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Lipid-lowering efficacy of atorvastatin.
Adams, SP, Tsang, M, Wright, JM
The Cochrane database of systematic reviews. 2015;(3):CD008226
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Abstract
BACKGROUND This represents the first update of this review, which was published in 2012. Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids. OBJECTIVES Primary objective To quantify the effects of various doses of atorvastatin on serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides in individuals with and without evidence of cardiovascular disease. The primary focus of this review was determination of the mean per cent change from baseline of LDL-cholesterol. Secondary objectives • To quantify the variability of effects of various doses of atorvastatin.• To quantify withdrawals due to adverse effects (WDAEs) in placebo-controlled randomised controlled trials (RCTs). SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2013), MEDLINE (1966 to December Week 2 2013), EMBASE (1980 to December Week 2 2013), Web of Science (1899 to December Week 2 2013) and BIOSIS Previews (1969 to December Week 2 2013). We applied no language restrictions. SELECTION CRITERIA Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of three to 12 weeks. DATA COLLECTION AND ANALYSIS Two review authors independently assessed eligibility criteria for studies to be included and extracted data. We collected information on withdrawals due to adverse effects from placebo-controlled trials. MAIN RESULTS In this update, we found an additional 42 trials and added them to the original 254 studies. The update consists of 296 trials that evaluated dose-related efficacy of atorvastatin in 38,817 participants. Included are 242 before-and-after trials and 54 placebo-controlled RCTs. Log dose-response data from both trial designs revealed linear dose-related effects on blood total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The Summary of findings table 1 documents the effect of atorvastatin on LDL-cholesterol over the dose range of 10 to 80 mg/d, which is the range for which this systematic review acquired the greatest quantity of data. Over this range, blood LDL-cholesterol is decreased by 37.1% to 51.7% (Summary of findings table 1). The slope of dose-related effects on cholesterol and LDL-cholesterol was similar for atorvastatin and rosuvastatin, but rosuvastatin is about three-fold more potent. Subgroup analyses suggested that the atorvastatin effect was greater in females than in males and was greater in non-familial than in familial hypercholesterolaemia. Risk of bias for the outcome of withdrawals due to adverse effects (WDAEs) was high, but the mostly unclear risk of bias was judged unlikely to affect lipid measurements. Withdrawals due to adverse effects were not statistically significantly different between atorvastatin and placebo groups in these short-term trials (risk ratio 0.98, 95% confidence interval 0.68 to 1.40). AUTHORS' CONCLUSIONS This update resulted in no change to the main conclusions of the review but significantly increases the strength of the evidence. Studies show that atorvastatin decreases blood total cholesterol and LDL-cholesterol in a linear dose-related manner over the commonly prescribed dose range. New findings include that atorvastatin is more than three-fold less potent than rosuvastatin, and that the cholesterol-lowering effects of atorvastatin are greater in females than in males and greater in non-familial than in familial hypercholesterolaemia. This review update does not provide a good estimate of the incidence of harms associated with atorvastatin because included trials were of short duration and adverse effects were not reported in 37% of placebo-controlled trials.
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HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass.
Lewicki, M, Ng, I, Schneider, AG
The Cochrane database of systematic reviews. 2015;(3):CD010480
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Abstract
BACKGROUND Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased mortality. Statin drugs can produce more than one effect independent of their lipid lowering effect, and may improve kidney injury through inhibition of postoperative inflammatory responses. OBJECTIVES This review aimed to look at the evidence supporting the benefits of perioperative statins for AKI prevention in hospitalised adults after surgery who require cardiac bypass. The main objectives were to 1) determine whether use of statins was associated with preventing AKI development; 2) determine whether use of statins was associated with reductions in in-hospital mortality; 3) determine whether use of statins was associated with reduced need for RRT; and 4) determine any adverse effects associated with the use of statins. SEARCH METHODS We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared administration of statin therapy with placebo or standard clinical care in adult patients undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were eligible for inclusion. All forms and dosages of statins in conjunction with any duration of pre-operative therapy were considered for inclusion in this review. DATA COLLECTION AND ANALYSIS All authors extracted data independently and assessments were cross-checked by a second author. Likewise, assessment of study risk of bias was initially conducted by one author and then by a second author to ensure accuracy. Disagreements were arbitrated among authors until consensus was reached. Authors from two of the included studies provided additional data surrounding post-operative SCr as well as need for RRT. Meta-analyses were used to assess the outcomes of AKI, SCr and mortality rate. Data for the outcomes of RRT and adverse effects were not pooled. Adverse effects taken into account were those reported by the authors of included studies. MAIN RESULTS We included seven studies (662 participants) in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, pre-operative statin treatment was not associated with a reduction in postoperative AKI, need for RRT, or mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to -11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin group compared to placebo. AUTHORS' CONCLUSIONS Analysis of currently available data did not suggest that preoperative statin use is associated with decreased incidence of AKI in adults after surgery who required cardiac bypass. Although a significant reduction in SCr was seen postoperatively in people treated with statins, this result was driven by results from a single study, where SCr was considered as a secondary outcome. The results of the meta-analysis should be interpreted with caution; few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Large high quality RCTs are required to establish the safety and efficacy of statins to prevent AKI after cardiac surgery.
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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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A meta-analysis of randomized head-to-head trials for effects of rosuvastatin versus atorvastatin on apolipoprotein profiles.
Takagi, H, Umemoto, T, ,
The American journal of cardiology. 2014;(2):292-301
Abstract
To determine which statin will better improve the apolipoprotein (Apo) profiles (ApoA-I levels, ApoB levels, and ApoB/A-I ratios), we performed a meta-analysis of randomized head-to-head trials of rosuvastatin versus atorvastatin therapy. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2012 using Web-based search engines (PubMed and OVID). The search terms included "apolipoprotein," "rosuvastatin," "atorvastatin," "randomized," "randomly," and "randomization." Of 42 potentially relevant studies initially screened, 25 reports of randomized trials enrolling 14,283 patients were included. A pooled analysis for the percentage of changes in ApoA-I demonstrated a benefit of rosuvastatin versus atorvastatin in the comparison of all rosuvastatin/atorvastatin dose ratios (mean difference 2.97%, 3.39%, 5.77%, and 6.25%). For the percentage of changes in ApoB, a benefit was seen for rosuvastatin versus atorvastatin in the 1/1 (-6.06%) and 1/2 dose ratio (-1.80%). However, a benefit was seen for atorvastatin versus rosuvastatin in the 1/4 (2.38%) and 1/8 dose ratio (6.59%). The pooled analysis for the percentage of changes in the Apo B/A-I ratios demonstrated a benefit for rosuvastatin versus atorvastatin in the 1/1 (-7.22%) and 1/2 dose ratio (-3.51%), with no difference in the 1/4 dose ratio. In contrast, a benefit was seen for atorvastatin versus rosuvastatin in the 1/8 dose ratio (4.03%). In conclusion, rosuvastatin might increase Apo A-I levels at all dose ratios and decrease ApoB levels and ApoB/A-I ratios in the 1/1 and 1/2 dose ratio versus atorvastatin. Only higher dose atorvastatin appeared to be more effective for the reduction in ApoB levels (1/4 and 1/8 dose ratio) and Apo B/A-I ratios (1/8 dose ratio).