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Revista Medica Del Instituto Mexicano... Mar 2023Dyslipidemia is a risk factor for the development of atherosclerosis and ischemic heart disease. Statins are safe drugs that are part of the routine treatment in...
BACKGROUND
Dyslipidemia is a risk factor for the development of atherosclerosis and ischemic heart disease. Statins are safe drugs that are part of the routine treatment in patients with Acute Myocardial Infarction (AMI), however, rhabdomyolysis associated with severe myonecrosis due to statins can occur and associated complications such as acute kidney injury increase mortality. The main objective of this article is to report the case of a critically ill patient with AMI who presented severe statin-associated rhabdomyolysis documented with muscle biopsy.
DESCRIPTION OF THE CASE
A 54-year-old man who presented with AMI, cardiogenic shock, and cardiorespiratory arrest requiring cardiopulmonary resuscitation, fibrinolysis, and successful salvage coronary angiography. However, he presented severe rhabdomyolysis associated with atorvastatin that required suspension of the drug and multi-organ support in a Coronary Care Unit.
CONCLUSIONS
The prevalence of statin-associated rhabdomyolysis is low, however, the late elevation of CPK above 10 times its upper normal value in those patients with successful percutaneous coronary angiography should promptly draw attention, generate a diagnostic approach towards non-traumatic acquired causes of rhabdomyolysis and assess the suspension of statins.
Topics: Male; Humans; Middle Aged; Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Risk Factors; Rhabdomyolysis
PubMed: 37207311
DOI: No ID Found -
Journal of the American College of... May 2020
Topics: Atorvastatin; Cholesterol, LDL; Humans; Risk Factors
PubMed: 32209335
DOI: 10.1016/j.jacc.2020.03.033 -
Experimental Biology and Medicine... Dec 2021High levels of blood glucose and lipids are well-known risk factors for heart diseases. Bee venom is a natural product that has a potent hypoglycemic, hypolipidemic,...
High levels of blood glucose and lipids are well-known risk factors for heart diseases. Bee venom is a natural product that has a potent hypoglycemic, hypolipidemic, anti-inflammatory, and antioxidant effects. The current study aimed to determine the bee venom effects on cardiac dysfunction compared to combined therapy of metformin and atorvastatin in diabetic hyperlipidemic rats. The median lethal dose of bee venom was estimated, and then 50 adult male albino rats were categorized into five groups. One group was fed a standard diet and served as a negative control, while the other groups were given nicotinamide and streptozotocin injections to induce type 2 diabetes. After confirming diabetes, the rats were fed a high-fat diet for four weeks. The four groups were divided as follows: one group served as a positive control, whereas the other three groups were treated with bee venom (0.5 mg/kg), bee venom (1.23 mg/kg), and combined therapy of metformin (60 mg/kg) and atorvastatin (10 mg/kg), respectively, for four weeks. Upon termination of the experiment, blood samples and heart tissue were obtained. Administration of bee venom using both doses (0.5 and 1.23 mg/kg) and combined therapy of metformin and atorvastatin revealed a significant decrease in the concentrations of glucose, total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, troponin I, creatine kinase, and lactate dehydrogenase activities. Moreover, a significant decrease had been detedcted in malondialdehyde, nuclear factor-kappa-β levels, and relative mRNA expression of vascular cell adhesion molecule-1 and galectin-3 in heart tissue compared to the positive control ( < 0.0001). Furthermore, there was a significant increase in bodyweight levels of insulin, high-density lipoprotein cholesterol, and total antioxidant capacity in heart tissue compared to the positive control ( < 0.0001). The results indicate that bee venom can ameliorate cardiac dysfunction through attenuating oxidative stress and downregulating the NF-κβ signaling pathway.
Topics: Animals; Atorvastatin; Bee Venoms; Diabetes Mellitus, Experimental; Diet, High-Fat; Heart; Hyperlipidemias; Male; Metformin; Rats
PubMed: 34550826
DOI: 10.1177/15353702211045924 -
Drug Design, Development and Therapy 2018Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Major cardiovascular risk factors, including hypertension and dyslipidemia, are often comorbidities, frequently leading to concurrent prescription of angiotensin receptor blockers and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). The study's objective was to evaluate the effect of coadministration of fimasartan and atorvastatin on their pharmacokinetics (PKs).
