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Current Opinion in Infectious Diseases Feb 2016To evaluate evidence that statins reduce cardiovascular risk in patients living with HIV. (Review)
Review
PURPOSE OF REVIEW
To evaluate evidence that statins reduce cardiovascular risk in patients living with HIV.
RECENT FINDINGS
Moderate to high-dose atorvastatin and rosuvastatin appear to reduce noncalcified coronary plaque volume and slow progression of carotid intima-media thickness in patients with treated HIV infection. Expected lipoprotein changes with statins on the background of modern antiretroviral therapy are similar to the general population. In addition to lipids, the statin benefit may be mediated in part by improvements in vascular inflammation and levels of T-cell and monocyte activation. One concern is the potential for rosuvastatin to cause insulin resistance. Decisions to prescribe statins must be done in the context of global risk assessment, but traditional risk calculators such as the Framingham Risk Score or the American College of Cardiology/American Heart Association pooled-risk equations underestimate risk in this population. Furthermore, many patients with subclinical disease would not be recommended for statins according to the most recent American College of Cardiology/American Heart Association guidelines.
SUMMARY
Statins are likely to improve cardiovascular outcomes for patients with HIV, but results of the first outcome study are not expected until 2020. In the meantime, clinicians should individualize statin prescriptions, and should consider using more potent statins (rosuvastatin, atorvastatin, and pitavastatin) when possible.
Topics: Atorvastatin; Carotid Intima-Media Thickness; Coronary Disease; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin Resistance; Practice Guidelines as Topic; Practice Patterns, Physicians'; Precision Medicine; Primary Prevention; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Treatment Outcome; United States
PubMed: 26658651
DOI: 10.1097/QCO.0000000000000223 -
Pharmacogenomics Dec 2018
Topics: Africa; Black People; Hepatocytes; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Rosuvastatin Calcium
PubMed: 30398065
DOI: 10.2217/pgs-2018-0168 -
European Journal of Clinical... Mar 2023We investigated the efficacy of intensive rosuvastatin therapy plus 7-day dual antiplatelet therapy (DAPT) in reducing stroke recurrence for patients with acute ischemic...
Evaluation and subgroup analysis of the efficacy and safety of intensive rosuvastatin therapy combined with dual antiplatelet therapy in patients with acute ischemic stroke.
OBJECTIVES
We investigated the efficacy of intensive rosuvastatin therapy plus 7-day dual antiplatelet therapy (DAPT) in reducing stroke recurrence for patients with acute ischemic stroke (AIS) and compared subgroups of patients.
METHODS
We enrolled patients with AIS whose time of onset to medication was ≤ 72 h, and the baseline scores of NIHSS (bNIHSS) were 0-10. The patients received intensive rosuvastatin therapy plus 7-day DAPT with aspirin and clopidogrel (study group) or rosuvastatin plus single antiplatelet therapy (SAPT, control group). The primary outcomes were recurrence of ischemic stroke, bleeding, statin-induced liver injury, and statin-associated myopathy (SAM) within 90 days. We also performed a subgroup analysis to assess the heterogeneity of the two therapy regimens in reducing recurrent stroke.
RESULTS
Recurrent stroke occurred in 10 patients in the study group and 42 patients in the control group (hazard ratio [HR], 0.373, 95% confidence interval [CI], 0.178-0.780; P = 0.009). Bleeding events occurred in 9 patients in the study group and 14 patients in the control group (HR, 1.019; 95%CI, 0.441-2.353; P = 0.966). Statin-induced liver injury and SAM were not recorded. Intensive rosuvastatin plus 7-day DAPT was generally effective in reducing the risk of recurrent stroke, except in the subgroup with bNIHSS ≤ 2. The therapy was particularly efficient in the elderly, male, high-bNIHSS, and hypertension, diabetes, and hyperlipidemia subgroups, with P < 0.02.
CONCLUSIONS
Without increasing bleeding and statin-associated adverse events, intensive rosuvastatin therapy plus 7-day DAPT significantly reduced the risk of recurrent stroke, especially for subgroups with high-risk factors.
