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Current Medical Research and Opinion Dec 2015To assess the efficacy of fenofibrate and statin dual therapy versus a double or equivalent dose of statin monotherapy. (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To assess the efficacy of fenofibrate and statin dual therapy versus a double or equivalent dose of statin monotherapy.
METHODS
A systematic literature search and meta-analysis was performed for publications before 1 January 2014 in MEDLINE, Embase, and BIOSIS Previews, among others.
RESULTS
The difference in percentage change from baseline was in favor of dual therapy versus a double dose of statin monotherapy for triglycerides (difference -20%; standard error [SE] 2.6%) and HDL-C (8.7%; SE 1.2%), but not for LDL-C (8.4%; SE 1.5%), non-HDL-C (2.8%; SE 1.1%), total cholesterol (4.5%; SE 1.0%) and apolipoprotein B (2.6%; SE 1.1%). For high intensity statins, the difference in percentage change from baseline was in favor of dual therapy versus equivalent statin monotherapy for triglycerides (-17%; SE 2.6%) and for HDL-C (8.7%; SE 1.9%). The difference in percentage change from baseline for LDL-C was 6% (SE 1.7%), implying a greater reduction in LDL-C with statin monotherapy. For moderate intensity statins, the difference in percentage change from baseline was in favor of dual therapy versus equivalent statin monotherapy for triglycerides (-24.2%; SE 1.2%) and HDL-C (8.2%; SE 0.9%). LDL-C decreased 2.2% (SE 1.4%) more with dual therapy.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
When aiming to change HDL-C or triglycerides, dual therapy is to be preferred to doubling the statin dose; conversely, doubling the statin dose is to be preferred when aiming to reduce LDL-C. If the aim is both to change HDL-C or triglycerides and to reduce LDL-C, the importance of the three outcomes may need to be weighed depending on the intensity of the statin. Combining high intensity statin therapy with fenofibrate improves the effect on HDL-C and triglycerides, but lowers the effect on LDL-C. Combining a moderate intensity statin with fenofibrate improves the effect on HDL-C and triglycerides without reducing the effect on LDL-C. There is a need for long-term randomized clinical trials to compare dual therapy versus doubling the statin dose to assess the importance of improvement in HDL-C and triglycerides versus improvement in LDL-C in terms of cardiovascular outcomes. Further, the addition of ezetimibe to statin/fenofibrate therapy may be of interest.
Topics: Apolipoproteins B; Cholesterol; Drug Therapy, Combination; Fenofibrate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 26397380
DOI: 10.1185/03007995.2015.1098597 -
Journal of the American Heart... Sep 2015Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Debate over the role of fructose in mediating cardiovascular risk remains active. To update the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease (low-density lipoprotein cholesterol [LDL]-C, apolipoprotein B, non-high-density lipoprotein cholesterol [HDL-C]), and metabolic syndrome (triglycerides and HDL-C), we conducted a systematic review and meta-analysis of controlled feeding trials.
METHODS AND RESULTS
MEDLINE, EMBASE, CINHAL, and the Cochrane Library were searched through July 7, 2015 for controlled feeding trials with follow-up ≥7 days, which investigated the effect of oral fructose compared to a control carbohydrate on lipids (LDL-C, apolipoprotein B, non-HDL-C, triglycerides, and HDL-C) in participants of all health backgrounds. Two independent reviewers extracted relevant data. Data were pooled using random effects models and expressed as mean difference with 95% CI. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). Eligibility criteria were met by 51 isocaloric trials (n=943), in which fructose was provided in isocaloric exchange for other carbohydrates, and 8 hypercaloric trials (n=125), in which fructose supplemented control diets with excess calories compared to the control diets alone without the excess calories. Fructose had no effect on LDL-C, non-HDL-C, apolipoprotein B, triglycerides, or HDL-C in isocaloric trials. However, in hypercaloric trials, fructose increased apolipoprotein B (n=2 trials; mean difference = 0.18 mmol/L; 95% CI: 0.05, 0.30; P=0.005) and triglycerides (n=8 trials; mean difference = 0.26 mmol/L; 95% CI: 0.11, 0.41; P<0.001). The study is limited by small sample sizes, limited follow-up, and low quality scores of the included trials.
CONCLUSIONS
Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories (+21% to 35% energy). When isocalorically exchanged for other carbohydrates, fructose had no adverse effects on blood lipids. More trials that are larger, longer, and higher quality are required.
CLINICAL TRIALS REGISTRATION
URL: https://www.clinicaltrials.gov/. Unique Identifier: NCT01363791.
Topics: Apolipoprotein B-100; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Cholesterol, HDL; Cholesterol, LDL; Controlled Clinical Trials as Topic; Dietary Carbohydrates; Dyslipidemias; Energy Intake; Fructose; Humans; Lipids; Metabolic Syndrome; Risk Factors; Time Factors; Triglycerides
PubMed: 26358358
DOI: 10.1161/JAHA.114.001700 -
The British Journal of Nutrition Aug 2015The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total... (Meta-Analysis)
Meta-Analysis Review
The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95% CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0.97 (95% CI 0.94, 1.00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0.86 (95% CI 0.69, 1.09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47%, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0.94 (95% CI 0.89, 0.99), seven studies, I2= 78%; highest v. lowest HR 0.82 (95% CI 0.66, 1.02), nine studies, I2= 81%) and HDL-C (dose-response HR 0.81 (95% CI 0.65, 1.02), five studies, I2= 30 %; highest v. lowest HR 0.82 (95% CI 0.69, 0.98), five studies, I2= 0%). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.
