with atorvastatin to treat CHD patients. The databases are as follows: MEDLINE, Web of Science, the Cochrane Library, WanFang database, China National Knowledge Infrastructure, and EMBASE. A couple of authors will independently assess the eligibility, extract study data, and assess the possibility of bias. Moreover, depending on the type of data and heterogeneity of the included studies, either the Mantel-Haensel fixed-effect model or the DerSimonian-Laird random-effect model will be used to estimate the relative risk, mean differences, or standardized mean differences and 95% confidence intervals. All differences in opinion shall be decided by involving an additional author in the discussion. Lastly, the RevMan software (version: 5.3) will be used to perform sensitivity analysis, data synthesis, and risk of bias assessment.
RESULTS
The effectiveness and security of using rosuvastatin in combination with atorvastatin to treat CHD patients will be systematically evaluated.
CONCLUSION
This study will provide evidence to evaluate the efficacy and security of using a combination of rosuvastatin and atorvastatin to treat CHD patients.
ETHICS AND DISSEMINATION
Ethical approval will not be required since it is based on already published data.
REGISTRATION NUMBER
DOI 10.17605/OSF.IO/VYBDR (https://osf.io/vybdr/).
Topics: Anticholesteremic Agents; Atorvastatin; Coronary Disease; Drug Therapy, Combination; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Research Design; Rosuvastatin Calcium; Systematic Reviews as Topic; Treatment Outcome
PubMed: 34128881
DOI: 10.1097/MD.0000000000026340 -
Advanced Science (Weinheim,... Mar 2024Exploration of medicines for efficient and safe management of metabolic-associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective...
Hepatic-Accumulated Obeticholic Acid and Atorvastatin Self-Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic-Associated Fatty Liver Disease.
Exploration of medicines for efficient and safe management of metabolic-associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic-targeted nanodrugs composed of OCA and cholesterol-lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier-free nanocrystals (OCAHTs) are self-assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter-mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen-challenged mice and high-fat diet-induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD-associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter-based strategy for hepatic-targeting drug delivery but also presents an efficient and safe full-API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.
Topics: Animals; Mice; Atorvastatin; Non-alcoholic Fatty Liver Disease; Inflammation; Chenodeoxycholic Acid
PubMed: 38196299
DOI: 10.1002/advs.202308866 -
International Journal of Molecular... Apr 2018Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of...
Radiation of the chest during cancer therapy is deleterious to the heart, mostly due to oxidative stress and inflammation related injury. A single sub-lethal dose of irradiation has been shown to result in compensatory up-regulation of the myocardial connexin-43 (Cx43), activation of the protein kinase C (PKC) signaling along with the decline of microRNA (miR)-1 and an increase of miR-21 levels in the left ventricle (LV). We investigated whether drugs with antioxidant, anti-inflammatory or vasodilating properties, such as aspirin, atorvastatin, and sildenafil, may affect myocardial response in the LV and right ventricle (RV) following chest irradiation. Adult, male Wistar rats were subjected to a single sub-lethal dose of chest radiation at 25 Gy and treated with aspirin (3 mg/day), atorvastatin (0.25 mg/day), and sildenafil (0.3 mg/day) for six weeks. Cx43, PKCε and PKCδ proteins expression and levels of miR-1 as well as miR-21 were determined in the LV and RV. Results showed that the suppression of miR-1 was associated with an increase of total and phosphorylated forms of Cx43 as well as PKCε expression in the LV while having no effect in the RV post-irradiation as compared to the non-irradiated rats. Treatment with aspirin and atorvastatin prevented an increase in the expression of Cx43 and PKCε without change in the miR-1 levels. Furthermore, treatment with aspirin, atorvastatin, and sildenafil completely prevented an increase of miR-21 in the LV while having partial effect in the RV post irradiation. The increase in pro-apoptotic PKCδ was not affected by any of the used treatment. In conclusion, irradiation and drug-induced changes were less pronounced in the RV as compared to the LV. Treatment with aspirin and atorvastatin interfered with irradiation-induced compensatory changes in myocardial Cx43 protein and miR-21 by preventing their elevation, possibly via amelioration of oxidative stress and inflammation.
Topics: Animals; Antioxidants; Aspirin; Atorvastatin; Connexin 43; Heart; Male; MicroRNAs; Myocardium; Radiation Injuries; Radiation, Ionizing; Rats; Rats, Wistar
PubMed: 29642568
DOI: 10.3390/ijms19041128 -
The Pediatric Infectious Disease Journal Jan 2017Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for...
BACKGROUND
Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population.
METHODS
HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy.
