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European Heart Journal Dec 2016The efficacy and safety of different statins for human immunodeficiency virus (HIV)-positive patients in the primary prevention setting remain to be established. In the... (Comparative Study)
Comparative Study Meta-Analysis Review
The efficacy and safety of different statins for human immunodeficiency virus (HIV)-positive patients in the primary prevention setting remain to be established. In the present meta-analysis, 18 studies with 736 HIV-positive patients receiving combination antiretroviral therapy (cART) and treated with statins in the primary prevention setting were included (21.0% women, median age 44.1 years old). The primary endpoint was the effect of statin therapy on total cholesterol (TC) levels. Rosuvastatin 10 mg and atorvastatin 10 mg provided the largest reduction in TC levels [mean -1.67, 95% confidence interval (CI) (-1.99, -1.35) mmol/L; and mean -1.44, 95% CI (-1.85, -1.02) mmol/L, respectively]. Atorvastatin 80 mg and simvastatin 20 mg provided the largest reduction in low-density lipoprotein (LDL) [mean -2.10, 95% CI (-3.39, -0.81) mmol/L; and mean -1.57, 95% CI (-2.67, -0.47) mmol/L, respectively]. Pravastatin 10-20 mg [mean 0.24, 95% CI (0.10, 0.38) mmol/L] and atorvastatin 10 mg [mean 0.15, 95% CI (0.007, 0.23) mmol/L] had the largest increase in high-density lipoprotein, whereas atorvastatin 80 mg [mean -0.60, 95% CI (-1.09, -0.11) mmol/L] and simvastatin 20 mg [mean -0.61, 95% CI (-1.14, -0.08) mmol/L] had the largest reduction in triglycerides. The mean discontinuation rate was 0.12 per 100 person-years [95% CI (0.05, 0.20)], and was higher with atorvastatin 10 mg [26.5 per 100 person-years, 95% CI (-13.4, 64.7)]. Meta-regression revealed that nucleoside reverse transcriptase inhibitors-sparing regimens were associated with reduced efficacy for statin's ability to lower TC. Statin therapy significantly lowers plasma TC and LDL levels in HIV-positive patients and is associated with low rates of adverse events. Statins are effective and safe when dose-adjusted for drug-drug interactions with cART.
Topics: Adult; Anticholesteremic Agents; Atorvastatin; Cholesterol, LDL; Female; HIV Infections; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Primary Prevention; Pyrroles; Rosuvastatin Calcium; Simvastatin
PubMed: 26851703
DOI: 10.1093/eurheartj/ehv734 -
The Cochrane Database of Systematic... Jan 2016This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of dementia due to Alzheimer's disease and of vascular dementia. Some observational studies have suggested an association between statin use and lowered incidence of dementia.
OBJECTIVES
To evaluate the efficacy and safety of statins for the prevention of dementia in people at risk of dementia due to their age and to determine whether the efficacy and safety of statins for this purpose depends on cholesterol level, apolipoprotein E (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, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 11 November 2015.
SELECTION CRITERIA
We included double-blind, randomised, placebo-controlled trials in which statins were administered for at least 12 months to people at risk of dementia.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included two trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older. All participants had a history of, or risk factors for, vascular disease. The studies used different statins (simvastatin and pravastatin). Mean follow-up was 3.2 years in one study and five years in one study. The risk of bias was low. Only one study reported on the incidence of dementia (20,536 participants, 31 cases in each group; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.61 to 1.65, moderate quality evidence, downgraded due to imprecision). Both studies assessed cognitive function, but at different times using different scales, so we judged the results unsuitable for a meta-analysis. There were no differences between statin and placebo groups on five different cognitive tests (high quality evidence). Rates of treatment discontinuation due to non-fatal adverse events were less than 5% in both studies and there was no difference between statin and placebo groups in the risk of withdrawal due to adverse events (26,340 participants, 2 studies, OR 0.94, 95% CI 0.83 to 1.05).
