나이아신 (HDL)

AIM: Lipoprotein(a) (Lp(a)) is a proatherogenic and prothrombotic lipoprotein. Our aim was to quantify the extended-release nicotinic acid Lp(a) reducing effect with a meta-analysis of the available randomized clinical trials. METHODS: A meta-analysis and random-effects meta-regression were performed on data pooled from 14 randomized placebo-controlled clinical trials published between 1998 and 2015, comprising 17 treatment arms, which included 9013 subjects, with 5362 in the niacin arm. RESULTS: The impact of ER niacin on plasma Lp(a) concentrations was reported in 17 treatment arms. Meta-analysis suggested a significant reduction of Lp(a) levels following ER niacin treatment (weighted mean difference - WMD: -22.90%, 95% CI: -27.32, -18.48, p<0.001). Results also remained similar when the meta-analysis was repeated with standardized mean difference as summary statistic (WMD: -0.66, 95% CI: -0.82, -0.50, p<0.001). When the studies were categorized according to the administered dose, there was a comparable effect between the subsets of studies with administered doses of <2000mg/day (WMD: -21.85%, 95% CI: -30.61, -13.10, p<0.001) and ≥2000mg/day (WMD: -23.21%, 95% CI: -28.41, -18.01, p<0.001). The results of the random-effects meta-regression did not suggest any significant association between the changes in plasma concentrations of Lp(a) with dose (slope: -0.0001; 95% CI: -0.01, 0.01; p=0.983), treatment duration (slope: -0.40; 95% CI: -0.97, 0.17; p=0.166), and percentage change in plasma HDL-C concentrations (slope: 0.44; 95% CI: -0.48, 1.36; p=0.350). CONCLUSION: In this meta-analysis of randomized placebo-controlled clinical trials, treatment with nicotinic acid was associated with a significant reduction in Lp(a) levels.

BACKGROUND AND AIM: High density lipoproteins (HDL) have been addressed as a potential strategy for cardiovascular prevention, with great controversies on pharmacological approaches for HDL-elevation. Our aim was to compare HDL-rising treatment with niacin or CETP-inhibitors with optimal medical therapy in cardiovascular outcome. METHODS AND RESULTS: Randomized trials were searched. Primary endpoint was cardiovascular death, secondary were: non fatal myocardial infarction; coronary revascularization; cerebrovascular accidents and safety endpoints. As many as 18 randomized trials, for a total of 69,515 patients, were included. HDL-modifiers did not reduce cardiovascular mortality (2.3%vs3.4%; OR [95%CI] = 0.96 [0.87-1.05], p = 0.37, phet = 0.58), with no benefit from niacin/CETP inhibitors according to patients' risk profile (beta [95%CI] = -0.14 [-0.29 to 0.02], p = 0.09) or the amount of HDL increase (beta [95%CI] = 0.014 [-0.008 to 0.04], p = 0.21). Niacin but not CETP-I reduced myocardial infarction and coronary revascularization, but higher rate of SAE occurred with HDL-modifiers (OR [95%CI] = 1.24 [1.18-1.31], p < 0.00001, phet = 0.02), in particular new onset of diabetes with niacin and worsening of hypertension with CETP-inhibitors. CONCLUSIONS: Niacin and CETP inhibitors do not influence cardiovascular mortality. Significant benefits in MI and coronary revascularization were observed with niacin, despite the higher occurrence of diabetes.

