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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