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Effects of randomized rosuvastatin compared with placebo on bone and body composition among HIV-infected adults.
Erlandson, KM, Jiang, Y, Debanne, SM, McComsey, GA
AIDS (London, England). 2015;(2):175-82
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BACKGROUND Statins have a beneficial effect on bone mineral density (BMD) and lean mass in some studies of HIV-uninfected adults; however, this has never been investigated in the setting of HIV infection. DESIGN HIV-infected individuals on stable antiretroviral therapy with a low-density lipoprotein cholesterol level of 130 mg/dl or less and evidence of heightened immune activation or inflammation were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. METHODS This was a prespecified interim analysis at 48 weeks. Between-group and within-group differences were compared; multivariable regression models were constructed. RESULTS Seventy-two individuals were randomized to statin therapy and 75 to placebo. Modest 48-week relative increases in trochanter BMD [0.9%; 95% confidence interval (95% CI) -0.9 to 0.6] and total hip BMD (0.6%; 95% CI 0.0-1.1) in the statin arm were significantly greater than placebo (P < 0.05). The relationship between statin use and total hip BMD change was robust to adjustment of age, sex, race and smoking status (P = 0.02) and strengthened by inclusion of baseline (P = 0.01) and week 48 change in soluble tumour necrosis factor-α receptor (sTNFR)-1 (P = 0.009). Relative increases in total body, trunk and limb fat were similar between statin and placebo arms (P ≥ 0.58). Although a significant gain in leg lean mass was seen in the statin arm, this was not significantly different compared with placebo (P = 0.36). CONCLUSION The improvements seen in total hip BMD after 48 weeks of rosuvastatin therapy support further potential benefits of statin therapy in HIV, beyond a reduction of cardiovascular risk.
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Rosuvastatin treatment in stable chronic obstructive pulmonary disease (RODEO): a randomized controlled trial.
Neukamm, A, Høiseth, AD, Einvik, G, Lehmann, S, Hagve, TA, Søyseth, V, Omland, T
Journal of internal medicine. 2015;(1):59-67
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OBJECTIVES The objective of this study was to examine whether statin therapy is associated with enhanced endothelium-dependent vascular function, improved pulmonary function and reduced systemic inflammation in patients with chronic obstructive pulmonary disease (COPD). DESIGN AND SETTING This randomized, placebo-controlled, double-blind, parallel trial including patients with COPD was performed at two University hospitals in Norway. SUBJECTS, INTERVENTION AND MEASUREMENTS Patients with stable COPD (n = 99) were assigned randomly to receive rosuvastatin 10 mg (n = 49) or matching placebo (n = 50) once daily for 12 weeks. The primary outcome measure was change in endothelium-dependent vascular function measured using peripheral arterial tonometry and expressed as the reactive hyperaemia index. Secondary end-points were change in pulmonary function, as assessed by forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC), and change in the circulating levels of the inflammatory markers interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP). RESULTS In the overall study population, no significant between-group difference in change in endothelium-dependent vascular or pulmonary function was observed. Rosuvastatin therapy was associated with a reduction in hsCRP (-20% vs. 11%, P = 0.017) and an attenuation of the rise in IL6 concentration (8% vs. 30%, P = 0.028) compared with placebo. In a prespecified subgroup analysis of patients with a supra-median circulating hsCRP concentration (>1.7 mg L(-1) ), rosuvastatin was associated with improved endothelium-dependent vascular function (13% vs. 2%, P = 0.026). CONCLUSIONS In stable COPD patients without the standard indications for statin therapy, rosuvastatin treatment is associated with a significant attenuation of systemic inflammation and improvement in endothelial-dependent vascular function in patients with evidence of systemic inflammation.
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Association of Plasma Ceramides and Sphingomyelin With VLDL apoB-100 Fractional Catabolic Rate Before and After Rosuvastatin Treatment.