RESULTS
Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin.
CONCLUSIONS
Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children.
Topics: Adolescent; Adult; Anti-HIV Agents; Atorvastatin; C-Reactive Protein; Child; Female; HIV Infections; Humans; Hyperlipidemias; Male; Young Adult
PubMed: 27749649
DOI: 10.1097/INF.0000000000001352 -
Acta Biochimica Et Biophysica Sinica Apr 2021In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption...
In clinic, perioperative neurocognitive disorder is becoming a common complication of surgery in old patients. Neuroinflammation and blood-brain barrier (BBB) disruption are important contributors for cognitive impairment. Atorvastatin, as a strong HMG-CoA reductase inhibitor, has been widely used in clinic. However, it remains unclear whether atorvastatin could prevent anesthesia and surgery-induced BBB disruption and cognitive injury by its anti-inflammatory property. In this study, aged C57BL/6J mice were used to address this question. Initially, the mice were subject to atorvastatin treatment for 7 days (10 mg/kg). After a simple laparotomy under 1.5% isoflurane anesthesia, Morris water maze was performed to assess spatial learning and memory. Western blot analysis, immunohistochemistry, and enzyme-linked immunosorbent assay were used to examine the inflammatory response, BBB integrity, and cell apoptosis. Terminal-deoxynucleotidyl transferase mediated nick end labeling assay was used to assess cell apoptosis. The fluorescein sodium and transmission electron microscopy were used to detect the permeability and structure of BBB. The results showed that anesthesia and surgery significantly injured hippocampal-dependent learning and memory, which was ameliorated by atorvastatin. Atorvastatin could also reverse the surgery-induced increase of systemic and hippocampal cytokines, including IL-1β, TNF-α, and IL-6, accompanied by inhibiting the nuclear factor kappa-B (NF-κB) pathway and Nucleotide-Binding Oligomerization Domain, or Leucine Rich Repeat and Pyrin Domain Containing 3 (NLRP3) inflammasome activation, as well as hippocampal neuronal apoptosis. In addition, surgery triggered an increase of BBB permeability, paralleled by a decrease of the ZO-1, occludin, and Claudin 5 proteins in the hippocampus. However, atorvastatin treatment could protect the BBB integrity from the impact of surgery, by up-regulating the expressions of ZO-1, occludin, and Claudin 5. These findings suggest that atorvastatin exhibits neuroprotective effects on cognition in aged mice undergoing surgery.
Topics: Aging; Animals; Atorvastatin; Blood-Brain Barrier; Cognitive Dysfunction; Inflammasomes; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Surgical Procedures, Operative
PubMed: 33674828
DOI: 10.1093/abbs/gmab022 -
Acta Pharmaceutica (Zagreb, Croatia) Sep 2011In the present work, three different spectrophotometric methods for simultaneous estimation of ramipril, aspirin and atorvastatin calcium in raw materials and in...
In the present work, three different spectrophotometric methods for simultaneous estimation of ramipril, aspirin and atorvastatin calcium in raw materials and in formulations are described. Overlapped data was quantitatively resolved by using chemometric methods, viz. inverse least squares (ILS), principal component regression (PCR) and partial least squares (PLS). Calibrations were constructed using the absorption data matrix corresponding to the concentration data matrix. The linearity range was found to be 1-5, 10-50 and 2-10 μg mL-1 for ramipril, aspirin and atorvastatin calcium, respectively. The absorbance matrix was obtained by measuring the zero-order absorbance in the wavelength range between 210 and 320 nm. A training set design of the concentration data corresponding to the ramipril, aspirin and atorvastatin calcium mixtures was organized statistically to maximize the information content from the spectra and to minimize the error of multivariate calibrations. By applying the respective algorithms for PLS 1, PCR and ILS to the measured spectra of the calibration set, a suitable model was obtained. This model was selected on the basis of RMSECV and RMSEP values. The same was applied to the prediction set and capsule formulation. Mean recoveries of the commercial formulation set together with the figures of merit (calibration sensitivity, selectivity, limit of detection, limit of quantification and analytical sensitivity) were estimated. Validity of the proposed approaches was successfully assessed for analyses of drugs in the various prepared physical mixtures and formulations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticholesteremic Agents; Antihypertensive Agents; Aspirin; Atorvastatin; Calibration; Capsules; Chemistry, Pharmaceutical; Heptanoic Acids; Humans; Least-Squares Analysis; Models, Theoretical; Pyrroles; Ramipril; Regression Analysis; Reproducibility of Results; Spectrophotometry, Ultraviolet
PubMed: 21945907
DOI: 10.2478/v10007-011-0027-1