Emerging evidence suggests that personalized dietary supplement regimens can significantly influence lipid metabolism and cardiovascular risk. The efficacy of AI-guided dietary supplement prescriptions, compared with standard physician-guided prescriptions, remains underexplored. In a randomized, parallel-group pilot study, 70 patients aged 40-75 years with LDL-C levels between 70 and 190 mg/dL were enrolled. Participants were randomized to receive either AI-guided dietary supplement prescriptions or standard physician-guided prescriptions for 90 days. The primary endpoint was the percent change in LDL-C levels. Secondary endpoints included changes in total cholesterol, HDL-C, triglycerides, and hsCRP. Supplement adherence and side effects were monitored. Sixty-seven participants completed the study. The AI-guided group experienced a 25.3% reduction in LDL-C levels (95% CI: -28.7% to -21.9%), significantly greater than the 15.2% reduction in the physician-guided group (95% CI: -18.5% to -11.9%; p < 0.01). Total cholesterol decreased by 15.4% (95% CI: -19.1% to -11.7%) in the AI-guided group compared with 8.1% (95% CI: -11.5% to -4.7%) in the physician-guided group (p < 0.05). Triglycerides were reduced by 22.1% (95% CI: -27.2% to -17.0%) in the AI-guided group versus 12.3% (95% CI: -16.7% to -7.9%) in the physician-guided group (p < 0.01). HDL-C and hsCRP changes were not significantly different between groups. The AI-guided group received a broader variety of supplements, including plant sterols, omega-3 fatty acids, red yeast rice, coenzyme Q10, niacin, and fiber supplements. Side effects were minimal and comparable between groups. AI-guided dietary supplement prescriptions significantly reduce LDL-C and triglycerides more effectively than standard physician-guided prescriptions, highlighting the potential for AI-driven personalization in managing hypercholesterolemia.

HDL-apolipoprotein A-I exchange (HAE) measures a functional property associated with HDL's ability to mediate reverse cholesterol transport. HAE has been used to examine HDL function in case-control studies but not in studies of therapeutics that alter HDL particle composition. This study investigates whether niacin and omega-3 fatty acids induce measurable changes in HAE using a cohort of fifty-six subjects with metabolic syndrome (MetS) who were previously recruited to a double-blind trial where they were randomized to 16 weeks of treatment with dual placebo, extended-release niacin (ERN, 2g/day), prescription omega-3 ethyl esters (P-OM3, 4g/day), or the combination. HAE was assessed at the beginning and end of the study. Compared to placebo, ERN and P-OM3 alone significantly increased HAE by 15.1% [8.2, 22.0] (P<0.0001) and 11.1% [4.5, 17.7] (P<0.0005), respectively, while in combination they increased HAE by 10.0% [2.5, 15.8] (P = 0.005). When HAE was evaluated per unit mass of apoA-I ERN increased apoA-I specific exchange activity by 20% (2, 41 CI, P = 0.02) and P-OM3 by 28% (9.6, 48 CI, P<0.0006). However the combination had no statistically significant effect, 10% (-9, 31 CI, P = 0.39). With regard to P-OM3 therapy in particular, the HAE assay detected an increase in this property in the absence of a concomitant rise in HDL-C and apoA-I levels, suggesting that the assay can detect functional changes in HDL that occur in the absence of traditional biomarkers. Copyright: © 2024 Borja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH sho

BACKGROUND: Hyperlipidemia, a major pathological condition associated with disrupted lipid levels and physiological redox homeostasis. The excessive release of reactive oxygen species (ROS) leads to enhanced lipid peroxidation, aggravated atherosclerosis and oxidative stress. Integration of natural antioxidant blends in alone or with conventional treatments can alleviate these issues synergistically contributing least side effects. Published literature reported the efficacy of natural antioxidants as individual and in combinations in various conditions but less data is available on their evaluation in low dose ratio blends particularly in hypercholesterolemic diet. METHODS: Antihyperlipidemic effects of selected natural antioxidants; the phenolic oligomeric proanthocyanidins (OPC) and pterostilbene (PT) with niacin (NA) were investigated in current study. Their effects on lipid profile, lipid peroxidation and their aptitude to establish redox state between oxidants and antioxidants in body were evaluated in high cholesterol diet fed animal model. Male albino rabbits (n = 6) weighing 1.2-1.6 kg, supplemented with high cholesterol diet (400 mg/kg) for 12 weeks were used in the experiment. Antioxidants were administered individual high (100 mg/kg) and in low dose combinations (total dose = 100 mg/kg). Student's t test and one way analysis of variance (ANOVA) followed by Dunnet's test were used as statistical tools for evaluation. RESULTS: The results showed synergistic effects of low dose antioxidant blends. Therapies retarded elevation in blood lipid levels, lipid peroxidation and blood antioxidant depletion and consequently contributed in reestablishing redox homeostasis. The LDL/HDL ratio and atherogenic index were suppressed significantly in blend therapies with maximum effects of 59.3 and 25 % (p >0.001) observed in 50:30:20 ratios of OPC, NA and PT, compared to individual therapies 37 and 18 % max respectively. Moreover the results were also in close proximity with the statin therapy (52.66, 26.28 %). CONCLUSION: This study provides an evidence for natural antioxidants blends superiority over individual therapy in chronic diseases like hyperlipidemia. Such th