SUBJECTS AND METHODS
In a randomized, open-label, three-period, six-sequence, crossover, multiple-dose study, 36 healthy subjects received 120 mg fimasartan, 40 mg atorvastatin, or both (based on their assigned sequence) once daily for 7 days in each period, with a 7-day washout between periods. Blood samples for the PK analysis of fimasartan, atorvastatin, and the 2-hydroxy atorvastatin metabolite were collected up to 48 h after the last dose.
RESULTS
The coadministration of fimasartan and atorvastatin was well tolerated and led to an increase in the peak concentration and area under the concentration-time curve at steady state of fimasartan by 2.18-fold (95% confidence interval [CI], 1.79-2.65) and 1.35-fold (95% CI, 1.26-1.43) and those of atorvastatin increased by 1.82-fold (95% CI, 1.51-2.18) and 1.12-fold (95% CI, 1.04-1.22), respectively.
CONCLUSION
Coadministration increased the systemic exposures of fimasartan and atorvastatin, but the clinical significance of this finding needs to be evaluated with respect to exposure responses and clinical outcomes.
Topics: Administration, Oral; Adult; Atorvastatin; Biphenyl Compounds; Cross-Over Studies; Drug Combinations; Healthy Volunteers; Humans; Male; Middle Aged; Pyrimidines; Tetrazoles; Young Adult
PubMed: 30087555
DOI: 10.2147/DDDT.S165171 -
European Journal of Pharmaceutical... Jun 2021We investigated the effects of mineral oil on statin pharmacokinetics and inflammatory markers in animal models. A new synthesis strategy produced regioisomers that...
We investigated the effects of mineral oil on statin pharmacokinetics and inflammatory markers in animal models. A new synthesis strategy produced regioisomers that facilitated the characterization of the main metabolite (M1) of atorvastatin, a lipophilic statin, in C57BL/6NCrl mice. The chemical structure of M1 in mice was confirmed as ortho-hydroxy β-oxidized atorvastatin. Atorvastatin and M1 pharmacokinetics and inflammatory markers were assessed in C57BL6/J mice given atorvastatin 5 mg/kg/day or 10 mg/kg/day, as a single dose or for 21 days, with or without 10 µL or 30 µL mineral oil. No consistent differences in plasma exposure of atorvastatin or M1 were observed in mice after single or repeat dosing of atorvastatin with or without mineral oil. However, mice administered atorvastatin 10 mg/kg with 30 µL mineral oil for 21 days had significantly increased plasma levels of serum amyloid A (mean 9.6 µg/mL vs 7.9 µg/mL without mineral oil; p < 0.01) and significantly increased proportions of C62L B cells (mean 18% vs 12% without mineral oil; p = 0.04). There were no statistically significant differences for other inflammatory markers assessed. In dogs, pharmacokinetics of atorvastatin, its two hydroxy metabolites and pravastatin (a hydrophilic statin) were evaluated after single administration of atorvastatin 10 mg plus pravastatin 40 mg with or without 2 g mineral oil. Pharmacokinetics of atorvastatin, hydroxylated atorvastatin metabolites or pravastatin were not significantly different after single dosing with or without mineral oil in dogs. Collectively, the results in mice and dogs indicate that mineral oil does not affect atorvastatin or pravastatin pharmacokinetics, but could cause low-grade inflammation with chronic oral administration, which warrants further investigation.
Topics: Animals; Atorvastatin; Dogs; Heptanoic Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mice; Mice, Inbred C57BL; Mineral Oil; Pravastatin; Pyrroles
PubMed: 33667667
DOI: 10.1016/j.ejps.2021.105776 -
American Journal of Physiology.... Mar 2023The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However,...
The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia () were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver ( < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content ( < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue ( < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish ( < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.