CLINICAL TRIAL REGISTRATION
China Clinical Trial Registration Center (ChiCTR1800017809).
Topics: Aged; Humans; Male; Chemical and Drug Induced Liver Injury, Chronic; Drug Therapy, Combination; Hemorrhage; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Rosuvastatin Calcium; Stroke; Treatment Outcome
PubMed: 36580143
DOI: 10.1007/s00228-022-03442-8 -
PloS One 2018Rosuvastatin calcium (ROSCa) is a poorly soluble drug with bioavailability not exceeding 20%. Decreasing the particle size may enhance its solubility, dissolution rate...
PURPOSE
Rosuvastatin calcium (ROSCa) is a poorly soluble drug with bioavailability not exceeding 20%. Decreasing the particle size may enhance its solubility, dissolution rate and bioavailability. Therefore, the aim of the current study is to prepare ROSCa nanoparticles by wet milling technique using planetary ball mill. The codesign between formulation and stabilization of nanoparticles was studied to achieve both high dissolution as well as bioavailability.
METHODOLOGY
ROSCa nanosuspensions was prepared by wet milling technique using planetary ball mill, by applying milling ball size of 0.1 mm at speed of 800 rpm for 3 cycles each cycle composed of 10 minutes. HPMC, PVP k-30, pluronic F-127, Tween 80 and PEG 6000 were used as stabilizers. The nanosuspensions were then freeze-dried, and the dried nanoparticles were evaluated for particle size, zeta potential, in-vitro dissolution test, XRPD and in-vivo study.
RESULTS
ROSCa nanoparticles stabilized with 10% PVP (P3) had a good stability with smallest particle size, which in turn enhanced the dissolution rate. The particle size of the leading formula was 461.8 ± 16.68 nm with zeta potential of -31.8 ± 7.22 mV compared to untreated drug that has a particle size of 618μm. The percent of ROSCa dissolved after 1 hour enhanced significantly which reached 72% and 58.25% for leading nanoparticle formula and untreated ROSCa, respectively (P < 0.05). The in-vivo study of ROSCa from the leading nanoparticle formula showed a significant enhancement in the Cmax after 2 h (82.35 ng/ml) compared to 9.2 ng/ml for untreated drug.
CONCLUSION
Wet milling technique is a successful method to prepare ROSCa nanoparticles. From different stabilizer used, PVP (10%) was able to produce stable nanoparticle with small particle size which significantly enhance the dissolution rate and pharmacokinetics parameters of ROSCa.
Topics: Animals; Anticholesteremic Agents; Biological Availability; Drug Compounding; Drug Design; Nanoparticles; Particle Size; Rabbits; Rosuvastatin Calcium
PubMed: 29985967
DOI: 10.1371/journal.pone.0200218 -
Lipids in Health and Disease Jul 2022Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid...
BACKGROUND
Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites.
METHODS
A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites.
RESULTS
A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = - 0.405 and - 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and - 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05).
CONCLUSIONS
This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic.
Topics: Atherosclerosis; Betaine; Carnitine; Cholesterol, LDL; Choline; Humans; Lipids; Methylamines; Rosuvastatin Calcium; Tandem Mass Spectrometry
PubMed: 35864500
DOI: 10.1186/s12944-022-01673-3 -
Acta Biochimica Et Biophysica Sinica May 2023Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α....
Intervertebral disc degeneration is mainly caused by irregular matrix metabolism in nucleus pulposus cells and involves inflammatory factors such as TNF-α. Rosuvastatin, which is widely used in the clinic to reduce cholesterol levels, exerts anti-inflammatory effects, but whether rosuvastatin participates in IDD remains unclear. The current study aims to investigate the regulatory effect of rosuvastatin on IDD and the potential mechanism. experiments demonstrate that rosuvastatin promotes matrix anabolism and suppresses catabolism in response to TNF-α stimulation. In addition, rosuvastatin inhibits cell pyroptosis and senescence induced by TNF-α. These results demonstrate the therapeutic effect of rosuvastatin on IDD. We further find that HMGB1, a gene closely related to cholesterol metabolism and the inflammatory response, is upregulated in response to TNF-α stimulation. HMGB1 inhibition or knockdown successfully alleviates TNF-α-induced ECM degradation, senescence and pyroptosis. Subsequently, we find that HMGB1 is regulated by rosuvastatin and that its overexpression abrogates the protective effect of rosuvastatin. We then verify that the NF-κB pathway is the underlying pathway regulated by rosuvastatin and HMGB1. experiments also reveal that rosuvastatin inhibits IDD progression by alleviating pyroptosis and senescence and downregulating HMGB1 and p65. This study might provide new insight into therapeutic strategies for IDD.
