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Short-term rosuvastatin treatment for the prevention of contrast-induced acute kidney injury in patients receiving moderate or high volumes of contrast media: a sub-analysis of the TRACK-D study.
Zhang, J, Li, Y, Tao, GZ, Chen, YD, Hu, TH, Cao, XB, Jing, QM, Wang, XZ, Ma, YY, Wang, G, et al
Chinese medical journal. 2015;(6):784-9
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Abstract
BACKGROUND Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown. METHODS In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200-300 ml, n = 712) or (high contrast volume [HCV], ≥ 300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days. RESULTS Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273). CONCLUSIONS Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.
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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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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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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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Effect of rosuvastatin therapy on troponin I release following percutaneous coronary intervention in nonemergency patients (from the TIP 3 study).
Veselka, J, Hájek, P, Tomašov, P, Tesař, D, Brůhová, H, Matějovič, M, Branny, M, Studenčan, M, Zemánek, D
The American journal of cardiology. 2014;(3):446-51
Abstract
Several randomized studies have suggested that pretreatment with statins may reduce a periprocedural biomarker release in patients who underwent percutaneous coronary intervention (PCI); however, results remain controversial. The purpose of this study was to investigate the effect of a 1-day rosuvastatin therapy on troponin I release in patients who underwent nonemergency PCI. A total of 445 patients with angina pectoris were randomly assigned to therapy with rosuvastatin (20 mg 12 hours before coronary angiography + 20 mg immediately before PCI; rosuvastatin group, 220 patients) or PCI without statin therapy (control group, 225 patients). In patients taking statins (73%), rosuvastatin was added to their long-term statin therapy. The primary end point was the incidence of TnI microleak defined as TnI elevation >1.5× upper limit of normal, and the secondary end point was the incidence of post-PCI TnI elevation >3× upper limit of normal. The incidence of primary and secondary end point in the rosuvastatin versus control group was 13.6% versus 12% (p = 0.61) and 8.2% versus 7.1% (p = 0.67), respectively. Patients with C-reactive protein ≥2.0 mg/L had a decreased release of post-PCI TnI in the rosuvastatin group (0.032 [0.010 to 0.143] μg/L vs 0.056 [0.018 to 0.241] μg/L; p = 0.04). In conclusion, 1-day rosuvastatin therapy (20 mg twice a day) did not influence post-PCI TnI release in patients with angina. However, these results suggest that, in patients with an advanced inflammatory status, rosuvastatin loading therapy might have a cardioprotective effect.
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Prognostic effect of high-sensitive troponin T assessment in elderly patients with chronic heart failure: results from the CORONA trial.
Gravning, J, Askevold, ET, Nymo, SH, Ueland, T, Wikstrand, J, McMurray, JJ, Aukrust, P, Gullestad, L, Kjekshus, J, ,
Circulation. Heart failure. 2014;(1):96-103
Abstract
BACKGROUND The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study. METHODS AND RESULTS Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (≥60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality. CONCLUSIONS Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
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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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Fatigue as a predictor of outcome in patients with heart failure: analysis of CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).
Perez-Moreno, AC, Jhund, PS, Macdonald, MR, Petrie, MC, Cleland, JG, Böhm, M, van Veldhuisen, DJ, Gullestad, L, Wikstrand, J, Kjekshus, J, et al
JACC. Heart failure. 2014;(2):187-97
Abstract
OBJECTIVES The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF) ≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. BACKGROUND Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis. METHODS At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0 = none, 1 = heavy exertion, 2 = moderate exertion, 3 = slight exertion, 4 = rest); a 4-point scale was used for dyspnea (1 to 4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n = 535), fatigue score 2 (n = 1,632), and fatigue score 3 to 4 (n = 1,663); and a dyspnea score of 1 (n = 292), dyspnea score of 2 (n = 1,695), and dyspnea score of 3 to 4 (n = 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality. RESULTS In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n = 810], vs. group 1, 30% [n = 160]; dyspnea: group 3, 50% [n = 918], vs. group 1, 28% [n = 82]) and all-cause mortality (fatigue: group 3, 38% [n = 623], vs. group 1, 24% [n = 130]; dyspnea: group 3, 38% [n = 697], vs. group 1, 23% [n = 66], log-rank p < 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes. CONCLUSIONS In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment.
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Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction - a pilot study.
Chitose, T, Sugiyama, S, Sakamoto, K, Shimomura, H, Yamashita, T, Hokamaki, J, Tsunoda, R, Shiraishi, S, Yamashita, Y, Ogawa, H
Atherosclerosis. 2014;(1):251-8
Abstract
OBJECTIVE Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI). METHODS Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)]. RESULTS Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01). CONCLUSION Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with increasing CoQ10/LDL-C. CLINICAL TRIAL REGISTRATION URL http://www.umin.ac.jp/ctr/index.htm Unique Identifier: UMIN000003893.
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Thyroid-stimulating hormone and clinical outcomes: the CORONA trial (controlled rosuvastatin multinational study in heart failure).
Perez, AC, Jhund, PS, Stott, DJ, Gullestad, L, Cleland, JG, van Veldhuisen, DJ, Wikstrand, J, Kjekshus, J, McMurray, JJ
JACC. Heart failure. 2014;(1):35-40
Abstract
OBJECTIVES This study sought to examine the association between thyroid status and clinical outcomes in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. BACKGROUND Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). METHODS In CORONA, 4,987 patients underwent baseline thyroid-stimulating hormone (TSH) measurement, 237 of which (4.8%) were receiving thyroid replacement therapy (TRT). Patients were classified as euthyroid (TSH: 0.3 to 5.0 μU/ml, and no TRT), hyperthyroid (<0.3 μU/ml and no TRT), or hypothyroid (>5.0 μU/ml and no TRT). The outcome composites of cardiovascular (CV) death or hospitalization for heart failure (HF), the components of this composite, and all-cause death were compared among hyperthyroid, hypothyroid, and euthyroid states, using multivariable models adjusting for previously reported prognostic variables. RESULTS A total of 91.3% of patients were euthyroid, 5.0% were hypothyroid, and 3.7% were hyperthyroid. Compared with euthyroid patients, hypothyroid patients were more likely to have a history of stroke, had worse renal function and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, were more likely to be treated with an antiarrhythmic drug (or have an implantable cardioverter defibrillator), and were less likely to smoke or be treated with a beta-blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. In univariate analyses, hypothyroidism was associated with an increased risk of the composite outcome of CV death or HF hospitalization (hazard ratio: 1.29; 95% confidence interval: 1.07 to 1.57; p = 0.008), as well as all-cause death (HR: 1.36; 95% confidence interval: 1.03 to 1.76; p = 0.004). However, after adjustment for other known predictors of outcome, the associations were weakened, and when NT-proBNP was added to the models, the association between hypothyroidism and all outcomes was eliminated. CONCLUSIONS Thyroid status is not an independent predictor of outcome in heart failure with reduced ejection fraction. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310).