Topics: Animals; Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins; Cholesterol; Liver; Triglycerides; Lipoproteins, VLDL; Adipose Tissue; Lipid Metabolism; Mammals
PubMed: 36572553
DOI: 10.1152/ajpregu.00222.2022 -
Diabetes, Obesity & Metabolism Dec 2019The PLANET trials showed that atorvastatin 80 mg but not rosuvastatin at either 10 or 40 mg reduced urinary protein to creatinine ratio (UPCR) at similar effects on... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
The PLANET trials showed that atorvastatin 80 mg but not rosuvastatin at either 10 or 40 mg reduced urinary protein to creatinine ratio (UPCR) at similar effects on LDL-cholesterol. However, individual changes in both UPCR and LDL-cholesterol during treatment with these statins varied widely between patients. This inter-individual variability could not be explained by patients' physical or biochemical characteristics. We assessed whether the plasma concentrations of both statins were associated with LDL-cholesterol and UPCR response.
MATERIALS AND METHODS
The PLANET trials randomized patients with a UPCR of 500-5000 mg/g and fasting LDL-cholesterol >2.33 mmol/L to a 52-week treatment with atorvastatin 80 mg, rosuvastatin 10 mg or 40 mg. For the current analysis, patients with available samples at week 52 and treatment compliance >80% by pill count were included (N = 295). The main outcome measurements were percentage change in UPCR and absolute change in LDL-cholesterol (delta LDL) from baseline to week 52.
RESULTS
Median (interquartile range) plasma concentration at week 52 for atorvastatin 80 mg was 3.9 ng/mL (IQR: 2.1 to 8.7), for rosuvastatin 10 mg 1.0 ng/mL (IQR: 0.7 to 2.0) and for rosuvastatin 40 mg 3.5 ng/mL (IQR: 2.0 to 6.8). Higher plasma concentration of statin was associated with larger LDL-cholesterol reductions at week 52 [rosuvastatin r = -0.40 (P < .001); atorvastatin r = -0.28 (P = .006)]. The plasma concentration of both statins did not correlate with UPCR change [rosuvastatin r = 0.07 (P = .30); atorvastatin r = 0.16 (P = .13)].
CONCLUSIONS
Individual variation in plasma concentrations of rosuvastatin and atorvastatin was associated with LDL-cholesterol changes in patients. The individual variation in UPCR change was not associated with the plasma concentration of both statins.
Topics: Adult; Aged; Anticholesteremic Agents; Atorvastatin; Cholesterol, LDL; Creatinine; Diabetes Complications; Female; Humans; Kidney Function Tests; Male; Middle Aged; Proteinuria; Renal Insufficiency, Chronic; Rosuvastatin Calcium
PubMed: 31414562
DOI: 10.1111/dom.13849 -
Investigative and Clinical Urology May 2022Our purpose was to verify the effects of atorvastatin (ATO) on prostate cancer (PCa) proliferation, apoptosis, invasion, and metastasis and to further explore the drug's...
PURPOSE
Our purpose was to verify the effects of atorvastatin (ATO) on prostate cancer (PCa) proliferation, apoptosis, invasion, and metastasis and to further explore the drug's mechanism of action.
MATERIALS AND METHODS
We used cell counting kit-8 (CCK8) and clone formation experiments to study the effect of ATO on the proliferation of PC3 cells. Flow cytometry and Hoechst 33342 staining were used to detect cell apoptosis. Cell migration and invasion were detected through wound healing experiments and transwell experiments. Western blotting was applied to detect apoptosis-related proteins (BAX, Bcl-2, PARP, and Caspase-3), epithelial-mesenchymal transformation (EMT) proteins, and matrix metalloproteinase (MMP) expression. A mouse xenograft tumor model was established, and tumor volume and weight were determined. The expression levels of the above-mentioned proteins were determined through western blot.
RESULTS
ATO inhibited PC-3 cell proliferation and promoted cell apoptosis in a dose-dependent manner. ATO significantly up-regulated the expression of BAX, PARP, and Caspase-3 and inhibited the expression of Bcl-2. Wound healing and transwell experiments showed that ATO inhibited invasion and metastasis in PC-3 cells, possibly because ATO could inhibit the EMT and the expression of MMPs in PC-3 cells. Studies in nude mice showed that ATO significantly reduced tumor volume and weight; the expression levels of related proteins were consistent with the results.
CONCLUSIONS
ATO inhibits the occurrence and development of PCa and regulates the migration and invasion of PCa cells by inhibiting the EMT and MMPs.