Ng, TW, Ooi, EM, Watts, GF, Chan, DC, Meikle, PJ, Barrett, PH
The Journal of clinical endocrinology and metabolism. 2015;(6):2497-501
Abstract
INTRODUCTION The objective of the study was to examine post hoc associations between plasma sphingolipids and lipoprotein kinetics in men with the metabolic syndrome after rosuvastatin treatment. MATERIALS AND METHODS Plasma sphingolipid profiling, determined by tandem mass spectrometry, was performed in a randomized, double-blind, triple-crossover trial (n = 12) of 5-week treatment periods with placebo or rosuvastatin (10 or 40 mg/d) with 2-week washouts between treatments. RESULTS AND DISCUSSION Baseline plasma ceramides were associated with very low-density lipoprotein (VLDL) apolipoprotein (apo)-B-100 concentration (r = 0.58, P < .05) and inversely with VLDL apoB-100 fractional catabolic rate (FCR; r = -0.67, P = .02). Posttreatment changes with rosuvastatin (40 mg/d) in plasma ceramides were inversely associated with VLDL apoB-100 FCR (r = -0.62, P = .03) independent of changes in plasma triglycerides, cholesterol, and low-density lipoprotein-cholesterol. By contrast, baseline and postrosuvastatin treatment plasma sphingomyelin levels were not associated with apoB-100 kinetics. Plasma ceramides and sphingomyelin were not associated with the kinetics or concentrations of high-density lipoprotein apoA-I, and low-density lipoprotein apoB. In the metabolic syndrome, the ability of rosuvastatin to increase VLDL apoB-100 FCR may reflect ceramide-specific mechanistic actions and/or sphingolipid exchange.
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Statin therapy and risk of fracture: results from the JUPITER randomized clinical trial.
Peña, JM, Aspberg, S, MacFadyen, J, Glynn, RJ, Solomon, DH, Ridker, PM
JAMA internal medicine. 2015;(2):171-7
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IMPORTANCE Osteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant. OBJECTIVE To determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture. DESIGN, SETTING, AND PARTICIPANTS The JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17,802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2 mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years). INTERVENTION Rosuvastatin calcium, 20 mg daily, or placebo. MAIN OUTCOMES AND MEASURES Incident fracture was a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95% confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders. RESULTS During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95% CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95% CI, 0.94-1.20]; P for trend, .34). CONCLUSIONS AND RELEVANCE Among men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00239681.
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[Comparative Randomized Study of the Effects of Long-Term Therapy With Rosuvastatin and Combination of Atorvastatin and Ezetimibe on Carbohydrate Metabolism and Adipokines Levels in Patients With Coronary Artery Disease and Diabetes Mellitus].
Koshel'skaia, OA, Vinnitskaia, IV, Konko, TIu, Kravchenko, ES, Suslova, TE, Karpov, RS
Kardiologiia. 2015;(3):67-74
Abstract
OBJECTIVE This open randomized study compares the effects of 24-week-long treatment with rosuvastatin and with atorvastatin coadministered with ezetimibe on the parameters of carbohydrate metabolism and the plasma levels of adipokynes in patients with coronary artery disease and type 2 diabetes mellitus or impaired glucose tolerance (IGT). METHOD A total of 31 patients with coronary artery disease and type 2 diabetes mellitus or IGT were recruited in the study. Patients were randomized into two groups: group 1 included patients who received rosuvastatin therapy in an average dose of 12.5 mg/day (n = 16); group 2 included patients who received combination treatment with atorvastatin in an average dose of 13.3 mg/day and ezetimibe (10 mg) (n = 15). Plasma levels of lipids, apoB, apoA1, glucose, insulin, leptin, and adiponectin were evaluated; HOMA-IR index (an empty stomach insulin, mu/l x fasting glucose, mmol/l)/22.5) was calculated. RESULTS During the therapy, the LDL-C and apoB levels decreased by 51.7% and 42.3% in group 1 and by 51.8% and 44.9% in group 2, respectively. Reduction in the triglyceride levels was significantly more pronounced in group 2 than in group 1: 43.2% vs 17.4% (p < 0.02), whereas we did not observed significant changes of HDL-C and apoA1 in either group. The increases in basal