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Mayo Clinic Proceedings. Innovations,... Jun 2019To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
OBJECTIVE
To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia.
PATIENTS AND METHODS
We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration.
RESULTS
Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; <.001). Atorvastatin showed the highest odds (OR 2.66; 95% CI, 1.74-4.06; <.001) followed by rosuvastatin (OR 1.35; 95% CI, 1.06-1.70; =.01) and lovastatin (OR 1.53; 95% CI, 1.03-2.28; =.04). Pravastatin, fluvastatin, and simvastatin yielded no statistically different odds compared with placebo.
CONCLUSIONS
A dose-dependent risk of developing hypertransaminasemia occurs in patients taking atorvastatin, rosuvastatin, and lovastatin.
PubMed: 31193835
DOI: 10.1016/j.mayocpiqo.2019.01.003 -
Drug Design, Development and Therapy 2019Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pravastatin has been suggested to increase circulating adiponectin in humans. However, results of randomized controlled trials (RCTs) are inconsistent. We aimed to systematically evaluate the influence of pravastatin on circulating adiponectin in humans by performing a meta-analysis of RCTs.
MATERIALS AND METHODS
Studies were identified via systematic searching of PubMed, Embase, and Cochrane's Library databases. A random effect model was used to pool the results. Meta-regression and subgroup analyses were applied to explore the source of heterogeneity.
RESULTS
Eight RCTs with nine comparisons of 595 participants were included. Pravastatin treatment was associated with a significant increased level of circulating adiponectin as compared with controls (weighted mean difference [WMD] =0.63 µg/mL; 95% CI, 0.17-1.09 µg/mL; =0.007) with moderate heterogeneity (I2=28%). These results were confirmed by meta-analysis of double-blinded placebo-controlled RCTs (WMD =0.82 µg/mL; =0.01). Meta-regression analyses indicated that proportions of males in each study were positively correlated with the effect of pravastatin on adiponectin (coefficient: 0.015, =0.03). Subgroup analyses confirmed that pravastatin significantly increased adiponectin in studies of males (WMD =1.41 µg/mL; =0.008), but not in those of females (WMD =-0.04 µg/mL; =0.94).
CONCLUSION
Pravastatin treatment is associated with increased circulating adiponectin. Gender difference may exist regarding the effect of pravastatin treatment on adiponectin.
Topics: Adiponectin; Cardiovascular Diseases; Humans; Pravastatin; Randomized Controlled Trials as Topic
PubMed: 31190742
DOI: 10.2147/DDDT.S186992 -
Hellenic Journal of Cardiology : HJC =... 2019Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of...
BACKGROUND
Observational studies have suggested that statins might reduce postoperative atrial fibrillation (AF) in patients undergoing cardiac surgery. However, a number of retrospective studies have shown equivocal results. We aimed to evaluate whether different statins can reduce the risk for AF at different doses.
METHODS
We searched PubMed, EMBASE, and the Cochrane Database for all published randomized controlled trials (RCTs) that examined the effects of statin therapy on AF up to June 2016. A random-effects model was used when there was substantial heterogeneity.
RESULTS
Eighteen published studies that included 4003 statin-naive patients (2009 receiving satins and 1994 receiving regime) with sinus rhythm before cardiac surgeries were identified for inclusion in the analysis. Thirteen studies investigated the prevention of AF by atorvastatin, two studies investigated the prevention of AF by rosuvastatin, two studies investigated the prevention of AF by simvastatin, and one study investigated the prevention of AF by pravastatin. The remaining two studies compared the effects of different doses of atorvastatin on the prevention of AF in patients undergoing coronary artery bypass grafting (CABG). Overall, statin therapy was associated with a significant decrease in the risk for AF (relative risk [RR]: 0.57, 95% confidence interval [CI]: 0.45-0.73, P = 0.000). However, subgroup analyses showed that only atorvastatin reduced the risk for new-onset AF in patients after cardiac surgery (RR: 0.53, 95% CI: 0.41-0.69, P = 0.000). Patients undergoing CABG possibly received more benefits from statin therapy (RR: 0.52, 95% CI: 0.39-0.68).Statin therapy in a moderate dose may be optimal (RR: 0.42, 95% CI: 0.28-0.64).
