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The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial.
Marlatt, KL, Steinberger, J, Rudser, KD, Dengel, DR, Sadak, KT, Lee, JL, Blaes, AH, Duprez, DA, Perkins, JL, Ross, JA, et al
Journal of adolescent and young adult oncology. 2019;(4):442-450
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Abstract
Purpose: Many adult survivors of childhood cancer are at high-risk of developing cardiovascular disease. Cancer therapy may cause damage to the vascular endothelium, thereby initiating atherosclerosis. Atorvastatin has been shown to improve endothelial function independent of reducing cholesterol, as well as reduce/slow arterial stiffness and thickening, yet has never been studied in childhood cancer survivors (CCS). Methods: Twenty-seven young adult (age 26.8 ± 6.2 years) survivors of childhood acute lymphoblastic leukemia or Non-Hodgkin's lymphoma were randomly assigned (1:1) 40 mg/day of atorvastatin or placebo for 6 months. Brachial artery flow-mediated dilation (FMD), small artery reactive hyperemia index (RHI), arterial stiffness, and carotid artery elasticity/thickness were assessed. Results: Fifteen participants completed the trial. No significant treatment effect for any vascular outcomes was observed at 6 months; however, a significant decrease in peak FMD (-3.0 [95% confidence interval [CI]: -5.3, -0.7]) and a trending significant decrease in RHI (-0.3 [95% CI: -0.62, 0.01]) was observed in the placebo group, resulting in a trend toward a treatment effects (p < 0.10). No effect on arterial stiffness, carotid arterial elasticity, or thickness was observed. Conclusion: Six months of atorvastatin treatment did not improve endothelial function or arterial stiffness in young adult CCS. While a trend toward an improvement in endothelial function was present, findings should be interpreted with caution owing to the small number of evaluable participants and subsequent lack of sufficient power. Further research in a larger sample size is needed to fully elucidate the effects of atorvastatin on vascular function. Trial registered at clinicaltrials.gov as NCT01733953.
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Prophylactic atorvastatin prior to intra-arterial administration of iodinated contrast media for prevention of contrast-induced acute kidney injury: A meta-analysis of randomized trial data
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Sun, YY, Liu, LY, Sun, T, Wu, MY, Ma, FZ
Clinical nephrology. 2019;(3):123-130
Abstract
BACKGROUND The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. OBJECTIVE This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. MATERIALS AND METHODS Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. RESULTS A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35 - 0.62, p < 0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25 - 0.66, p = 0.0003) and the placebo group (OR 0.50, 95% CI 0.26 - 0.98, p = 0.04). CONCLUSION Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.
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CONTROL: A randomized phase 2 study of obeticholic acid and atorvastatin on lipoproteins in nonalcoholic steatohepatitis patients.
Pockros, PJ, Fuchs, M, Freilich, B, Schiff, E, Kohli, A, Lawitz, EJ, Hellstern, PA, Owens-Grillo, J, Van Biene, C, Shringarpure, R, et al
Liver international : official journal of the International Association for the Study of the Liver. 2019;(11):2082-2093
Abstract
BACKGROUND & AIMS Nonalcoholic steatohepatitis (NASH) is a chronic and severe form of nonalcoholic fatty liver disease that can progress to cirrhosis and hepatocellular carcinoma and is a risk factor for cardiovascular disease. Although NASH has no approved treatments, obeticholic acid (OCA), a synthetic bile acid and farnesoid X receptor (FXR) agonist, was shown to improve histological features of NASH and fibrosis. Considering that FXR activation influences plasma lipoprotein concentrations, the Combination OCA aNd sTatins for monitoRing Of Lipids (CONTROL) study evaluated how statins can regulate lipoprotein metabolism with OCA treatment in patients with NASH. METHODS This randomized, double-blind, placebo-controlled, phase 2 study began with a 5-week screening/statin washout; 84 patients with NASH were randomly assigned (1:1:1:1) to receive placebo or 5 mg, 10 mg or 25 mg OCA once daily during the 16-week double-blind phase. Concurrent once daily atorvastatin (10 mg/days) was initiated at Week 4 with subsequent titration. Enrolled patients had biopsy-confirmed diagnosis of NASH with no evidence of hepatic decompensation. Plasma was collected to analyse lipoprotein parameters. RESULTS At Week 4, all OCA groups had an increase from baseline in mean low-density lipoprotein cholesterol (LDLc) and mean LDL particle concentration (LDLpc), mostly owing to large, less atherogenic LDLc particles. Atorvastatin 10 mg decreased LDLc and LDLpc levels below baseline in all OCA groups by Week 8; higher doses did not provide additional clinical benefits. CONCLUSIONS The CONTROL study showed that OCA-induced increases in LDLc in patients with NASH were mitigated with atorvastatin. The combination of OCA and atorvastatin was generally safe and well tolerated (NCT02633956).