BACKGROUND: The degree of glycemic control in patients with type 2 diabetes mellitus (T2DM) may alter lipid levels and may alter the efficacy of lipid-modifying agents. OBJECTIVE: Evaluate the lipid-modifying efficacy of extended-release niacin/laropiprant (ERN/LRPT) in subgroups of patients with T2DM with better or poorer glycemic control. METHODS: Post hoc analysis of clinical trial data from patients with T2DM who were randomized 4:3 to double-blind ERN/LRPT or placebo (n=796), examining the lipid-modifying effects of ERN/LRPT in patients with glycosylated hemoglobin or fasting plasma glucose levels above and below median baseline levels. RESULTS: At Week 12 of treatment, ERN/LRPT significantly improved low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a), compared with placebo, with equal efficacy in patients above or below median baseline glycemic control. Compared with placebo, over 36 weeks of treatment more patients treated with ERN/LRPT had worsening of their diabetes and required intensification of antihyperglycemic medication, irrespective of baseline glycemic control. Incidences of other adverse experiences were generally low in all treatment groups. CONCLUSION: The lipid-modifying effects of ERN/LRPT are independent of the degree of baseline glycemic control in patients with T2DM (NCT00485758).

25. Johns Hopkins Med Lett Health After 50. 2011 Dec;23(10):1-2. Combining niacin with statins: does it help heart health? [No authors listed]

26. Curr Opin Lipidol. 2010 Apr;21(2):161-2. doi: 10.1097/MOL.0b013e32833768ea. Hyperlipidaemia and cardiovascular disease: low HDL-cholesterol as a therapeutic target in statin-treated patients: a role for nicotinic acid (niacin)? Choudhury RP.

27. Med Lett Drugs Ther. 2008 Apr 7;50(1283):25-6. Simcor: a niacin/simvastatin combination. [No authors listed]

Combination of statins with niacin appears to be an attractive association, in the presence of mixed dyslipidemia with low HDL-c levels, when monotherapy is insufficient to achieve target lipid levels. Clinical benefits were observed by the combination of statins with niacin in the FATS, HATS and ARBITER 2 trials, showing attenuation of atherosclerosis development and/or reduction in coronary events following favorable lipid changes. In general, this combination can be well-tolerated. Recommendations for appropriate monitoring of liver and muscle enzymes are important to reduce the rate of side effects. In addition, careful titration of each drug is recommended.

Current pharmacological regimens for hypertriglyceridemia and low high-density lipoprotein (HDL) are limited to the peroxisome proliferator-activated receptor (PPAR) alpha activating fibrates, niacin, and statins. This pilot study examined the impact of simultaneous stimulation of cyclic adenosine monophosphate with a beta-adrenergic agonist and PPARgamma with pioglitazone (PIO) on lipoprotein composition in moderately obese, healthy subjects. Subjects were treated with PIO (45 mg) to stimulate PPARgamma or a combination of ephedrine (25 mg TID), a beta-agonist, with caffeine (200 mg TID), a phosphodiesterase inhibitor (ephedrine plus caffeine), or both for 16 weeks. Lipoproteins were separated by gradient ultracentrifugation into very low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein (LDL), and 3 HDL (L, M, and D) subfractions. Apolipoproteins were measured by high-performance liquid chromatography. PIO alone reduced the core triglyceride (TG) content relative to cholesterol ester (CE) in VLDL (-40%), IDL (-25%), and HDL-M (-38%). Ephedrine plus caffeine alone reduced LDL CE (-13%), phospholipids (-9%), and apolipoprotein (apo) B (-13%); increased HDL-M LpA-I (HDL containing apoA-I without apoA-II, 28%), CE/TG (23%), and CE/apoA-I (8%) while reducing apoA-II (-10%); and increased HDL-L LpA-I (29%). Combination therapy reduced total plasma TG (-28%), LDL cholesterol (LDL-C, -10%), apoB (-16%), apoB/apoA-I ratio (-21%) while increasing HDL cholesterol (HDL-C, 21%), total plasma apoA-I (12%), LpA-I (43%), and apoC-I (26%). It also reduced VLDL total mass (-34%) and apoC-III (-39%), LDL CE (-13%), apoB (-13%), and total mass (-11%). Combination therapy increased HDL-L CE/TG (32%), apoC-I (30%), apoA-I (56%), and LpA-I (70%), as well as HDL-M CE (35%), phospholipids (24%), total mass (19%), apoC-I (25%), apoA-I (18%), and LpA-I (56%). In conclusion, simultaneous beta-adrenergic and PPARgamma activation produced beneficial effects on VLDL, LDL, HDL-L, and HDL-M. Perhaps the most important impact of combination therapy was dramatic increases in LpA-I and apoC-I in HDL-L and HDL-M, which were much greater than the sum of the mono