Topics: Humans; NF-kappa B; Tumor Necrosis Factor-alpha; Nucleus Pulposus; Rosuvastatin Calcium; Pyroptosis; HMGB1 Protein; Signal Transduction; Intervertebral Disc Degeneration; Cholesterol
PubMed: 37222533
DOI: 10.3724/abbs.2023026 -
Advances in Therapy Dec 2023Many patients with primary hypercholesterolemia do not achieve their plasma low-density lipoprotein cholesterol (LDL-C) goals with statin alone under a recommended dose... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Single-Pill Combination of Rosuvastatin and Ezetimibe in Chinese Patients with Primary Hypercholesterolemia Inadequately Controlled by Statin Treatment (ROZEL): A Randomized, Double-Blind, Double Dummy, Active-Controlled Phase 3 Clinical Trial.
INTRODUCTION
Many patients with primary hypercholesterolemia do not achieve their plasma low-density lipoprotein cholesterol (LDL-C) goals with statin alone under a recommended dose of statin (e.g., 10 mg rosuvastatin) in China. The objective of this phase III study was to evaluate the efficacy and safety of a new single-pill combination (SPC) of rosuvastatin 10 mg/ezetimibe 10 mg (R10/E10) in this population.
METHODS
This was a randomized, double-blind, double-dummy, active-controlled study in patients with primary hypercholesterolemia inadequately controlled with statin alone. The participants were randomized 1:1 to receive SPC R10/E10 or R10. The primary objective was to demonstrate the superiority of SPC R10/E10 vs. R10 in reducing the LDL-C levels after 8 weeks.
RESULTS
This trial randomized 305 participants to SPC R10/E10 (n = 153) and R10 (n = 152). The superiority of SPC R10/E10 over R10 was demonstrated with the least square (LS) mean difference of percent change in LDL-C from baseline to week 8: - 13.85% (95% confidence interval [CI] - 20.15% to - 7.56%, P < 0.0001). The proportion of participants who achieved the LDL-C target (< 2.6 mmol/l) at week 8 was larger with SPC R10/E10 (n = 80, 54.1%) than with R10 (n = 42, 29.2%) (Odds ratio = 2.80, 95% CI 1.70 to 4.61, P < 0.0001). No unexpected safety findings were reported.
CONCLUSION
The results suggest that SPC R10/E10 improve LDL-C reduction and goal achievement in Chinese patients with primary hypercholesterolemia not adequately controlled on statin therapy, without new safety findings.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT04669041).
Topics: Humans; Anticholesteremic Agents; Cholesterol, LDL; Double-Blind Method; East Asian People; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome; Drug Combinations
PubMed: 37770770
DOI: 10.1007/s12325-023-02666-z -
International Journal of Molecular... May 2023Atherosclerosis is driven by a diverse range of cellular and molecular processes. In the present study, we sought to better understand how statins mitigate...
