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Influence of Statins on Circulating Inflammatory Cytokines in Patients With Abnormal Glucose Homeostasis: A Meta-analysis of Data From Randomized Controlled Trials.
Milajerdi, A, Sadeghi, A, Mousavi, SM, Larijani, B, Esmaillzadeh, A
Clinical therapeutics. 2020;(2):e13-e31
Abstract
PURPOSE Chronic inflammation increases the risks for cardiovascular disease, type 2 diabetes, and cancer. Recently, the antiinflammatory effects of statins, as cholesterol-lowering medications, have been considered. This study systematically reviewed and summarized earlier findings from randomized clinical trials about the effects of statins on serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6 in patients with abnormal glucose homeostasis. METHODS Relevant articles published through October 2019 were searched using suitable key words on the PubMed/MEDLINE, SCOPUS, EMBASE, and Google Scholar databases. RCTs were included if they compared the effects of statins on serum concentrations of CRP and IL-6 in adults with abnormal glucose homeostasis. The effect sizes were represented as weighted mean differences (WMDs) and 95% CI s using a random-effects model. Subgroup analysis was performed to find possible sources of heterogeneity. FINDINGS Overall, 17 publications with 21 effect sizes and which enrolled 3766 subjects (1895 participants in intervention and 1871 in control groups) were included. Combining 13 effect sizes from 10 studies, a significant reduction in serum CRP concentration following the administration of atorvastatin was found (WMD, -0.35; 95% CI, -0.54 to -0.17; I2 = 90.6%). Based on 5 effect sizes from 4 studies, we found a statistically significant reduction in serum IL-6 concentration after atorvastatin therapy (WMD, -0.44; 95% CI, -0.65 to -0.22; I2 = 93.9%). Pooling 6 effect sizes from 5 studies revealed a significantly reduced serum concentration of CRP after simvastatin therapy (WMD, -0.66; 95% CI, -0.79 to -0.54; I2 = 97.6%). IMPLICATIONS The administration of atorvastatin or simvastatin in patients with abnormal glucose hemostasis was associated with a reduced serum CRP concentration. Atorvastatin therapy might also help to decrease serum IL-6 concentration in these patients.
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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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Effect of statins on blood pressure: Analysis on adverse events released by FDA.
You, T, Liu, XG, Hou, XD, Wang, XK, Xie, HH, Ding, F, Yi, K, Zhang, P, Xie, XD
Clinical and experimental hypertension (New York, N.Y. : 1993). 2017;(4):325-329
Abstract
OBJECTIVE As a class of cholesterol-lowering drugs, statins have been reported to cause unexpected decrease in blood pressure (BP). However, most studies in this issue were subject to inadequate study design or very small sample size. The present study was designed to examine the BP-lowering effect of various statins. METHODS Here we retrieved 5.9 million clinical reports submitted to FDA Adverse Event Reporting System (FAERS) from 2004 to 2015. Meta-analysis was performed to estimate the overall reporting odds ratio (ROR) of hypotension adverse events concurrent with various statins (i.e., atorvastatin, simvastatin, and rosuvastatin). RESULTS Comparing the reporting rate of hypotension event between statins and other drugs found that atorvastatin (pooled ROR = 1.26, adjusted p-value = 8.60 × 10-4) and simvastatin (pooled ROR = 1.94, adjusted p-value = 4.16 × 10-45) were significantly associated with reduction in BP. On the other hand, the association between rosuvastatin and hypotension was observed to be nonsignificant (adjusted p-value = 0.65). CONCLUSION To our knowledge, this is the first pooled analysis on large-scale data of adverse events to identify the BP-lowering effect of statins. The results will contribute to the development of novel statin-based antihypertensive therapies. In addition, the differential effects of individual statins can warrant subsequent research on the underlying mechanisms of BP control.
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Doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in LDL-C and non-HDL-C: Results from the VOYAGER meta-analysis.