AUTHORS' CONCLUSIONS
There is good evidence that statins given in late life to people at risk of vascular disease do not prevent cognitive decline or dementia. Biologically, it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. However, indication bias may have been a factor in these studies and the evidence from subsequent RCTs has been negative. There were limitations in the included studies involving the cognitive assessments used and the inclusion of participants at moderate to high vascular risk only.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Anticholesteremic Agents; Cognition; Dementia; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Pravastatin; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 26727124
DOI: 10.1002/14651858.CD003160.pub3 -
JACC. Cardiovascular Imaging Feb 2015Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular... (Review)
Review
Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD.
Topics: Coronary Angiography; Coronary Circulation; Diagnosis, Differential; Humans; Magnetic Resonance Imaging, Cine; Microcirculation; Microvascular Angina; Myocardial Revascularization; Positron-Emission Tomography; Practice Guidelines as Topic; Regional Blood Flow
PubMed: 25677893
DOI: 10.1016/j.jcmg.2014.12.008 -
BMC Medicine Feb 2013Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins' pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.
METHODS
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using '(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)' restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.
RESULTS
Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13).
CONCLUSIONS
Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.
Topics: Adult; Aged; Anticholesteremic Agents; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Testosterone
PubMed: 23448151
DOI: 10.1186/1741-7015-11-57 -
Journal of Atherosclerosis and... 2013To evaluate the effect of statin therapy on the decrease of common carotid artery intima-media thickness (CCA-IMT) compared to placebo or usual care. (Meta-Analysis)
Meta-Analysis
Effect of statin therapy on the progression of common carotid artery intima-media thickness: an updated systematic review and meta-analysis of randomized controlled trials.
AIM
To evaluate the effect of statin therapy on the decrease of common carotid artery intima-media thickness (CCA-IMT) compared to placebo or usual care.
METHODS
A systematic search of electronic databases (MEDLINE, EMBASE, and Cochrane Center Register) up to December 2011 was performed. Two reviewers independently determined the eligibility of randomized controlled trials (RCTs) comparing statin therapy with a placebo or usual care with a minimum follow-up of 6 months.
RESULTS
Twenty-one RCTs involving 6317 individuals were included in this review. The pooled weighted mean difference (WMD) between statin therapy and placebo or usual care on CCA-IMT was -0.029 mm (95%CI: -0.045, -0.013). Subgroup analyses showed significant effects of lovastatin (WMD: -0.077; 95%CI: -0.082, -0.073) and simvastatin (WMD: -0.069; 95%CI: -0.094, -0.045), followed by pravastatin and rosuvastatin, but no significant benefits of atorvastatin, fluvastatin, or cerivastatin. A greater decrease in mean CCA-IMT was observed in the setting of secondary prevention versus primary prevention (WMD: -0.045 vs. -0.004), in younger patients versus older patients (WMD: -0.057 vs. -0.041), and in studies where the patient proportion was males ≥ females (-0.044 vs. -0.008). Meta-regression analysis showed a significant association between changes in mean CCA-IMT with decreasing triglyceride levels. A similar, but not statistically significant trend was also found between CCA-IMT decrease and the decrease in LDL-C levels or increase in HDL-C levels.
CONCLUSION
Statin therapy is associated with a favorable decrease in CCA-IMT, an effect that seems to be mainly driven by the CCA-IMT at baseline and the extent of lipid decrease, specifically triglycerides.
Topics: Carotid Arteries; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Placebos; Randomized Controlled Trials as Topic; Tunica Intima
PubMed: 23095240
DOI: 10.5551/jat.14001 -
Clinical Cardiology Oct 2009Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. (Review)
Review
BACKGROUND
Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects.
METHODS
Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature.
RESULTS
One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not.
CONCLUSIONS
Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 19911349
DOI: 10.1002/clc.20669 -
The Cochrane Database of Systematic... Jul 2009Studies have shown that interventions which reduce total and low-density lipoprotein cholesterol levels also reduce coronary heart disease (CHD) and stroke events in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies have shown that interventions which reduce total and low-density lipoprotein cholesterol levels also reduce coronary heart disease (CHD) and stroke events in those with a history of CHD. However, it is uncertain whether treatment to alter cholesterol levels can prevent recurrence of either stroke or subsequent cardiovascular events and whether differences in outcomes exist between classes of lipid-lowering therapy. This is an update of a Cochrane review first published in 2002.