CONCLUSIONS
This meta-analysis suggests that statin therapy has an overall protective effect against postoperative AF, among which atorvastatin in a moderate dose was significantly associated with a decreased risk for new-onset AF in patients after CABG. Moreover, simvastatin may also exert a significant protective effect against the AF recurrences in patients undergoing cardiac surgeries; hence, further prospective studies are warranted.
Topics: Atorvastatin; Atrial Fibrillation; Cardiac Surgical Procedures; Dose-Response Relationship, Drug; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Postoperative Complications; Prognosis
PubMed: 29307691
DOI: 10.1016/j.hjc.2017.12.012 -
Journal of the American College of... Aug 2017High-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-sensitivity assays can quantify cardiac troponins I and T (hs-cTnI, hs-cTnT) in individuals with no clinically manifest myocardial injury.
OBJECTIVES
The goal of this study was to assess associations of cardiac troponin concentration with cardiovascular disease (CVD) outcomes in primary prevention studies.
METHODS
A search was conducted of PubMed, Web of Science, and EMBASE for prospective studies published up to September 2016, reporting on associations of cardiac troponin concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were extracted by 2 independent reviewers, supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random effects meta-analysis.
RESULTS
A total of 28 relevant studies were identified involving 154,052 participants. Cardiac troponin was detectable in 80.0% (hs-cTnI: 82.6%; hs-cTnT: 69.7%). In PROSPER, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 1.43 (95% confidence interval [CI]: 1.31 to 1.56) for CVD (11,763 events), 1.67 (95% CI: 1.50 to 1.86) for fatal CVD (7,775 events), 1.59 (95% CI: 1.38 to 1.83) for CHD (7,061 events), and 1.35 (95% CI: 1.23 to 1.48) for stroke (2,526 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027).
CONCLUSIONS
In the general population, high cardiac troponin concentration within the normal range is associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.
Topics: Biomarkers; Cardiovascular Diseases; Global Health; Humans; Incidence; Risk Assessment; Troponin
PubMed: 28750699
DOI: 10.1016/j.jacc.2017.05.062 -
The Cochrane Database of Systematic... Jul 2017Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.
OBJECTIVES
To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.
SEARCH METHODS
Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017.
SELECTION CRITERIA
Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion and extracted data.
MAIN RESULTS
We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence).
AUTHORS' CONCLUSIONS
Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Brachial Artery; Carotid Intima-Media Thickness; Child; Child, Preschool; Cholesterol, LDL; Creatine Kinase; Female; Heterozygote; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Puberty; Randomized Controlled Trials as Topic; Vasodilation
PubMed: 28685504
DOI: 10.1002/14651858.CD006401.pub4 -
Asian Journal of Andrology 2017The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A... (Meta-Analysis)
Meta-Analysis Review
The aim of this study is to investigate the effect of statins type or even when grouping statins by hydrophilic or hydrophobic nature on prostate cancer risk. A literature search was performed without language restrictions using the databases of PubMed (1984.1-2015.3), MEDLINE (1984.1-2015.3), and EMBASE (1990.1-2015.3). Two independent reviewers appraised eligible studies and extracted data. Weighted averages were reported as relative risk (RR) with 95% confidence intervals (CI). Statistic heterogeneity scores were assessed with the standard Cochran's Q-test and I2 statistic. Publication bias was detected using the Begg's and Egger's tests. All statistical analyses were conducted by STATA version 10. Finally, fourteen studies were included in the meta-analysis. Both hydrophilic and hydrophobic statins showed no association with incidence of prostate cancer (RR = 1.00, 95% CI: 0.82-1.17; RR = 0.90, 95% CI: 0.73-1.08, respectively). Meanwhile, the risk of prostate cancer was not reduced in simvastatin (RR = 0.89, 95% CI: 0.72-1.05), pravastatin (RR = 1.02, 95% CI: 0.94-1.11), atorvastatin (RR = 0.89, 95% CI: 0.76-1.02), fluvastatin (RR = 0.99, 95% CI: 0.97-1.01), or lovastatin users (RR = 0.94, 95% CI: 0.79-1.08). The funnel plot showed that there was no publication bias. The results showed that statins had a neutral effect on prostate cancer risk; hydrophilic and hydrophobic statins as well as any subtype of statins did not affect the risk of prostate cancer.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Male; Prostatic Neoplasms; Risk
PubMed: 27924788
DOI: 10.4103/1008-682X.190327 -
The Cochrane Database of Systematic... Nov 2016Elevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Elevated levels of total cholesterol and low-density lipoprotein play an important role in the development of atheromas and, therefore, in cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and is principally produced at night (between 12:00 am and 6:00 am). The adjustment of hypolipaemic therapy to biologic rhythms is known as chronotherapy. Chronotherapy is based on the idea that medication can have different effects depending on the hour at which it is taken. Statins are one of the most widely used drugs for the prevention of cardiovascular events. In usual clinical practice, statins are administered once per day without specifying the time when they should be taken. It is unknown whether the timing of statin administration is important for clinical outcomes.
