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Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.
Borovac, JA, Leth-Olsen, M, Kumric, M, D'Amario, D, Schwarz, K, Glavas, D, Bozic, J
European journal of clinical pharmacology. 2022;(1):111-126
Abstract
PURPOSE We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.
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Effects of atorvastatin on the insulin resistance in women of polycystic ovary syndrome: A systematic review and meta-analysis.
Chen, LL, Zheng, JH
Medicine. 2021;(24):e26289
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Abstract
BACKGROUND Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial. OBJECTIVE The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice. METHODS Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value. RESULTS Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD -0.06, 95% CI -0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD -1.84, 95% CI -3.06 to -0.62, P < .003). The homeostasis model assessment of insulin resistance (HOMA-IR) value showed significant decrease in the atorvastatin therapy compared to placebo (6 trials; SMD -4.12, 95% CI -6.00 to -2.23, P < .0001). In contrast to placebo, atorvastatin therapy did not decrease the BMI value significantly in PCOS patients (7 trials; SMD 0.12, 95% CI -0.07 to 0.31, P = .22). CONCLUSIONS Atorvastatin therapy can reduce insulin resistance in the treatment of patients with PCOS. In addition, further large-sample, multi-center RCTs are needed to identify these findings.
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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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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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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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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.
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Modeling Statin-Induced Reductions of Cardiovascular Events in Primary Prevention: A VOYAGER Meta-Analysis.
Karlson, BW, Nicholls, SJ, Lundman, P, Barter, PJ, Palmer, MK
Cardiology. 2018;(1):30-34
Abstract
OBJECTIVE We used individual patient data from the VOYAGER database to estimate cardiovascular (CV) risk reduction with commonly used high-intensity statins. METHODS In patients with known atherosclerotic CV disease (ASCVD) treated with high-intensity statin therapy (n = 6,735), the predicted risk reduction was estimated using the Cholesterol Treatment Trialists' Collaboration meta-analysis, which determined risk reduction per 38.7 mg/dL statin-mediated reduction in low-density lipoprotein cholesterol. RESULTS The greatest reductions in risk were seen in major vascular events (estimated rate ratios ranged from 0.55 with rosuvastatin [RSV] 40 mg to 0.60 with atorvastatin [ATV] 40 mg) and coronary heart disease death (estimated rate ratios ranged from 0.58 with RSV 40 mg to 0.64 with ATV 40 mg). CONCLUSIONS Our results show that, in individuals without clinical ASCVD, statin therapy has the potential to reduce the frequency of CV events.
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Comparing the combination therapy of ezetimibe and atorvastatin with atorvastatin monotherapy for regulating blood lipids: a systematic review and meta-analyse.
Ai, C, Zhang, S, He, Q, Shi, J
Lipids in health and disease. 2018;(1):239
Abstract
BACKGROUND Although there were many studies reporting the combination therapy of Ezetimibe and Atorvastatin's efficacy and Atorvastatin monotherapy's, the conclusions were controversial. Therefore, a systematic review and meta analysis of combination therapy and monotherapy were conducted. METHODS PubMed, Cochrane Library and Embase were searched for studies of the combination therapy of Ezetimibe and Atorvastatin and Atorvastatin monotherapy published up to October 20, 2017. Two investigators assessed the articles for eligibility and evaluated quality.The changed values and the efficacy of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Total Cholesterol (TC) and Triglyceride (TG) indicators were the outcomes. Four doses of the comparisons were included: the combination therapy of Ezetimibe (10 mg) and Atorvastatin (10 mg) (E10 + A10) versus Atorvastatin (20 mg) monotherapy (A20); E10 + A10 vs. A10; E10 + A20 vs. A40; E10 + A40 vs. A80. Review manager software 5.1 was used for quality assessment and Stata version 12.0 software was used for statistical analysis. RESULTS eventeen studies (11 publications) were included in the meta analysis. Compared with Atorvastatin monotherapy, the overall efficacy of combination therapy of Ezetimibe and Atorvastatin on lowering LDL-C (MD = - 15.38, 95% CI: -16.17 to - 14.60; I2 = 26.2%, n = 17), TC (MD = - 9.51, 95% CI: -10.28 to - 8.74; I2 = 33.7%, n = 17) and TG (MD = - 6.42, 95% CI: -7.78 to - 5.06; I2 = 0%, n = 15) and raising HDL-C (MD = 0.95, 95% CI: 0.34 to 1.57; I2 = 0%, n = 17) was significant. The efficacy of the comparison on HDL-C was largely significant for the different doses. CONCLUSIONS The overall efficacy and subgroup's efficacy of combination therapy of Ezetimibe and Atorvastatin on lowering LDL-C, TC and TG was significantly better than Atorvastatin monotherapy's. The overall and the E10 + A10/A20 group's effectiveness of combination therapy on rasing HDL-C were significantly.
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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.