OBJECTIVES
To investigate the effect of altering serum lipids pharmacologically for preventing subsequent cardiovascular disease and stroke recurrence in patients with a history of stroke.
SEARCH STRATEGY
We searched the Cochrane Stroke Group Trials Register (last searched December 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2008), MEDLINE (1966 to December 2008) and EMBASE (1980 to December 2008). We contacted pharmaceutical companies known to produce a lipid-lowering agent for information on relevant publications or unpublished work.
SELECTION CRITERIA
Unconfounded randomised trials of participants aged 18 years and over with a history of stroke or transient ischaemic attack (TIA).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, assessed quality and extracted data.
MAIN RESULTS
We included eight studies involving approximately 10,000 participants. The active interventions were pravastatin, atorvastatin, simvastatin, clofibrate, and conjugated oestrogen. Fixed-effect analysis showed no overall effect on stroke recurrence but statin therapy alone had a marginal benefit in reducing subsequent cerebrovascular events in those with a previous history of stroke or TIA (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.77 to 1.00). There was no evidence that such intervention reduced all-cause mortality or sudden death (OR 1.00, 95% CI 0.83 to 1.20). Three statin trials showed a reduction in subsequent serious vascular events (OR 0.74, 95% CI 0.67 to 0.82).
AUTHORS' CONCLUSIONS
There is evidence that statin therapy in patients with a history of ischaemic stroke or TIA significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence. There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later. In view of this and the evidence of the benefit of statin therapy in those with a history of CHD, patients with ischaemic stroke or TIA, with or without a history of established CHD, should receive statins.
Topics: Cause of Death; Coronary Disease; Humans; Hypercholesterolemia; Hypolipidemic Agents; Ischemic Attack, Transient; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 19588332
DOI: 10.1002/14651858.CD002091.pub2 -
Health Technology Assessment... Apr 2007To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of,... (Review)
Review
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of, coronary heart disease (CHD).
DATA SOURCES
Electronic databases were searched between November 2003 and April 2004.
REVIEW METHODS
A review was undertaken to identify and evaluate all literature relating to the clinical and cost effectiveness of statins in the primary and secondary prevention of CHD and cardiovascular disease (CVD) in the UK. A Markov model was developed to explore the costs and health outcomes associated with a lifetime of statin treatment using a UK NHS perspective.
RESULTS
Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. It is hardly possible, on the evidence available from the placebo-controlled trials, to differentiate between the clinical efficacy of atorvastatin, fluvastatin, pravastatin and simvastatin. However, there is some evidence from direct comparisons between statins to suggest that atorvastatin may be more effective than pravastatin in patients with symptomatic CHD. There is limited evidence for the effectiveness of statins in different subgroups. Statins are generally considered to be well tolerated and to have a good safety profile. This view is generally supported both by the evidence of the trials included in this review and by postmarketing surveillance data. Increases in creatine kinase and myopathy have been reported, but rhabdomyolysis and hepatotoxicity are rare. However, some patients may receive lipid-lowering therapy for as long as 50 years, and long-term safety over such a timespan remains unknown. In secondary prevention of CHD, the incremental cost-effectiveness ratios (ICERs) increase with age varying between pound 10,000 and pound 17,000 per quality adjusted life year (QALY) for ages 45 and 85 respectively. Sensitivity analyses show these results are robust. In primary prevention of CHD there is substantial variation in ICERs by age and risk. The average ICERs weighted by risk range from pound 20,000 to pound 27,500 for men and from pound 21,000 to pound 57,000 for women. The results are sensitive to the cost of statins, discount rates and the modelling time frame. In the CVD analyses, which take into account the benefits of statins on reductions in stroke and TIA events, the average ICER weighted by risk level remains below pound 20,000 at CHD risk levels down to 0.5%. Limitations of the analyses include the requirement to extrapolate well beyond the timeframe of the trial period, and to extrapolate effectiveness results from higher risk primary prevention populations to the treatment of populations at much lower risk. Consequently, the results for the lower age bands and lower risks are subject to greater uncertainty and need to be treated with caution.