Karlson, BW, Palmer, MK, Nicholls, SJ, Lundman, P, Barter, PJ
European journal of preventive cardiology. 2016;(7):744-7
Abstract
BACKGROUND Achieving the greatest reduction in atherogenic lipoproteins requires the optimum dose and potency of statin. Using data from the VOYAGER meta-analysis, we determined doses of rosuvastatin, atorvastatin and simvastatin that induce equal reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). METHODS Least squares mean percentage change in LDL-C and non-HDL-C was calculated using 38,052 patient exposures to rosuvastatin 5-40 mg, atorvastatin 10-80 mg and simvastatin 10-80 mg. Equipotent doses were estimated by linear interpolation between actual adjacent doses. RESULTS Rosuvastatin 5 mg reduced LDL-C by 39% and non-HDL-C by 35%. Equivalent reductions in LDL-C required atorvastatin 15 mg or simvastatin 39 mg. Equivalent reductions in non-HDL-C required atorvastatin 14 mg or simvastatin 42 mg. Rosuvastatin 10 mg reduced LDL-C by 44% and non-HDL-C by 40%. Equivalent reductions in LDL-C required atorvastatin 29 mg or simvastatin 72 mg. Equivalent reductions in non-HDL-C required atorvastatin 27 mg or simvastatin 77 mg. Rosuvastatin 20 mg reduced LDL-C by 50% and non-HDL-C by 45%. Equivalent reductions in LDL-C and non-HDL-C required atorvastatin 70 mg and atorvastatin 62 mg, respectively, and were not achieved with the maximum 80 mg dose of simvastatin. Rosuvastatin 40 mg reduced LDL-C by 55% and non-HDL-C by 50%. Comparable reductions were not achieved with the maximum 80 mg doses of atorvastatin or simvastatin. CONCLUSIONS Regarding reductions in LDL-C and non-HDL-C, each rosuvastatin dose is equivalent to doses 3-3.5 times higher for atorvastatin and 7-8 times higher for simvastatin.
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Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case-Control Studies.
Hou, Q, Li, S, Li, L, Li, Y, Sun, X, Tian, H
Medicine. 2015;(37):e1268
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Abstract
Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle-Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27-3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43-3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41-10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47-5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64-5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38-6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74-2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57-3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.
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Statins for the treatment of dementia.
McGuinness, B, Craig, D, Bullock, R, Malouf, R, Passmore, P
The Cochrane database of systematic reviews. 2014;(7):CD007514
Abstract
BACKGROUND The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD. OBJECTIVES To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, ApoE genotype or cognitive level. SEARCH METHODS We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (20 January 2014). SELECTION CRITERIA Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia. DATA COLLECTION AND ANALYSIS Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD. AUTHORS' CONCLUSIONS Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.
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Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients with primary hypercholesterolemia.
Farnier, M, Guyton, JR, Jensen, E, Polis, AB, Johnson-Levonas, AO, Brudi, P
Atherosclerosis. 2013;(2):415-22
Abstract
BACKGROUND/SYNOPSIS Apolipoprotein (apo) B is highly predictive of coronary risk, especially in patients with high triglycerides (TG). This post hoc analysis evaluated the effects of lipid-lowering therapy on correlations between apoB and low-density lipoprotein cholesterol (apoB:LDL-C) and non-high-density lipoprotein cholesterol (apoB:non-HDL-C) in patients with TG< and ≥ 200 mg/dL. METHODS This analysis used data from 3 randomized clinical trials in patients with primary hypercholesterolemia receiving placebo, ezetimibe (EZE), simvastatin (SIMVA) or EZE/SIMVA for 12 weeks. Simple linear regression analyses predicted LDL-C and non-HDL-C levels corresponding to apoB values (80 mg/dL) at baseline and Week 12. RESULTS ApoB correlated with LDL-C (r ≥ 0.76) and non-HDL-C (r ≥ 0.86) at baseline. The correlations were strengthened with SIMVA and EZE/SIMVA at Week 12 (r ≥ 0.88 for LDL-C and r ≥ 0.94 for non-HDL-C). The predicted LDL-C and non-HDL-C values were lower following treatment with SIMVA or EZE/SIMVA than for placebo and EZE. For SIMVA and EZE/SIMVA, the predicted LDL-C and non-HDL-C values were closer to more aggressive LDL-C and non-HDL-C levels (i.e., 70 and 100 mg/dL, respectively). The apoB:LDL-C and apoB:non-HDL-C correlations were weaker and the predicted LDL-C values were generally lower in high TG patients than in low TG patients both at baseline and Week 12. In contrast, the predicted non-HDL-C values were generally higher in high versus low TG patients at baseline but less so at Week 12. CONCLUSION After treatment with EZE, SIMVA, or EZE/SIMVA, a given apoB value corresponds to lower LDL-C and non-HDL-C levels than those obtained from untreated patients.