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Low Baseline High-Sensitive C-Reactive Protein is Associated with Coronary Atherosclerosis Regression: Insights from the MILLION Study.
Sakata, K, Gamou, T, Tada, H, Hayashi, K, Ino, H, Yamagishi, M, , , ,
Journal of atherosclerosis and thrombosis. 2019;(5):442-451
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Abstract
AIM: The prospective, randomized, multicenter Myocardial Ischemia Treated with Percutaneous Coronary Intervention and Plaque Regression by Lipid Lowering & Blood Pressure Controlling assessed by Intravascular Ultrasonography (MILLION) study demonstrated that combined treatment with atorvastatin and amlodipine enhanced coronary artery plaque regression. Although the baseline high-sensitive C-reactive protein (hs-CRP) reportedly plays an important role in atherogenesis, few data exist regarding the relationship between hs-CRP and plaque regression in patients receiving a combined atorvastatin and amlodipine therapy. METHODS A total of 68 patients (male, 55; mean age, 64.2 years) with baseline and follow-up 3-dimensional intravascular ultrasound examinations in the MILLION study were stratified by baseline hs-CRP level quartiles. The serial measurements of lipid, blood pressure, and percentage changes in the plaque volume were compared between the groups, and the factors associated with the percentage change in the plaque volume were assessed. RESULTS There were no significant between-group differences in the extent of change in low-density lipoprotein cholesterol (LDL-C) or systolic and diastolic blood pressure after 18-24 months of treatment. The percentage change in the plaque volume showed a linear association with the baseline hs-CRP (p for trend <0.05); however, there was no correlation with changes in LDL-C or systolic and diastolic blood pressure. In the multiple regression analysis, the baseline hs-CRP level was independently associated with the percentage change in the plaque volume (β=0.29, p=0.022). CONCLUSIONS Coronary plaque regression was associated with the baseline hs-CRP level in patients treated with a combined lipid- and blood pressure-lowering therapy.
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Comparative effects of atorvastatin 80 mg and rosuvastatin 40 mg on the levels of serum endocan, chemerin, and galectin-3 in patients with acute myocardial infarction.
Tunçez, A, Altunkeser, BB, Öztürk, B, Ateş, MS, Tezcan, H, Aydoğan, C, Kırık, EC, Yalçın, U, Aygül, N, Demir, K, et al
Anatolian journal of cardiology. 2019;(5):240-249
Abstract
OBJECTIVE Endocan, chemerin, and galectin-3 are discrete biomarkers associated with cardiovascular diseases and acting through different pathophysiological pathways. The aim of this study is to investigate and compare the effects of high doses of atorvastatin and rosuvastatin on serum endocan, chemerin, and galectin-3 levels in patients with acute myocardial infarction (AMI). METHODS Sixty-three patients with AMI were randomized to receive atorvastatin (80 mg/day) or rosuvastatin (40 mg/day) after percutaneous revascularization. Serum levels of endocan, chemerin, and galectin-3 were evaluated at baseline and after 4-week therapy. RESULTS Endocan levels were not decreased statistically significantly with atorvastatin 80 mg, but rosuvastatin 40 mg markedly decreased the levels of endocan according to baseline [from 110.27 (86.03-143.69) pg/mL to 99.22 (78.30-122.87) pg/mL with atorvastatin 80 mg and from 110.73 (77.28-165.22) pg/mL to 93.40 (70.48-115.13) pg/mL with rosuvastatin 40 mg, p=0.242 for atorvastatin 80 mg and p=0.014 for rosuvastatin 40 mg]. Chemerin levels significantly decreased in both groups according to baseline [from 264.90 (196.00-525.95) ng/mL to 135.00 (105.95-225.65) ng/mL with atorvastatin 80 mg and from 309.95 (168.87-701.27) ng/mL to 121.25 (86.60-212.65) ng/mL with rosuvastatin 40 mg, p<0.001, respectively, for both groups]. Galectin-3 levels did not change markedly with atorvastatin 80 mg, but they decreased with rosuvastatin 40 mg [from 17.00 (13.10-22.25) ng/mL to 19.30 (15.25-23.45) ng/mL with atorvastatin 80 mg, p=0.721, and from 18.25 (12.82-23.82) ng/mL to 16.60 (10.60-20.15) ng/mL with rosuvastatin 40 mg, p=0.074]. There were no significant between-group differences in terms of absolute and percentage changes of endocan, chemerin, and galectin-3 at 4 weeks. CONCLUSION We reported that both statins similarly decreased the endocan levels, whereas rosuvastatin seems to have more prominent effects on the reduction of the chemerin and galectin-3 levels in patients with AMI.
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Comparison of the effect of 80 vs 40 mg atorvastatin in patients with isolated coronary artery bypass graft surgery: A randomized clinical trial.