CONCLUSIONS
There is evidence to suggest that statin therapy is associated with a statistically significant reduction in the risk of primary and secondary cardiovascular events. As the confidence intervals for each outcome in each prevention category overlap, it is not possible to differentiate, in terms of relative risk, between the effectiveness of statins in primary and secondary prevention. However, the absolute risk of CHD death/non-fatal MI is higher, and the number needed to treat to avoid such an event is consequently lower, in secondary than in primary prevention. The generalisability of these results is limited by the exclusion, in some studies, of patients who were hypersensitive to, intolerant of, or known to be unresponsive to, statins, or who were not adequately compliant with study medication during a placebo run-in phase. Consequently, the treatment effect may be reduced when statins are used in an unselected population. The results of the economic modelling show that statin therapy in secondary prevention is likely to be considered cost-effective. In primary prevention, the cost-effectiveness ratios are dependent on the level of CHD risk and age, but the results for the CVD analyses offer support for the more aggressive treatment recommendation issued by recent guidelines in UK. Evidence on clinical endpoints for rosuvastatin is awaited from on-going trials. The potential targeting of statins at low-risk populations is however associated with major uncertainties, particularly the likely uptake and long-term compliance to lifelong medication by asymptomatic younger patients. The targeting, assessment and monitoring of low-risk patients in primary care would be a major resource implication for the NHS. These areas require further research.
Topics: Bayes Theorem; Coronary Disease; Cost-Benefit Analysis; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Meta-Analysis as Topic; Quality of Life
PubMed: 17408535
DOI: 10.3310/hta11140 -
The Journal of the American Board of... 2005Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing... (Review)
Review
Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing diabetes. Among these conditions are impaired glucose tolerance, impaired fasting glucose, obesity, gestational diabetes, hypertension, hyperlipidemia, and menopause. We here present the results of a systematic review of the literature examining the evidence for different strategies aimed at preventing type 2 diabetes in patients with these conditions. The strongest evidence supports an intensive lifestyle intervention designed to induce modest weight loss. The greatest degree of prevention, based on lesser quality evidence, may be imparted by bariatric surgery. Metformin and troglitazone have appreciable evidence in specific populations, and orlistat and acarbose have slightly less evidence among obese patients, for preventing diabetes. Ramipril, captopril, losartan, pravastatin, and estrogens show some very preliminary promise for preventing diabetes in patients treated for hypertension, hyperlipidemia, and menopause, but each needs a more rigorous evaluation. Although more questions remain to be answered, family physicians now have tools available to help our patients lead lives free of diabetes.
Topics: Bariatrics; Diabetes Mellitus, Type 2; Female; Hormone Replacement Therapy; Humans; Hyperlipidemias; Hypertension; Male; Menopause; Obesity
PubMed: 15709062
DOI: 10.3122/jabfm.18.1.37 -
BMC Family Practice Dec 2003Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol.
REVIEW METHODS
PubMed, the Cochrane Library, references lists of reports, and reviews were searched (September 2001) for randomised, double blind trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was calculated using pooled data for particular statins, and for particular doses of a statin. Pre-planned sensitivity analyses were used to determine the effects of initial concentration of total cholesterol, study duration, the effects of major trials, and effects in placebo versus active controlled trials. Information was not collected on adverse events.
RESULTS
Different statins at a range of doses reduced total cholesterol by 17-35% and LDL-cholesterol by 24-49% from baseline. Lower doses of statins generally produced less cholesterol lowering, though for most statins in trials of 12 weeks or longer there was at best only a weak relationship between dose and cholesterol reduction. Duration of treatment and baseline total cholesterol concentration did not alter the amount of the benefit attained.
CONCLUSIONS
Statins are effective medicines and confer benefit to patients in terms of primary and secondary prevention of coronary heart disease. Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and rosuvastatin 5 mg and 10 mg.
Topics: Atorvastatin; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Fatty Acids, Monounsaturated; Female; Fluorobenzenes; Fluvastatin; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Indoles; Lovastatin; Male; Pravastatin; Pyridines; Pyrimidines; Pyrroles; Randomized Controlled Trials as Topic; Rosuvastatin Calcium; Simvastatin; Sulfonamides; Triglycerides
PubMed: 14969594
DOI: 10.1186/1471-2296-4-18