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1.
Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.
Rollefstad, S, Ikdahl, E, Hisdal, J, Olsen, IC, Holme, I, Hammer, HB, Smerud, KT, Kitas, GD, Pedersen, TR, Kvien, TK, et al
Arthritis & rheumatology (Hoboken, N.J.). 2015;(7):1718-28
Abstract
OBJECTIVE Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. METHODS Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. RESULTS The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. CONCLUSION Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.
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2.
The effect of rosuvastatin on platelet-leukocyte interactions in the setting of acute coronary syndrome.
Sexton, TR, Wallace, EL, Macaulay, TE, Charnigo, RJ, Evangelista, V, Campbell, CL, Bailey, AL, Smyth, SS
Journal of the American College of Cardiology. 2015;(3):306-7
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3.
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial.
Hovingh, GK, Kastelein, JJ, van Deventer, SJ, Round, P, Ford, J, Saleheen, D, Rader, DJ, Brewer, HB, Barter, PJ
Lancet (London, England). 2015;(9992):452-60
Abstract
BACKGROUND Dyslipidaemia remains a significant risk factor for cardiovascular disease and additional lipid-modifying treatments are warranted to further decrease the cardiovascular disease burden. We assessed the safety, tolerability and efficacy of a novel cholesterol esterase transfer protein (CETP) inhibitor TA-8995 in patients with mild dyslipidaemia. METHODS In this randomised, double-blind, placebo-controlled, parallel-group phase 2 trial, we recruited patients (aged 18-75 years) from 17 sites (hospitals and independent clinical research organisations) in the Netherlands and Denmark with fasting LDL cholesterol levels between 2·5 mmol/L and 4·5 mmol/L, HDL cholesterol levels between 0·8 and 1·8 mmol/L and triglyceride levels below 4·5 mmol/L after washout of lipid-lowering treatments. Patients were randomly allocated (1:1) by a computer-generated randomisation schedule to receive one of the following nine treatments: a once a day dose of 1 mg, 2·5 mg, 5 mg, or 10 mg TA-8995 or matching placebo; 10 mg TA-8995 plus 20 mg atorvastatin; 10 mg TA-8995 plus 10 mg rosuvastatin or 20 mg atorvastatin or 10 mg rosuvastatin alone. We overencapsulated statins to achieve masking. The primary outcome was percentage change in LDL cholesterol and HDL cholesterol from baseline at week 12, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01970215. FINDINGS Between Aug 15, 2013, and Jan 10, 2014, 364 patients were enrolled. At week 12, LDL cholesterol levels were reduced by 27·4% in patients assigned to the 1 mg dose, 32·7% in patients given the 2·5 mg dose, 45·3% in those given the 5 mg dose, and 45·3% in those given the 10 mg dose (p<0·0001). LDL cholesterol levels were reduced by 68·2% in patients given 10 mg TA-8995 plus atorvastatin, and by 63·3% in patients given rosuvastatin plus 10 mg TA-8995 (p<0·0001). A daily dose of 1 mg TA-8995 increased HDL cholesterol levels by 75·8%, 2·5 mg by 124·3%, 5 mg by 157·1%, and 10 mg dose by 179·0% (p<0·0001). In patients receiving 10 mg TA-8995 and 20 mg atorvastatin HDL cholesterol levels increased by 152·1% and in patients receiving 10 mg TA-8995 and 10 mg rosuvastatin by 157·5%. We recorded no serious adverse events or signs of liver or muscle toxic effects. INTERPRETATION TA-8995, a novel CETP inhibitor, is well tolerated and has beneficial effects on lipids and apolipoproteins in patients with mild dyslipidaemia. A cardiovascular disease outcome trial is needed to translate these effects into a reduction of cardiovascular disease events. FUNDING Dezima.
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4.
Comparison of the efficacy of rosuvastatin versus atorvastatin in preventing contrast induced nephropathy in patient with chronic kidney disease undergoing percutaneous coronary intervention.
Liu, Y, Liu, YH, Tan, N, Chen, JY, Zhou, YL, Li, LW, Duan, CY, Chen, PY, Luo, JF, Li, HL, et al
PloS one. 2014;(10):e111124
Abstract
OBJECTIVES We prospectively compared the preventive effects of rosuvastatin and atorvastatin on contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). METHODS We enrolled 1078 consecutive patients with CKD undergoing elective PCI. Patients in Group 1 (n = 273) received rosuvastatin (10 mg), and those in group 2 (n = 805) received atorvastatin (20 mg). The primary end-point was the development of CIN, defined as an absolute increase in serum creatinine ≥0.5 mg/dL, or an increase ≥25% from baseline within 48-72 h after contrast medium exposure. RESULTS CIN was observed in 58 (5.4%) patients. The incidence of CIN was similar in patients pretreated with either rosuvastatin or atorvastatin (5.9% vs. 5.2%, p = 0.684). The same results were also observed when using other definitions of CIN. Clinical and procedural characteristics did not show significant differences between the two groups (p>0.05). Additionally, there were no significant inter-group differences with respect to in-hospital mortality rates (0.4% vs. 1.5%, p = 0.141), or other in-hospital complications. Multivariate logistic regression analysis revealed that rosuvastatin and atorvastatin demonstrated similar efficacies for preventing CIN, after adjusting for potential confounding risk factors (odds ratio = 1.17, 95% confidence interval, 0.62-2.20, p = 0.623). A Kaplan-Meier survival analysis showed that patients taking either rosuvastatin or atorvastatin had similar incidences of all-cause mortality (9.4% vs. 7.1%, respectively; p = 0.290) and major adverse cardiovascular events (29.32% vs. 23.14%, respectively; p = 0.135) during follow-up. CONCLUSIONS Rosuvastatin and atorvastatin have similar efficacies for preventing CIN in patients with CKD undergoing PCI.