Shekari, A, Forouzannia, SK, Davarpasand, T, Talasaz, AH, Jalali, A, Gorabi, AM, Lotfi-Tokaldany, M, Bagheri, J
Journal of cardiac surgery. 2019;(8):670-675
Abstract
OBJECTIVES Atorvastatin can decrease cardiac injury after coronary artery bypass graft (CABG) surgery. We compared the effects of 80 and 40 mg of atorvastatin per day on the levels of cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) after an isolated CABG. METHODS This randomized single-blind parallel clinical trial enrolled 125 patients (mean age = 60.59 ± 8.37 years) who were candidates for elective isolated CABG at the Tehran Heart Center between May 2017 and December 2017. Patients were randomly allocated into two groups to receive either 80 mg (n = 62) or 40 mg of atorvastatin (n = 63) per day, 5 days before surgery. The levels of cTnT and CK-MB, used as myocardial injury markers, were measured at baseline and then at 8 and 24 hours after CABG. RESULTS The levels of CK-MB and cTnT at baseline and at 8 and 24 hours following CABG were not significantly different between the two groups. Our repeated measures analysis of variance showed that the levels of CK-MB and cTnT increased significantly over time (P < .001). No significant interaction was observed between time and the atorvastatin dosage on the levels of either CK-MB (P = .159) or cTnT (P = .646). In addition, the between-group effects were not significant for CK-MB (P = .632) and cTnT (P = .126). CONCLUSION The higher dose of atorvastatin (80 mg) did not exert a more protective effect than the standard dose of atorvastatin (40 mg) after CABG surgery.
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Effects of short-term atorvastatin use in patients with calcium stones: A randomized placebo-controlled clinical trial.
Taheri, F, Taheri, M, Basiri, A, Khoshdel, A, Samadian, F, Tavasoli, S
Investigative and clinical urology. 2019;(6):472-479
Abstract
PURPOSE A few experimental and observational studies have reported that atorvastatin prevents calcium oxalate stone formation. Our study is the first to investigate the effect of atorvastatin on 24-hour urinary metabolites, urinary malondialdehyde (U-MDA) (an oxidative stress marker) and urinary neutrophil gelatinase-associated lipocalin (U-NGAL) (a renal tubular injury marker) in patients with calcium stones and hyperoxaluria. MATERIALS AND METHODS This randomized, double-blind, placebo-controlled, parallel-group clinical trial included 32 adults with recurrent calcium stone formation and hyperoxaluria. All participants received a 3-month course of either atorvastatin (20 mg/d) or placebo of an identical shape. Both groups received the usual nutritional care based on the European Association of Urology guidelines. RESULTS Twenty-eight participants completed the study. Serum levels of total and low-density lipoprotein cholesterol decreased in the atorvastatin group, and these changes were significantly different between groups (p<0.001). No statistically significant differences were observed between intergroup changes of the 24-hour urinary metabolite analysis, the U-MDA to creatinine ratio and the U-NGAL to creatinine ratio. CONCLUSIONS Atorvastatin administration at a dose of 20 mg/d for 3 months did not affect 24-hour urinary metabolite, U-MDA and U-NGAL levels in recurrent calcium stone formers. However, this study could not disprove the preventive role of atorvastatin in kidney stone formation. Future studies should consider a larger sample size, longer follow-up, different drug doses, and measurements of multiple biomarkers of oxidative stress and tubular injury.
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Statins influence biomarkers of low grade inflammation in apparently healthy people or patients with chronic diseases: A systematic review and meta-analysis of randomized clinical trials.
Milajerdi, A, Larijani, B, Esmaillzadeh, A
Cytokine. 2019;:154752
Abstract
BACKGROUND No earlier study summarized findings on the effect of statins on inflammatory biomarkers in apparently healthy individuals or those with chronic diseases. This study was done to systematically review earlier publications on the effect of statins on serum concentrations of C-reactive protein (CRP) and Interleukin-6 (IL-6) in apparently healthy individuals or those with chronic diseases. METHODS We searched relevant publications published up to December 2018 in PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar databases. For this purpose, suitable MESH and non-MESH keywords were used. Randomized placebo-controlled clinical trials that examined the effect of statins on serum concentrations of CRP and IL-6 in apparently healthy adults or those with chronic diseases were included. RESULTS Overall, 18 studies with 23 effect sizes, that enrolled 32,156 individuals (38% female and 62% male; mean age: 44.79 years) were included. When we combined 21 effect sizes from 16 studies, we observed a significant reduction in circulating levels of CRP following administration of statins [Weighted Mean Difference (WMD): -0.80; 95% CI: -1.05, -0.56]. Combining 12 effect sizes from 11 studies, a significant reduction was found in serum CRP concentrations following administration of Atorvastatin (WMD: -0.57; 95% CI: -0.78, -0.35). Pooling 5 effect sizes from 2 studies, we found a significant reduction in serum concentrations of CRP following administration of Simvastatin (WMD: -0.29; 95% CI: -0.49, -0.10; I2 = 88.5%). Combining 6 effect sizes from 5 studies, we found a significant reduction in serum IL-6 concentrations after Atorvastatin therapy (WMD: -2.13; 95% CI: -3.96, -0.30; I2 = 98.6%). CONCLUSIONS In conclusion, we found that statins administration in apparently healthy people or those with chronic diseases help reducing serum CRP concentrations. In addition, Atorvastatin administration resulted in reduced serum IL-6 concentrations in these people.