glycemia, basal insulinemia, HbA1c levels (from 6.47% [6.10-7.02%] to 6.98% 16.23-8.18%]), and HOMA-IR (from 2.14 [1.68-3.51] to 4.30 [2.31-5.77]) were found only in group 2 (p < 0.05 for all). These changes were observed in 75% of patients of group 2 independently of the presence of diabetic state or IGT, but the changes were more pronounced in patients with disturbed carbohydrate metabolism. Changes of leptin levels during the therapy were diverse: 73% patients of group 1 demonstrated decrease in the leptin levels, whereas 67% of patients in group 2 experienced 57%-increase in the leptin concentrations. Degree of increased basal glycemia was associated with increase in the leptin levels (r = 0.37, p = 0.04) in the entire group of patients (n = 31). Furthermore, changes in leptin levels were negatively associated with decreased adiponectin levels (r = -0.57, p = 0.034). CONCLUSIONS In case of equivalent degree of the decrease in LDL-C levels, 24-week combination therapy with atorvastatin and ezetimibe, unlike rosuvastatin treatment, induced increases in basal glycemia, insulinemia, HbA1c, and HOMA-IR index irrespective of the presence of carbohydrate metabolism disturbances before treatment. Our data suggest that adiponectin and leptin are involved in the mechanisms of adverse metabolic effects of the combination of atorvastatin and ezetimibe.
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Preoperative rosuvastatin protects patients with coronary artery disease undergoing noncardiac surgery.
Xia, J, Qu, Y, Yin, C, Xu, D
Cardiology. 2015;(1):30-7
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OBJECTIVES We explored whether preoperative rosuvastatin could protect the cardiac health of patients with coronary artery disease undergoing emergency, noncardiac surgery. METHODS We randomized 550 noncardiac emergency surgery patients with stable coronary artery disease on long-term statin therapy to treatment with and without preoperative rosuvastatin. All patients received rosuvastatin after surgery. We evaluated the incidence of myocardial necrosis and major adverse cardiovascular and cerebrovascular events (MACCE) 30 days and 6 months after surgery. RESULTS Creatinine kinase-myocardial band (CK-MB) isoform elevations occurred less frequently 12 and 24 h after noncardiac emergency surgery in the experimental group than in the control group (p = 0.029). After surgery, the incidence of MACCE was also lower in the experimental group than in the control group (p = 0.019). The difference was mainly due to the incidence of perioperative myocardial infarction (p = 0.029). Multivariable analysis found that rosuvastatin reload reduced the incidence of MACCE 52% 6 months after surgery (p = 0.03). CONCLUSIONS Preoperative rosuvastatin reload therapy decreases the incidence of myocardial necrosis and MACCE after noncardiac emergency surgery in patients with stable coronary artery disease on long-term statin therapy.
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Combining rosuvastatin with angiotensin-receptor blockers of different PPARγ-activating capacity: effects on high-density lipoprotein subfractions and associated enzymes.
Rizos, CV, Liberopoulos, EN, Tellis, K, DiNicolantonio, JJ, Tselepis, AD, Elisaf, MS
Angiology. 2015;(1):36-42
Abstract
The effects of combining angiotensin-receptor blockers of different peroxisome proliferator-activated receptor γ-activating capacity with rosuvastatin on high-density lipoprotein (HDL) subfractions and associated enzymes in patients with mixed dyslipidemia, hypertension, and prediabetes were assessed. Patients (n = 151) were randomly allocated to rosuvastatin (10 mg/d) plus telmisartan 80 mg/d (RT group, n = 52) or irbesartan 300 mg/d (RI group, n = 48) or olmesartan 20 mg/d (RO group, n = 51). Total and intermediate HDL cholesterol (HDL-C) levels did not change in any group. Large HDL-C increased, while small HDL-C decreased significantly in all the groups (P = not significant between the groups). The mass of HDL lipoprotein-associated phospholipase A2 (HDL-Lp-PLA2) and the activities of paraoxonase 1 remained unchanged in all the groups. However, HDL-Lp-PLA2 activity increased only in the RT group (+21.4%; P < .01 vs baseline) and did not change in the RI (-4.3%; P = .005 vs RT group) and RO (+3.2%; P = .01 vs RT) groups. In conclusion, only the combination of rosuvastatin with telmisartan increased the possibly antiatherosclerotic HDL-Lp-PLA2 activity.
