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American Journal of Cardiovascular... Aug 2020Rosuvastatin/ezetimibe combines two lipid-lowering agents: rosuvastatin, an HMG-CoA reductase inhibitor (i.e. statin) with particularly strong inhibitory effects on... (Review)
Review
Rosuvastatin/ezetimibe combines two lipid-lowering agents: rosuvastatin, an HMG-CoA reductase inhibitor (i.e. statin) with particularly strong inhibitory effects on hepatic cholesterol synthesis, and ezetimibe, which inhibits the intestinal absorption of cholesterol. A fixed-dose combination (FDC) of rosuvastatin/ezetimibe is indicated as an adjunctive therapy to diet for the management of primary hypercholesterolemia in adults in numerous countries worldwide. In well-designed clinical trials evaluating the therapeutic efficacy of rosuvastatin/ezetimibe administered as either separate agents or as an FDC, rosuvastatin/ezetimibe was significantly more effective than rosuvastatin monotherapy (including at double the dose of rosuvastatin) or simvastatin/ezetimibe in reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol in adults with hypercholesterolemia. Furthermore, rosuvastatin/ezetimibe enabled significantly higher proportions of patients to achieve recommended LDL-C levels than rosuvastatin monotherapy or simvastatin/ezetimibe. Rosuvastatin/ezetimibe did not significantly differ from rosuvastatin monotherapy with respect to incidences of treatment-related or serious adverse events in these short-term trials and displayed a similar safety profile to simvastatin/ezetimibe. While additional cardiovascular outcomes data and head-to-head comparisons with atorvastatin/ezetimibe would be of interest, rosuvastatin/ezetimibe is a potent and generally well-tolerated drug combination that extends the range of options available for the pharmacological management of primary hypercholesterolemia in adults.
Topics: Anticholesteremic Agents; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Humans; Hypercholesterolemia; Rosuvastatin Calcium
PubMed: 32648167
DOI: 10.1007/s40256-020-00421-1 -
Drug Design, Development and Therapy 2022Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One... (Review)
Review
Cardiovascular disease is one of the leading causes of death around the world with various efforts being made to reduce risk in patients through preventive measures. One major method for prevention has been managing cholesterol, particularly low-density lipoprotein to decrease atherosclerotic plaque burden, potentially decreasing future cardiac complications. Statins have been the gold standard therapy for hypercholesterolemia treatment due to their ease of dosing, limited drug interactions, and favorable safety profile. Unfortunately, statin therapy alone is not always effective enough to adequately control a patient's elevated lipid levels and combination therapy may be warranted. Ezetimibe is commonly added to regimens to help augment cholesterol lowering by inhibiting the absorption of cholesterol. The recent approval of a combination tablet of high-intensity rosuvastatin and ezetimibe has introduced a potentially more beneficial option for cholesterol management in addition to the only available combination of moderate intensity simvastatin and ezetimibe. We aimed to identify potential beneficial effects of ezetimibe by comparing its use in combination with high-intensity rosuvastatin compared to a statin therapy alone or in combination with moderate intensity simvastatin through a literature review. The current evidence indicated that combination therapy outperformed statin monotherapy in reduction of low-density lipoprotein cholesterol and patients were more likely to achieve their target low-density lipoprotein cholesterol goal level. This suggests rosuvastatin/ezetimibe combination holds a potential place in therapy for patients requiring a more aggressive reduction in cholesterol to help prevent atherosclerotic disease.
Topics: Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Drug Therapy, Combination; Dyslipidemias; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Simvastatin; Treatment Outcome
PubMed: 35832642
DOI: 10.2147/DDDT.S332352 -
Stroke Oct 2022Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events.
METHODS
This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed.
RESULTS
Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, -0.0023-0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080-0.0204) for the placebo group, with a difference of -0.0103 mm/y (95% CI, -0.0191 to -0.0016; =0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin.
CONCLUSIONS
Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT02546323.
Topics: Adult; Atherosclerosis; Cardiovascular Diseases; Carotid Arteries; Carotid Artery Diseases; Carotid Intima-Media Thickness; Disease Progression; Fluorobenzenes; Humans; Lipids; Pyrimidines; Rosuvastatin Calcium; Sulfonamides
PubMed: 36017704
DOI: 10.1161/STROKEAHA.120.031877 -
JAMA Apr 2023In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease.
OBJECTIVE
To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.
DESIGN, SETTING, AND PARTICIPANTS
A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022).
INTERVENTIONS
Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.
MAIN OUTCOMES AND MEASURES
Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points.
RESULTS
Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority).
CONCLUSIONS AND RELEVANCE
Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02579499.
Topics: Aged; Female; Humans; Cholesterol, LDL; Coronary Artery Disease; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Stroke; Treatment Outcome; Hyperlipoproteinemias; Male; Middle Aged; Rosuvastatin Calcium; Atorvastatin
PubMed: 36877807
DOI: 10.1001/jama.2023.2487 -
Journal of Clinical Hypertension... Oct 2020Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more... (Randomized Controlled Trial)
Randomized Controlled Trial
Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.
Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypertension; Male; Middle Aged; Rosuvastatin Calcium; Telmisartan
PubMed: 32937023
DOI: 10.1111/jch.13893 -
Herz Sep 2020The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population.
METHODS
The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model.
RESULTS
The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events.
CONCLUSION
Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.
Topics: Atorvastatin; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome
PubMed: 30483816
DOI: 10.1007/s00059-018-4767-2 -
PloS One 2022This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal...
This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal was to ensure rapid disintegration and high dissolution rate of the active ingredient, thus enhancing its bioavailability. The design started from a careful selection of excipients, which due to their characteristics and proportions within the formulation allowed the use of their properties such as fluidity or granulometric distribution. The formulation was characterised using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) methods. The galenic SeDeM methodology was used to establish the profile of the active ingredient-excipient mixture and guarantee its suitability for producing tablets by the direct compression method. The results demonstrate that the amorphous rosuvastatin calcium tablets formulation developed made it possible to obtain cost-effective tablets by direct compression with optimal pharmacotechnical characteristics that showed a remarkable disintegration and dissolution rate. The manufactured tablets complied with the pharmacopoeia guidelines regarding content uniformity, tablet hardness, thickness, friability, in vitro disintegration time and dissolution profile.
Topics: Calcium; Calorimetry, Differential Scanning; Excipients; Rosuvastatin Calcium; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets; X-Ray Diffraction
PubMed: 35312730
DOI: 10.1371/journal.pone.0265263 -
Journal of Comparative Effectiveness... Mar 2023To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic... (Meta-Analysis)
Meta-Analysis Review
To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Atorvastatin; Cohort Studies
PubMed: 36847307
DOI: 10.57264/cer-2022-0163 -
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 -
Pharmacological Research May 2016Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the... (Review)
Review
Rosuvastatin is a fully synthetic statin wich acts by interfering with the endogenous synthesis of cholesterol through competitively inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase, a liver enzyme responsible of the rate-limiting step in cholesterol synthesis. When compared to other molecules of the same class, it shows high efficacy in the improvement of lipid profile, and, thanks to its non-cholesterol-lowering actions (anti-inflammatory, antioxidant and antithrombotic), represents a crucial tool for cardiovascular primary and secondary prevention. Moreover, recent data highlight rosuvastatin beneficial effects in several other fields. In this manuscript we analyzed literature sources in order to better define rosuvastatin features and discuss some critical issues.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Cholesterol; Fibrinolytic Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
PubMed: 26930419
DOI: 10.1016/j.phrs.2016.02.012