OBJECTIVES
To critically evaluate and analyse the evidence available from randomised controlled trials regarding the effects of chronotherapy on the effectiveness and safety of treating hyperlipidaemia with statins.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science Conference Proceedings, and various other resources including clinical trials registers up to November 2015. We also searched the reference lists of relevant reviews for eligible studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), enrolling people with primary or secondary hyperlipidaemia. To be included, trials must have compared any chronotherapeutic lipid-lowering regimen with statins and any other statin lipid-lowering regimen not based on chronotherapy. We considered any type and dosage of statin as eligible, as long as the control and experimental arms differed only in the timing of the administration of the same statin. Quasi-randomised studies were excluded.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We extracted the key data from studies in relation to participants, interventions, and outcomes for safety and efficacy. We calculated odds ratios (OR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Using the GRADE approach, we assessed the quality of the evidence and we used the GRADEpro Guideline Development Tool to import data from Review Manager to create 'Summary of findings' tables.
MAIN RESULTS
This review includes eight RCTs (767 participants analysed in morning and evening arms). The trials used different lipid-lowering regimens with statins (lovastatin: two trials; simvastatin: three trials; fluvastatin: two trials; pravastatin: one trial). All trials compared the effects between morning and evening statin administration. Trial length ranged from four to 14 weeks. We found a high risk of bias in the domain of selective reporting in three trials and in the domain of incomplete outcome data in one trial of the eight trials included. None of the studies included were judged to be at low risk of bias.None of the included RCTs reported data on cardiovascular mortality, cardiovascular morbidity, incidence of cardiovascular events, or deaths from any cause. Pooled results showed no evidence of a difference in total cholesterol (MD 4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow-up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C) (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9 weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510 participants, five trials, mean follow-up 9 weeks, low-quality evidence) between morning and evening statin administration.With regard to safety outcomes, five trials (556 participants) reported adverse events. Pooled analysis found no differences in statins adverse events between morning and evening intake (OR 0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks, low-quality evidence).
AUTHORS' CONCLUSIONS
Limited and low-quality evidence suggested that there were no differences between chronomodulated treatment with statins in people with hyperlipidaemia as compared to conventional treatment with statins, in terms of clinically relevant outcomes. Studies were short term and therefore did not report on our primary outcomes, cardiovascular clinical events or death. The review did not find differences in adverse events associated with statins between both regimens. Taking statins in the evening does not have an effect on the improvement of lipid levels with respect to morning administration. Further high-quality trials with longer-term follow-up are needed to confirm the results of this review.
Topics: Anticholesteremic Agents; Drug Chronotherapy; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hyperlipidemias; Indoles; Lovastatin; Pravastatin; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 27888640
DOI: 10.1002/14651858.CD009462.pub2 -
Atherosclerosis Oct 2016The effect of statin therapy on plasma adiponectin levels has not been conclusively studied. Therefore, we aimed to evaluate this effect through a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The effect of statin therapy on plasma adiponectin levels has not been conclusively studied. Therefore, we aimed to evaluate this effect through a systematic review and meta-analysis of available randomized controlled trials (RCTs).