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Treatment with Free Triple Combination Therapy of Atorvastatin, Perindopril, Amlodipine in Hypertensive Patients: A Real-World Population Study in Italy.
Perrone, V, Veronesi, C, Gambera, M, Nati, G, Perone, F, Tagliabue, PF, Degli Esposti, L, Volpe, M
High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension. 2019;(5):399-404
Abstract
INTRODUCTION Polytherapy is often required to treat the comorbidity of hypertension and hyperlipidemia. Fixed-dose co-formulation, rather than free combinations, simplifies medication taking and also improves adherence to medication, which is the key for a successful management of these conditions. AIM: To determine the number of patients potentially eligible for treatment with triple fixed-dose atorvastatin/perindopril/amlodipine (CTAPA), and to estimate if an unmet medical need exists among CTAPA free combination treated patients. METHODS This observational retrospective study was based on administrative databases of 3 Italian Local Health Units. The cohort comprised adult patients with at least one prescription of amlodipine and perindopril (either as free combination or co-formulated) and atorvastatin during 2014. Follow-up period started on the date of prescription of the 3 molecules (index date) and lasted 1 year. Adherence to CTAPA was analyzed during follow-up, by using the proportion of days covered (PDC). RESULTS 2292 patients (9.1 per 10,000 beneficiaries) had a prescription for CTAPA as free combination. Only 1249 (54.5%) were adherent to the therapy (PDC ≥ 80%); among them, a small percentage required dosage modification. The number of patients with CTAPA increased during the study period. Discontinuation of drugs prescribed the year before interested 582 patients in 2014, and 522 in 2015. Considering the Italian national population (n = 60,782,668), it was estimated that 69,542 hypertensive patients could be eligible for fixed-dose CTAPA during 2014. CONCLUSIONS Real-world analysis among patients with free combination therapy can be applied to estimate the eligible population for fixed combination, and to evaluate the appropriateness of their prescriptions. Moreover, fixed-dose CTAPA could effectively improve adherence, which was calculated to be low in the free combination cohort.
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Should we add atorvastatin to irbesartan for improving renoprotective effects in early diabetic nephropathy? A meta-analysis of randomized controlled trials.
Zuo, Y, Li, T, Lei, Z
Pharmacological research. 2019;:104286
Abstract
Angiotensin II receptor blocker has exhibited their renal protective benefits in diabetic nephropathy. This meta-analysis aimed to evaluate the effects of adding atorvastatin to irbesartan in early diabetic nephropathy. A systematic literature search was performed in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang database until March 25, 2019. Randomized controlled trials evaluating the effects of adding atorvastatin to irbesartan in early diabetic nephropathy were eligible. Primary endpoint was urinary albumin excretion rate, serum creatinine, and blood urea nitrogen. Serum level of total cholesterol, triglyceride, fasting blood glucose, interleukin-6,and C-reactive protein (CRP) as well as blood pressure were secondary endpoints. Seventeen trials involving 1,390 patients were identified. Compared with irbesartan alone, co-administration of atorvastatin and irbesartan significantly reduced urinary albumin excretion rate (weighted mean differences [WMD] -21.22 μg/min; 95% confidence interval [CI] -26.95 to -15.50), serum creatinine (WMD -6.46 μmol/L; 95%CI -8.52 to 4.39),BUN (WMD -0.46 mmol/L; 95%CI -0.64 to -0.27), total cholesterol (WMD -1.79 mmol/L; 95%CI -2.34 to -1.23), triglyceride (WMD -0.93 mmol/L; 95%CI -1.20 to -0.67),and systolic blood pressure (WMD -2.27 mmHg; 95%CI -4.01 to -0.53), CRP (standard mean difference [SMD] 1.57; 95%CI -2.24 to -0.9), and Interleukin-6 (SMD 1.53; 95%CI -2.29 to -0.78). However, there was a significantly increased risk of nausea/vomiting (risk ratio 3.15; 95% CI 1.18-8.38) on the co-administration group. In conclusion, adding atorvastatin to irbesartan achieves additional renal protective benefits in early diabetic nephropathy patients. However, these findings should be interpreted with caution due to suboptimal methodological quality of the analyzed trials.