Topics: Animals; Atorvastatin; Caspase 3; Cell Line, Tumor; Cell Proliferation; Epithelial-Mesenchymal Transition; Humans; Male; Matrix Metalloproteinases; Mice; Mice, Nude; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; bcl-2-Associated X Protein
PubMed: 35534220
DOI: 10.4111/icu.20210411 -
International Wound Journal Dec 2023This study aimed to develop atorvastatin-loaded emulgel and nano-emulgel dosage forms and investigate their efficiency on surgical wound healing and reducing... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of topical atorvastatin-loaded emulgel and nano-emulgel 1% on post-laparotomy pain and wound healing: A randomized double-blind placebo-controlled clinical trial.
This study aimed to develop atorvastatin-loaded emulgel and nano-emulgel dosage forms and investigate their efficiency on surgical wound healing and reducing post-operative pain. This double-blind randomized clinical trial was conducted in a surgical ward of a tertiary care hospital affiliated with university of medical sciences. The eligible patients were adults aged 18 years or older who were undergoing laparotomy. The participants were randomized in a 1:1:1 ratio to one of three following groups of atorvastatin-loaded emulgel 1% (n = 20), atorvastatin-loaded nano-emulgel 1% (n = 20), and placebo emulgel (n = 20) twice a day for 14 days. The primary outcome was the Redness, Edema, Ecchymosis, Discharge, and Approximation (REEDA) scores to determine the rate of wound healing. The Visual Analogue Scale (VAS) and quality of life were the secondary outcomes of this study. A total of 241 patients assessed for eligibility; of them, 60 patients completed the study and considered for final evaluation. A significant decrease in REEDA score was observed on Days 7 (63%) and 14 (93%) of treatment with atorvastatin nano-emulgel (p-value < 0.001). A significant decrease of 57% and 89% in REEDA score was reported at Days 7 and 14, respectively, in atorvastatin the emulgel group (p-value < 0.001). Reduction in pain VAS in the atorvastatin nano-emulgel was also recorded at Days 7 and 14 of the intervention. The results of the present study suggested that both topical atorvastatin-loaded emulgel and nano-emulgel 1% were effective in acceleration of wound healing and alleviation of pain of laparotomy surgical wounds, without causing intolerable side effects.
Topics: Adult; Humans; Atorvastatin; Double-Blind Method; Laparotomy; Pain, Postoperative; Quality of Life; Wound Healing
PubMed: 37382345
DOI: 10.1111/iwj.14289 -
Journal of Clinical Hypertension... Oct 2020Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed-dose combination (FDC) versus...
Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed-dose combination (FDC) versus free-equivalent combination (FEC) of amlodipine and atorvastatin in the treatment of concurrent hypertension and dyslipidemia remain unknown. In this study, we included patients with newly diagnosed hypertension and dyslipidemia, without previously established cardiovascular disease, and treated with either FDC or FEC of amlodipine and atorvastatin were identified from the National Health Insurance Research Database of Taiwan and follow-up for 5 years. By using 1:1 propensity score matching, a total of 1756 patients were enrolled in this study. The composite of major adverse cardiovascular events, including all-cause mortality, myocardial infarction (MI), stroke, and coronary revascularization, occurred more frequently in the FEC group than in the FDC group (hazard ratio, 1.88; 95% confidence interval [CI], 1.42 to 2.5). Although the all-cause mortality did not differ (hazard ratio, 0.46; 95% CI, 0.36 to 1.59), the FEC group developed increased MI, stroke, and coronary revascularization (hazard ratio, 2.87; 95% CI, 1.07 to 7.68; hazard ratio, 1.97; 95% CI, 1.41 to 2.74; and hazard ratio, 2.44; 95% CI, 1.26 to 4.69, respectively). Furthermore, as an unexpected result, a higher risk to develop new-onset diabetes mellitus was observed with FEC regimens (hazard ratio, 2.19; 95% CI, 1.6 to 3.0). In conclusion, although the all-cause mortality did not differ between the two groups, the FDC regimen of amlodipine and atorvastatin improved clinical outcomes when compared to FEC in patients with newly diagnosed hypertension and dyslipidemia.
Topics: Amlodipine; Antihypertensive Agents; Atorvastatin; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Humans; Hypertension; Mortality; Taiwan; Treatment Outcome
PubMed: 32862551
DOI: 10.1111/jch.14016