Atherosclerosis is driven by a diverse range of cellular and molecular processes. In the present study, we sought to better understand how statins mitigate proatherogenic inflammation. 48 male New Zealand rabbits were divided into eight groups, each including 6 animals. The control groups received normal chow for 90 and 120 days. Three groups underwent a hypercholesterolemic diet (HCD) for 30, 60, and 90 days. Another three groups underwent HCD for 3 months, followed by normal chow for one month, with or without rosuvastatin or fluvastatin. The cytokine and chemokine expressions were assessed in the samples of thoracic and abdominal aorta. Rosuvastatin significantly reduced MYD88, CCL4, CCL20, CCR2, TNF-α, IFN-β, IL-1b, IL-2, IL-4, IL-8, and IL-10, both in the thoracic and abdominal aorta. Fluvastatin also downregulated MYD88, CCR2, IFN-β, IFN-γ, IL-1b, IL-2, IL-4, and IL-10 in both aortic segments. Rosuvastatin curtailed the expression of CCL4, IFN-β, IL-2, IL-4, and IL-10 more effectively than fluvastatin in both types of tissue. MYD88, TNF-α, IL-1b, and IL-8 showed a stronger downregulation with rosuvastatin compared to fluvastatin only in the thoracic aorta. The CCL20 and CCR2 levels reduced more extensively with rosuvastatin treatment only in abdominal aortic tissue. In conclusion, statin therapy can halt proatherogenic inflammation in hyperlipidemic animals. Rosuvastatin may be more effective in downregulating MYD88 in atherosclerotic thoracic aortas.
Topics: Male; Animals; Rabbits; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Interleukin-10; Myeloid Differentiation Factor 88; Fluvastatin; Tumor Necrosis Factor-alpha; Interleukin-2; Interleukin-4; Interleukin-8; Atherosclerosis; Aortic Diseases; Aorta, Abdominal; Inflammation; Chemokines
PubMed: 37298199
DOI: 10.3390/ijms24119248 -
Biomedicine & Pharmacotherapy =... Sep 2022The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care...
The prevalence of metabolic syndrome (MetS) has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. MetS is generally linked to complications in lipid metabolism, oxidative stress and low grade inflammation. The aim of the current study was to evaluate the effect of rosuvastatin, co-enzyme Q10 (CoQ10), and their combination on blood pressure, blood sugar, dyslipidemia, and liver function in rats with MetS induced by high fructose and high fat diet (HF-HFD) and the possible underlying mechanism. Oral administration of rosuvastatin (10 mg/kg/day), CoQ10 (10 mg/kg/day) and their combination for 4 weeks in HF-HFD-fed rats elevated serum high density lipoprotein and reduced glutathione. On the other hand, treatment with rosuvastatin, CoQ10 or their combination decreased the serum levels of malondialdehyde, triglycerides, total cholesterol, and low density lipoprotein-cholesterol as well as systolic blood pressure, body weight and fasting blood glucose level. In addition, the drugs or their combination declined serum pro-inflammatory cytokines, namely tumor necrosis factor-α and interleukin-1β. In conclusion, our results showed that rosuvastatin or CoQ10 protected against HF-HFD-induced MetS through the regulation of dyslipidemia, elevated blood glucose, elevated blood pressure, antioxidant defenses and inflammatory response. Rosuvastatin or CoQ10 also alleviated the impairment of liver function that was induced by HF-HFD. Interestingly, CoQ10 augmented rosuvastatin's effect in ameliorating MetS, via exerting synergistic modulatory effects on oxidative stress and inflammation. Thus, rosuvastatin and CoQ10 combination therapy may have possible applications in ameliorating metabolic disorders.
Topics: Animals; Blood Glucose; Cholesterol; Diet, High-Fat; Dyslipidemias; Fructose; Humans; Inflammation; Metabolic Syndrome; Oxidative Stress; Rats; Rosuvastatin Calcium
PubMed: 36076607
DOI: 10.1016/j.biopha.2022.113526 -
BMJ Open Feb 2023To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients.
DESIGN
A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up.
SETTING
Four centres in the Yale New Haven Health System.
PARTICIPANTS
Non-critically ill hospitalised patients with COVID-19.
INTERVENTIONS
Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter.
PRIMARY AND SECONDARY OUTCOME MEASURES
The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days.
RESULTS
Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17).
CONCLUSIONS
In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials.
TRIAL REGISTRATION
NCT04472611.
Topics: Female; Humans; Middle Aged; Male; COVID-19; Rosuvastatin Calcium; SARS-CoV-2; Colchicine; Brain Ischemia; Stroke; Treatment Outcome
PubMed: 36828654
DOI: 10.1136/bmjopen-2022-067910