The use of niacin, alone and in combination, for the treatment of dyslipidemia in patients with or at risk for coronary heart disease (CHD), is discussed. Cardiovascular risk is independently predicted not only by high levels of low-density lipoprotein cholesterol (LDL-C), but also low levels of high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides. Moreover, we now understand that LDL particle size and number are associated with differing levels of atherogenicity. Metabolic syndrome, increasingly being recognized as a marker for elevated cardiovascular risk, is associated with atherogenic dyslipidemia characterized by low HDL-C, high triglycerides, and small, dense LDL particles. Controlled clinical studies have shown that niacin therapy effectively increases HDL-C and lowers triglyceride and LDL-C levels while causing a shift toward larger, less atherogenic LDL particles. Niacin, alone or in combination, prevents progression and promotes regression of coronary atherogenic lesions and significantly reduces CHD-related morbidity and mortality. Statin monotherapy causes modest increases in HDL-C and decreases triglycerides, while more potently reducing LDL-C. Combinations of lipid-modifying agents may better address the full spectrum of lipoprotein abnormalities in some patients. Investigations have shown that combining statin therapy with niacin results in additive improvement in the major lipids and lipoproteins and improves clinical outcome. With recently broadened treatment recommendations, it seems likely that combination therapy will be increasingly deemed the appropriate choice for addressing a range of lipid abnormalities.

31. Manag Care. 2002 Sep;11(9 Suppl):4-9. Current drug treatments for lipid management. Stone NJ(1). Author information: (1)Feinberg School of Medicine, Northwestern University, Chicago, USA. PMID: 12369341 [Indexed for MEDLINE]

BACKGROUND: Both lipid-modifying therapy and antioxidant vitamins are thought to have benefit in patients with coronary disease. We studied simvastatin-niacin and antioxidant-vitamin therapy, alone and together, for cardiovascular protection in patients with coronary disease and low plasma levels of HDL. METHODS: In a three-year, double-blind trial, 160 patients with coronary disease, low HDL cholesterol levels and normal LDL cholesterol levels were randomly assigned to receive one of four regimens: simvastatin plus niacin, vitamins, simvastatin-niacin plus antioxidants; or placebos. The end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). RESULTS: The mean levels of LDL and HDL cholesterol were unaltered in the antioxidant group and the placebo group; these levels changed substantially (by -42 percent and +26 percent, respectively) in the simvastatin-niacin group. The protective increase in HDL2 with simvastatin plus niacin was attenuated by concurrent therapy with antioxidants. The average stenosis progressed by 3.9 percent with placebos, 1.8 percent with antioxidants (P=0.16 for the comparison with the placebo group), and 0.7 percent with simvastatin-niacin plus antioxidants (P=0.004) and regressed by 0.4 percent with simvastatin-niacin alone (P<0.001). The frequency of the clinical end point was 24 percent with placebos; 3 percent with simvastatin-niacin alone; 21 percent in the antioxidant-therapy group; and 14 percent in the simvastatin-niacin-plus-antioxidants group. CONCLUSIONS: Simvastatin plus niacin provides marked clinical and angiographically measurable benefits in patients with coronary disease and low HDL levels. The use of antioxidant vitamins in this setting must be questioned.

