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Reumatologia 2022Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing... (Review)
Review
Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.
PubMed: 35645423
DOI: 10.5114/reum.2022.114108 -
Medicine Jun 2017The high recurrent rate of chronic subdural hematoma (CSDH) has consistently confused the neurosurgeons, and the role of atorvastatin in the management of CSDH has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The high recurrent rate of chronic subdural hematoma (CSDH) has consistently confused the neurosurgeons, and the role of atorvastatin in the management of CSDH has remained unclear over past decade, and atorvastatin seems to be a safe and cost-effective treatment to CSDH. Therefore, it is necessary to conduct a systematic review to discuss the effect of atorvastatin in CSDH.
METHOD
We searched the PubMed, EMBASE, Cochrane Library, and the China Biology Medicine disc, up to March 2017, for published studies on the effects of atorvastatin in the management of CSDH, and reviewers performed a brief qualitative descriptive analysis of atorvastatin's efficacy in the management of CSDH.
RESULTS
Three eligible studies were included in this systematic review. Results indicated that atorvastatin accelerated hematoma absorption, decreased recurrence risk, and surgical requirement.
CONCLUSION
Limited evidence suggests that oral atorvastatin may be beneficial in the management of CSDH. Further high-quality studies focused on dosage, duration, hematoma size are needed to further elucidate the role of atorvastatin in the management of CSDH.
Topics: Administration, Oral; Atorvastatin; Hematoma, Subdural, Chronic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 28658127
DOI: 10.1097/MD.0000000000007290 -
TouchREVIEWS in Endocrinology Nov 2022Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by... (Review)
Review
Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.
PubMed: 36694884
DOI: 10.17925/EE.2022.18.2.96 -
British Journal of Clinical Pharmacology Aug 2022To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing... (Meta-Analysis)
Meta-Analysis Review
AIMS
To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs).
METHODS
More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness.
RESULTS
After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial).
CONCLUSION
Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Agents; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment
PubMed: 35322889
DOI: 10.1111/bcp.15331 -
Revista Medica Del Instituto Mexicano... Oct 2023Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE).
OBJECTIVE
To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events.
MATERIAL AND METHODS
A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety.
RESULTS
In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses.
CONCLUSIONS
The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.
Topics: Humans; Atorvastatin; Cardiovascular Diseases
PubMed: 37934798
DOI: 10.5281/zenodo.8319748 -
The Cochrane Database of Systematic... Jul 2014The 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... (Meta-Analysis)
Meta-Analysis Review
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.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atorvastatin; Dementia; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 25004278
DOI: 10.1002/14651858.CD007514.pub3 -
British Journal of Clinical Pharmacology May 2016The aim of this meta-analysis was to evaluate the effect of statin therapy on plasma FFA concentrations in a systematic review and meta-analysis of controlled clinical... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this meta-analysis was to evaluate the effect of statin therapy on plasma FFA concentrations in a systematic review and meta-analysis of controlled clinical trials.
METHODS
PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to February 16 2015) to identify controlled trials evaluating the impact of statins on plasma FFA concentrations. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderators.
RESULTS
Meta-analysis of data from 14 treatment arms indicated a significant reduction in plasma FFA concentrations following treatment with statins (weighted mean difference (WMD) -19.42%, 95% CI -23.19, --15.64, P < 0.001). Subgroup analysis confirmed the significance of the effect with both atorvastatin (WMD -20.56%, 95% CI -24.51, -16.61, P < 0.01) and simvastatin (WMD -18.05%, 95% CI -28.12, -7.99, P < 0.001). Changes in plasma FFA concentrations were independent of treatment duration (slope -0.10, 95% CI -0.30, 0.11, P = 0.354) and magnitude of reduction in plasma low density lipoprotein cholesterol concentrations (slope 0.55, 95% CI -0.17, 1.27, P = 0.133) by statins.
CONCLUSIONS
The results of the present study suggest that statin therapy may lower plasma FFA concentrations. The cardiovascular and metabolic significance of this finding requires further investigation.
Topics: Cardiovascular Diseases; Cholesterol, LDL; Fatty Acids, Nonesterified; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic
PubMed: 26624855
DOI: 10.1111/bcp.12854 -
The Cochrane Database of Systematic... Jan 2021Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial.
OBJECTIVES
Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work.
SELECTION CRITERIA
RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels.
AUTHORS' CONCLUSIONS
We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.
Topics: Aged; Androgens; Androstenedione; Atorvastatin; Bias; Dehydroepiandrosterone Sulfate; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Placebos; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Sex Factors; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33482034
DOI: 10.1002/14651858.CD013211.pub2 -
PloS One 2024Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to... (Meta-Analysis)
Meta-Analysis
Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI.
Topics: Humans; Atorvastatin; Percutaneous Coronary Intervention; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Treatment Outcome
PubMed: 38165842
DOI: 10.1371/journal.pone.0293404 -
The Cochrane Database of Systematic... Jun 2020Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known.
OBJECTIVES
Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins. Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions.
SELECTION CRITERIA
RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias.
MAIN RESULTS
Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects.
AUTHORS' CONCLUSIONS
Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.
Topics: Atorvastatin; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Controlled Before-After Studies; Drug Administration Schedule; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Pyridines; Quinolines; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Sex Factors; Triglycerides
PubMed: 32557581
DOI: 10.1002/14651858.CD012735.pub2