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5.
Comparison of atorvastatin, pitavastatin and rosuvastatin for residual cardiovascular risk using non-fasting blood sampling.
Kakuda, H, Matoba, M, Nakatoh, H, Nagao, S, Takekoshi, N
Scandinavian journal of clinical and laboratory investigation. 2014;(4):285-95
Abstract
BACKGROUND Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk. However, some patients show symptoms of coronary heart disease (CHD) even though their LDL-C is strictly controlled. Therefore, it is important to treat other risk factors. METHODS Some 129 outpatients with dyslipidemia who were treated with either atorvastatin 10 mg/day (ATO), pitavastatin 2 mg/day (PIT), or rosuvastatin 2.5 mg/day (ROS) were enrolled. After informed consent was obtained, these patients were switched to another statin. Lipid profiles and lipoprotein fraction by polyacrylamide gel electrophoresis (PAGE) were compared between before and after 3 months of treatment with non-fasting blood sample. RESULTS LDL-C did not show any significant changes after switching and was maintained around 2.59 mmol/L in all groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in group ATO→PIT (1.43→1.54 mmol/L, p = 0.0010) and ROS→PIT (1.46→1.57 mmol/L, p = 0.0004), and was significantly decreased in group PIT→ATO (1.44→1.36 mmol/L, p = 0.0290). Apolipoprotein A-I (Apo A-I) and preheparin lipoprotein lipase (LPL) mass showed similar changes in HDL-C. Changes in HDL-C showed a significant positive correlation with those in Apo A-I and preheparin LPL mass, and a little but significant negative correlation with changes in Lp(a) and intermediate density lipoprotein (IDL) fraction. CONCLUSIONS ATO, PIT, and ROS have comparable effect on LDL-C lowering. Changes in HDL-C were similar to those in Apo A-I and preheparin LPL mass, and PIT was the most effective treatment in increasing HDL-C, Apo A-I, and preheparin LPL mass.
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6.
Design of the rosuvastatin pretreatment to reduce embolization during Carotid Artery Stenting trial.
De Carlo, M, Cortese, B, Pennesi, M, Misuraca, L, Conte, L, Pitì, A, Petronio, AS, Balbarini, A
Journal of cardiovascular medicine (Hagerstown, Md.). 2014;(7):595-600
Abstract
BACKGROUND Carotid artery stenting (CAS) is a worldwide diffuse intervention, but may be associated with distal plaque component embolization, and sometimes major and minor stroke. Statin use has been demonstrated to reduce atherosclerotic plaque burden, but its effect in reducing distal embolization during carotid stenting has not yet been well validated. AIMS With the Rosuvastatin Pretreatment to Reduce Embolization during Carotid Artery Stenting trial, we aim to discover if a pretreatement with high doses of rosuvastatin in dyslipidemic patients is able to reduce periprocedural cerebral ischemic complications following carotid stenting. METHODS This is a phase III prospective, randomized controlled trial. All consecutive patients with asymptomatic carotid stenosis at least 80% will be randomized to a 6-week rosuvastatin treatment followed by carotid stenting, and to direct carotid stenting. Carotid stenting will be performed following common practice with distal or proximal embolic protection. The primary efficacy end point of the trial will be the prevalence of 'relevant' embolization during CAS, as a surrogate end point for cerebral ischemic complications. Other laboratory and clinical data will be registered and patients will be followed up to 1 year. In order to obtain the expected superiority of statin pretreatment on primary end point, a population of 130 patients will be enrolled into the study. CONCLUSION In conclusion, with the Rosuvastatin Pretreatment to Reduce Embolization during Carotid Artery Stenting trial, we want to evaluate whether a high dose of rosuvastatin for 6 weeks before CAS in asymptomatic patients with severe carotid stenosis is able to reduce the rate of plaque embolization during the procedure, thus suggesting a possible reduction in cerebral ischemic complications.
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7.
Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies.
Robinson, JG, Colhoun, HM, Bays, HE, Jones, PH, Du, Y, Hanotin, C, Donahue, S
Clinical cardiology. 2014;(10):597-604
Abstract
The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20-40 mg/d) or rosuvastatin (10-20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20-40 mg) or rosuvastatin (10-20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level.
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8.
Anti-inflammatory effects of rosuvastatin in healthy subjects: a prospective longitudinal study.