BACKGROUND: Nicotinic acid is an effective treatment for dyslipidemia. Patients are more tolerant of the extended-release form of nicotinic acid because it has a lower incidence of side effects, such as facial flushing, than the immediate-release formulation. OBJECTIVE: This study was designed to evaluate the efficacy and tolerability of an experimental extended-release formulation of nicotinic acid in Korean adults with mixed dyslipidemia as a regulatory requirement to allow marketing of this product in Korea. METHODS: This study was a multicenter, prospective, randomized, double-blind, and placebo-controlled trial. Patients with low high-density lipoprotein cholesterol (HDL-C) levels, high low-density lipoprotein cholesterol (LDL-C) levels, or high triglyceride levels were enrolled. Patients in the treatment group received 500 mg of extended-release niacin for 4 weeks and 1000 mg of extended-release niacin for the next 4 weeks. RESULTS: Twenty-five patients (24% males; mean [SD] age, 57.4 [6.9] years) comprised the treatment group, and 22 patients (5% males; mean [SD] age 61.8 [8.3] years) comprised the placebo group. After 8 weeks of treatment, HDL-C levels were increased significantly in the treatment group (17.6% vs -1.7%, respectively, from 35 [7] mg/dL to 42 [11] mg/dL in the treatment group and from 38 [6] mg/dL to 36 [7] mg/dL in the placebo group; P < 0.001). LDL-C levels were decreased significantly in the treatment group (-11.4% vs 3.6%, respectively, from 147 [33] mg/dL to 126 [22] mg/dL in the treatment group and from 146 [31] mg/dL to 148 [26] mg/dL in the placebo group; P = 0.003). The incidence of drug-related adverse events, including facial flushing in the treatment group, was not significantly different from that in the placebo group. CONCLUSIONS: The tested extended-release formulation of nicotinic acid increased HDL-C levels significantly but decreased LDL-C levels with a low incidence of facial flushing in this small, select group of Korean adults with mixed dyslipidemia.

Asian Indian dyslipidemia is characterized by: borderline high low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B; high triglycerides, low high-density lipoprotein (HDL) cholesterol and apoA1; and high lipoprotein(a) (lp[a]). We performed a controlled multicentric trial in India to evaluate the efficacy and safety of a fixed dose combination of lovastatin and niacin extended release (niacin(ER)) formulation in patients with moderate to severe dyslipidemia. Consecutive subjects that satisfied the selection criteria, agreed to an informed consent, and with no baseline presence of liver/renal disease or heart failure were enrolled in the study. After a 4-week run-in period there were 142 patients with LDL levels > or = 130 mg/dL. Eleven patients were excluded because of uncontrolled hyperglycemia and 131 patients were recruited. After baseline evaluation of clinical and biochemical parameters all subjects were administered lovastatin (20 mg) and niacin(ER) (500 mg) combination once daily. Dose escalation was done on basis of lipid parameters at 8 weeks and in 11 patients increased to lovastatin (20 mg) and niacin(ER) (1000 mg). An intention-to-treat analysis was performed and data was analyzed using nonparametric Wilcoxon signed rank test. Thirteen patients (10%) were lost to follow-up and 4 (3%) withdrew because of dermatological adverse effects: flushing, pruritus, and rash. The mean values of various lipid parameters (mg/dL) at baseline, and at weeks 4, 12, and 24 respectively were: total cholesterol 233.9 +/- 27, 206.3 +/- 27, 189.8 +/- 31, and 174.9 +/- 27 mg/dL; LDL cholesterol 153.4 +/- 22, 127.3 +/- 21, 109.2 +/- 27, and 95.1 +/- 23 mg/dL; triglycerides 171.1 +/- 72, 159.5 +/- 75, 149.2 +/- 45, and 135.2 +/- 40 mg/dL; HDL cholesterol 45.6 +/- 7, 48.9 +/- 7, 51.6 +/- 9, and 53.9 +/- 10 mg/dL; lp(a) 48.5 +/- 26, 40.1 +/- 21, 35.4 +/- 21, and 26.9 +/- 19 mg/dL; and apoA1/apoB ratio 0.96 +/- 0.7, 1.04 +/- 0.4, 1.17 +/- 0.5, and 1.45 +/- 0.5 (p < 0.01). The percentage of decline in various lipids at 4, 12, and 24 weeks was: total cholesterol 11.8%, 18.8%, and 25.2%; LDL cholesterol 17.0%, 28.8%, and 38.0%; triglyceride 6.8%, 12.8%, and 21.0%; l