Topics: Apolipoprotein A-I; Apolipoproteins B; Biomarkers, Tumor; Breast Neoplasms; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Prospective Studies; Risk Factors
PubMed: 26173770
DOI: 10.1017/S000711451500183X -
Experimental and Clinical Endocrinology... Apr 2013Carnitine is an endogenous metabolite and exogenous nutrient with a pivotal role in lipid metabolism. Plasma levels of carnitine are reduced in type 2 Diabetes Mellitus... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Carnitine is an endogenous metabolite and exogenous nutrient with a pivotal role in lipid metabolism. Plasma levels of carnitine are reduced in type 2 Diabetes Mellitus (T2DM). The aim was to evaluate the metabolic effects of the administration of L-carnitine in T2DM.
METHOD
A systematic review was performed. Relevant randomized, controlled-trials trials were searched in Pubmed, Trip Database and Cochrane Library, and selected when they had enough methodological quality assessed with the Jadad scale. Article search strategy included "Carnitine" OR "L-carnitine" AND "Diabetes -Mellitus" OR "Diabetes mellitus, type 2" OR "Noninsulindependent-diabetes mellitus". Meta-analysis was performed, and the difference of means calculated with a 95% confidence interval. Heterogeneity was evaluated with the Q statistic.
RESULTS
The systematic review included 4 trials with 284 patients. Oral L-carnitine lowered fasting plasma glucose [-14.3 mg/dl (CI95% - 23.2 to -5.4); p=0,002], total cholesterol [-7.8 mg/dL (95%CI -15.5 to -0.1); p=0.09], low density lipoprotein [-8.8 mg/dl (CI95% -12.2 to -8.5), p<0.0001], apolipoprotein-B100 [-7.6 mg/dl (CI95% -13.6 to -1.6); p=0.013] and apolipoprotein-A1 [-6.0 mg/dl (CI95% -10.5 a -1.5); p=0.523]. There was no significant heterogeneity. The changes in triglycerides, lipoprotein (a) or HbA(1c) were not significant.
CONCLUSION
The administration of L-carnitine in type 2 diabetes mellitus is associated with an improvement in glycaemia and plasma lipids.
Topics: Apolipoprotein A-I; Apolipoprotein B-100; Blood Glucose; Carnitine; Cholesterol; Diabetes Mellitus, Type 2; Fasting; Humans; Insulin; Lipids; Lipoproteins, LDL; MEDLINE; Postprandial Period; Randomized Controlled Trials as Topic
PubMed: 23430574
DOI: 10.1055/s-0033-1333688 -
Atherosclerosis Nov 2012Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III... (Review)
Review
BACKGROUND
Lipoprotein association phospholipase A2 (Lp-PLA(2)), an enzyme which has been found in atherosclerotic plaque is currently under investigation in large Phase III clinical trials of vascular disease prevention. We assessed in a variety of different population settings variation of Lp-PLA(2) mass and activity across gender, ethnicity, diabetes, kidney disease and metabolic syndrome. We also assessed correlations with measures of circulating lipids, systemic inflammation and adiposity.
METHODS
Systematic review of studies measuring Lp-PLA(2) and at least one of the relevant characteristics in >50 participants.
RESULTS
We identified a total of 77 studies involving 102,499 participants meeting the inclusion criteria. Lp-PLA(2) mass and activity were consistently approximately 10% higher in males than females and 15% higher in Caucasians than African Americans or Hispanics. There were no clear associations of Lp-PLA(2) mass or activity with type II diabetes, markers of systemic inflammation (C-reactive protein, fibrinogen) or with body mass index. Correlations of Lp-PLA(2) mass or activity with low density lipoprotein cholesterol and apolipoprotein B were moderate and positive, whilst correlations with high density lipoprotein cholesterol were negative and moderate to weak. There was no clear differences in associations with any of the above characteristics in groups defined based upon prevalent cardiovascular disease or its risk factors.
CONCLUSIONS
Despite considerable variability in absolute levels of Lp-PLA(2) across studies, the variability of Lp-PLA(2) across gender, ethnicity, and levels of circulating lipids and markers of systemic inflammation are more consistent and appear not to vary importantly across categories defined by CVD or its risk factors.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Black or African American; Animals; Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Inflammation; Lipids; Male; Risk Factors; Sex Factors; White People
PubMed: 22784637
DOI: 10.1016/j.atherosclerosis.2012.06.020 -
Current Medicinal Chemistry 2009Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for... (Review)
Review
Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of dyslipidemia on postprandial lipemia. Statins, beyond their effects on fasting lipid levels, reduce also postprandial lipemia mainly by inhibiting the production of apoB containing lipoproteins from the liver and thus increasing the clearance of triglyceride-rich lipoproteins of either liver or intestinal origin. Fibrates decrease fasting triglyceride and increase high density lipoprotein cholesterol levels. Besides, fibrates are particularly potent drugs in the reduction of postprandial lipemia; they decrease the production or triglyceride-rich lipoproteins and increase their clearance by enhancing the activity of lipoprotein lipase.
Topics: Apolipoproteins B; Cholesterol Ester Transfer Proteins; Chylomicrons; Clofibric Acid; Coronary Artery Disease; Dyslipidemias; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Postprandial Period; Triglycerides
PubMed: 19149572
DOI: 10.2174/092986709787002763