METHODS
Quantitative data synthesis was performed using a random-effects model with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics.
RESULTS
In 30 studies (43 study arms) with 2953 participants, a significant increase in plasma adiponectin levels was observed after statin therapy (WMD: 0.57 μg/mL, 95% CI: 0.18, 0.95, p = 0.004). In subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and pitavastatin were found to change plasma adiponectin concentrations by 0.70 μg/mL (95% CI: -0.26, 1.65), 0.50 μg/mL (95% CI: -0.44, 1.45), -0.70 μg/mL (95% CI: -1.08, -0.33), 0.62 μg/mL (95% CI: -0.12, 1.35), and 0.51 μg/mL (95% CI: 0.30, 0.72), respectively. With respect to duration of treatment, there was a significant increase in the subset of trials lasting ≥12 weeks (WMD: 0.88 μg/mL, 95% CI: 0.19, 1.57, p = 0.012) but not in the subset of <12 weeks of duration (WMD: 0.18 μg/mL, 95% CI: -0.23, 0.58, p = 0.390). Random-effects meta-regression suggested a significant association between statin-induced elevation of plasma adiponectin and changes in plasma low density lipoprotein cholesterol levels (slope: 0.04; 95% CI: 0.01, 0.06; p = 0.002).
CONCLUSIONS
The meta-analysis showed a significant increase in plasma adiponectin levels following statin therapy. Although statins are known to increase the risk for new onset diabetes mellitus, our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression.
Topics: Adiponectin; Adult; Aged; Atorvastatin; Cardiovascular Diseases; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Pravastatin; Quinolines; Randomized Controlled Trials as Topic; Regression Analysis; Rosuvastatin Calcium; Simvastatin
PubMed: 27498397
DOI: 10.1016/j.atherosclerosis.2016.07.897 -
Oncotarget Apr 2016Usage of statins is suggested to decrease the incidence of HCC. When it comes to different statin subtypes, the chemopreventive action remains controversial. We aim to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Usage of statins is suggested to decrease the incidence of HCC. When it comes to different statin subtypes, the chemopreventive action remains controversial. We aim to compare the usage of different statins and reduction of HCC risk.
METHODS
We searched PubMed, Embase.com and Cochrane Library database up to August 10, 2015. Duplicated or overlapping reports were eliminated. We performed a traditional pair-wise meta-analysis and a Bayesian network meta-analysis to compare different treatments with a random-effects model.
RESULTS
We reviewed five observational studies enrolling a total of 87127 patients who received at least two different treatment strategies including rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, cerivastatin, and lovastatin or observation alone. Direct comparisons showed that usage of atorvastatin (OR 0.63, 95%CI 0.45-0.89) and fluvastatin (OR 0.58, 95%CI 0.40-0.85) could significantly cut the risk of liver cancer. The difference of indirect comparisons between the included regimens is not statistically significant. However, usage of all types of statins, such as fluvastatin (RR 0.55, 95%CI 0.26-1.11), atorvastatin (RR 0.59, 95%CI 0.30-1.16), simvastatin (RR 0.69, 95%CI 0.38-1.25), cerivastatin (RR 0.71, 95%CI 0.19-2.70), pravastatin (RR 0.72, 95%CI 0.37-1.45), lovastatin (RR 0.81, 95%CI 0.34-1.96) and rosuvastatin (RR 0.92, 95%CI 0.44-1.80), appeared to be superior to observation alone. Notably, fluvastatin was hierarchically the best when compared with the six other statins.
CONCLUSIONS
Our analyses indicate the superiority of usage of statins in reduction of liver cancer. Available evidence supports that fluvastatin is the most effective strategy for reducing HCC risk compared with other statin interventions.
Topics: Atorvastatin; Bayes Theorem; Carcinoma, Hepatocellular; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Liver; Liver Neoplasms; Lovastatin; Observational Studies as Topic; Pravastatin; Pyridines; Rosuvastatin Calcium; Simvastatin; Treatment Outcome
PubMed: 26943041
DOI: 10.18632/oncotarget.7832