McGuire, TR, Kalil, AC, Dobesh, PP, Klepser, DG, Olsen, KM
Current pharmaceutical design. 2014;(7):1156-60
Abstract
AIMS: The aims of this study were to determine a mechanism and general timeline for statin related anti-inflammatory activity. METHODS Healthy male subjects received rosuvastatin (20 mg daily) for 3 weeks. Blood samples before and after treatment were collected for clinical laboratories and research procedures. Toll-like receptor-4 (tlr-4) expression on blood monocytes was measured using flow cytometry before and after rosuvastatin treatment. Inflammatory molecules were measured before and after rosuvastatin and after blood samples were incubated for 3 hours with or without lipopolysaccharide. Plasma was collected and analyzed for IL-6, TNF-α, IL-8, IGF-1, and sCD14. Comparisons were made using Mann-Whitney rank sum test and paired Student's t-test with significance defined as p≤0.05. KEY FINDINGS The expression oftlr-4on blood monocytes was significantly lower after 3 weeks of rosuvastatin (p = 0.046). Consistent with the reduced expression of tlr-4, the TNF-α release from blood receiving LPS trended lower (p = 0.08). None of the other inflammatory markers (IL-8, sCD14, IL-6, IGF-1, C-reactive protein) were modified with rosuvastatin treatment. There were significant declines in total cholesterol (p<0.0001), low-density lipoprotein cholesterol (LDL-C) (p<0.0001), and total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio (p<0.0001) after 3 weeks of treatment. There was no significant effect on triglycerides, very low-density lipoprotein cholesterol (VLDL-C), or HDL-C. SIGNIFICANCE The decline in tlr-4 expression on blood monocytes and TNF-α plasma concentrations after 3 weeks of rosuvastatin treatment suggest a potential mechanism for the anti-inflammatory activity of rosuvastatin.
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9.
Differences between rosuvastatin and atorvastatin in lipid-lowering action and effect on glucose metabolism in Japanese hypercholesterolemic patients with concurrent diabetes. Lipid-lowering with highly potent statins in hyperlipidemia with type 2 diabetes patients (LISTEN) study –.
Ogawa, H, Matsui, K, Saito, Y, Sugiyama, S, Jinnouchi, H, Sugawara, M, Masuda, I, Mori, H, Waki, M, Yoshiyama, M, et al
Circulation journal : official journal of the Japanese Circulation Society. 2014;(10):2512-5
Abstract
BACKGROUND Little is known about the differences between standard-dose statins effects on glucose level and lipids in Japanese patients with diabetes mellitus (DM). METHODS AND RESULTS The 1,049 patients were randomly assigned to either the rosuvastatin group or atorvastatin group. There were no significant differences between the 2 groups in the effect on non-high-density lipoprotein cholesterol (non-HDL-C) and HbA1c at 12 months. However, physicians tended to switch to more intensive therapy for DM in the atorvastatin group. CONCLUSIONS Rosuvastatin 5 mg and atorvastatin 10 mg have a similar lowering effect on non-HDL-C, but might be different in terms of adverse effect on glucose levels.
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10.
Early decrease in carotid plaque lipid content as assessed by magnetic resonance imaging during treatment of rosuvastatin.
Du, R, Cai, J, Zhao, XQ, Wang, QJ, Liu, DQ, Leng, WX, Gao, P, Wu, HM, Ma, L, Ye, P
BMC cardiovascular disorders. 2014;:83
Abstract
BACKGROUND Statin therapy has shown to deplete atherosclerotic plaque lipid content and induce plaque regression. However, how early the plaque lipid depletion can occur with low-density lipoprotein cholesterol (LDL-C) lowering in humans in vivo has not been fully described. METHODS We enrolled 43 lipid treatment naïve subjects with asymptomatic carotid atherosclerosis and LDL-C ≥ 100 and ≤ 250 mg/dl. Rosuvastatin 5-20 mg/day was used to lower LDL-C levels to < 80 mg/dl. Lipid profile and carotid MRI scans were obtained at baseline, 3, 12, and 24 months. Carotid plaque lipid-rich necrotic core (LRNC) and plaque burden were measured and compared between baseline and during treatment. RESULTS Among the 32 subjects who completed the study, at 3 months, an average dose of rosuvastatin of 11 mg/day lowered LDL-C levels by 47% (125.2 ± 24.4 mg/dl vs. 66.7 ± 17.3 mg/dl, p < 0.001). There were no statistically significant changes in total wall volume, percent wall volume or lumen volume. However, LRNC volume was significantly decreased by 7.9 mm3, a reduction of 7.3% (111.5 ± 104.2 mm3 vs. 103.6 ± 95.8 mm3, p = 0.044). Similarly, % LRNC was also significantly decreased from 18.9 ± 11.9% to 17.9 ± 11.5% (p = 0.02) at 3 months. Both LRNC volume and % LRNC continued to decrease moderately at 12 and 24 months, although this trend was not significant. CONCLUSIONS Among a small number of lipid treatment naïve subjects, rosuvastatin therapy may induce a rapid and lasting decrease in carotid plaque lipid content as assessed by MRI. TRIAL REGISTRATION ClinicalTrials.Gov numbers NCT00885872.