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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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Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in patients with coronary artery disease.
Masuda, J, Tanigawa, T, Yamada, T, Nishimura, Y, Sasou, T, Nakata, T, Sawai, T, Fujimoto, N, Dohi, K, Miyahara, M, et al
International heart journal. 2015;(3):278-85
Abstract
Ezetimibe has been reported to provide significant incremental reduction in low-density-lipoprotein cholesterol (LDL-C) when added to a statin; however, its effect on coronary atherosclerosis has not yet been evaluated in detail. The aim of this study was to investigate the add-on effect of ezetimibe to a statin on coronary atherosclerosis evaluated by intravascular ultrasound (IVUS).In this prospective randomized open-label study, a total of 51 patients with stable coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI) were enrolled, and assigned to a combination group (n = 26, rosuvastatin 5 mg/day + ezetimibe 10 mg/day) or a monotherapy group (n = 25, rosuvastatin 5 mg/day). Volumetric IVUS analyses were performed at baseline and 6 months after the treatment for a non-PCI site. LDL-C level was significantly reduced in the combination group (-55.8%) versus that in the monotherapy group (-36.8%; P = 0.004). The percent change in plaque volume (PV), the primary endpoint, appeared to decrease more effectively in the combination group compared with the monotherapy group (-13.2% versus -3.1%, respectively, P = 0.050). Moreover, there was a significant group × time interaction in the effects of the two treatments on PV (P = 0.021), indicating the regressive effect of the combination therapy on PV was greater than that of monotherapy for subtly different values of baseline PV in the two treatment groups. Moreover, percent change in PV showed positive correlations with percent change of LDL-C (r = 0.384, P = 0.015).Intensive lipid-lowering therapy with ezetimibe added to usual-dose statin may provide significant incremental reduction in coronary plaques compared with usual-dose statin monotherapy.
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International geographic variation in event rates in trials of heart failure with preserved and reduced ejection fraction.
Kristensen, SL, Køber, L, Jhund, PS, Solomon, SD, Kjekshus, J, McKelvie, RS, Zile, MR, Granger, CB, Wikstrand, J, Komajda, M, et al
Circulation. 2015;(1):43-53
Abstract
BACKGROUND International geographic differences in outcomes may exist for clinical trials of heart failure and reduced ejection fraction (HF-REF), but there are few data for those with preserved ejection fraction (HF-PEF). METHODS AND RESULTS We analyzed outcomes by international geographic region in the Irbesartan in Heart Failure with Preserved systolic function trial (I-Preserve), the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved trial, the CHARM-Alternative and CHARM-Added HF-REF trials, and the Controlled Rosuvastatin Multinational Trial in HF-REF (CORONA). Crude rates of heart failure hospitalization varied by geographic region, and more so for HF-PEF than for HF-REF. Rates in patients with HF-PEF were highest in the United States/Canada (HF hospitalization rate 7.6 per 100 patient-years in I-Preserve; 8.8 in CHARM-Preserved), intermediate in Western Europe (4.8/100 and 4.7/100), and lowest in Eastern Europe/Russia (3.3/100 and 2.8/100). The difference between the United States/Canada versus Eastern Europe/Russia persisted after adjustment for key prognostic variables: adjusted hazard ratios 1.34 (95% confidence interval, 1.01-1.74; P=0.04) in I-Preserve and 1.85 (95% confidence interval, 1.17-2.91; P=0.01) in CHARM-Preserved. In HF-REF, rates of HF hospitalization were slightly lower in Western Europe compared with other regions. For both HF-REF and HF-PEF, there were few regional differences in rates of all-cause or cardiovascular mortality. CONCLUSIONS The differences in event rates observed suggest there is international geographic variation in 1 or more of the definition and diagnosis of HF-PEF, the risk profile of patients enrolled, and the threshold for hospitalization, which has implications for the conduct of future global trials.