IMPORTANCE: Niacin remains a therapeutic option for patients with cardiovascular disease, but recent studies have called into question the effectiveness of other drugs that increase high-density lipoprotein cholesterol levels. OBJECTIVE: To systematically review and evaluate the evidence supporting current US Food and Drug Administration-approved uses of niacin in cardiovascular disease prevention settings. DATA SOURCES: MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov, and TrialResults-center, from database inception to October 2017. STUDY SELECTION: The systematic review included clinical trials involving niacin as a treatment for cardiovascular disease. The meta-analysis included randomized clinical trials reporting niacin's effect, as exposure, on at least 1 long-term cardiovascular disease outcome. DATA EXTRACTION AND SYNTHESIS: Aggregate study-level data were extracted between November 2017 and January 2018 by 3 independent reviewers, and the analysis was performed in February 2018. Inverse-variance weighted methods were used to produce pooled risk ratios using random-effects models for between-study heterogeneity. Random effects-weighted metaregression analysis was used to assess the association of change in high-density lipoprotein cholesterol levels with the log risk ratio of the pooled results. MAIN OUTCOMES AND MEASURES: Cardiovascular disease, coronary heart disease mortality, and other cardiovascular events, including acute coronary syndrome, fatal and nonfatal stroke, revascularization, and major adverse cardiac events. RESULTS: Of 119 clinical trials, 17 documented niacin's effect on at least 1 cardiovascular disease outcome. The meta-analysis included 35 760 patients with histories of cardiovascular disease or dyslipidemia. Cumulative evidence found no preventive association of niacin with cardiovascular outcomes in secondary prevention. Stratified meta-analysis showed an association of niacin monotherapy with reduction of some cardiovascular events among patients without statin treatment (acute coronary syndrome: relative risk, 0.74; 95% CI, 0.58-0.96; stroke: relative risk, 0.74; 95% CI, 0.59-0.94; reva

BACKGROUND: The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain. DESIGN: We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes. METHODS: Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018). RESULTS: High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89-1.00, P = 0.05, I2 = 13%) or absolute risk (risk difference -0.0001, 95% CI -0.0014, 0.0011, P = 0.84, I2 = 28%). High-density lipoprotein cholesterol modifiers reduced the RR of myocardial infarction (RR 0.87, 95% CI 0.82-0.93, P < 0.001, I2 = 37%). This significant effect was derived by the use of fibrates (RR 0.80, 95% CI 0.73-0.87, P < 0.001, I2 = 22%) and meta-regression analysis showed that this benefit was consistent with an absolute reduction in low-density lipoprotein cholesterol. High-density lipoprotein cholesterol modifiers had no effect on stroke (RR 1.00, 95% CI 0.93-1.09, P = 0.94, I2 = 25%) or all-cause mortality (RR 1.02, 95% CI 0.97-1.08, P = 0.48, I2 = 49%). Meta-regression analyses failed to demonstrate a significant association of pharmacologically increased high-density lipoprotein cholesterol with key endpoints. In studies with background statin therapy, high-density lipoprotein cholesterol modifiers had no statistically significant impact on cardiovascular mortality, myocardial infarction, stroke or all-cause mortality ( P > 0.05). CONCLUSION: The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy.

BACKGROUND: Nicotinic acid (niacin) is known to decrease LDL-cholesterol, and triglycerides, and increase HDL-cholesterol levels. The evidence of benefits with niacin monotherapy or add-on to statin-based therapy is controversial. OBJECTIVES: To assess the effectiveness of niacin therapy versus placebo, administered as monotherapy or add-on to statin-based therapy in people with or at risk of cardiovascular disease (CVD) in terms of mortality, CVD events, and side effects. SEARCH METHODS: Two reviewers independently and in duplicate screened records and potentially eligible full texts identified through electronic searches of CENTRAL, MEDLINE, Embase, Web of Science, two trial registries, and reference lists of relevant articles (latest search in August 2016). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that either compared niacin monotherapy to placebo/usual care or niacin in combination with other component versus other component alone. We considered RCTs that administered niacin for at least six months, reported a clinical outcome, and included adults with or without established CVD. DATA COLLECTION AND ANALYSIS: Two reviewers used pre-piloted forms to independently and in duplicate extract trials characteristics, risk of bias items, and outcomes data. Disagreements were resolved by consensus or third party arbitration. We conducted random-effects meta-analyses, sensitivity analyses based on risk of bias and different assumptions for missing data, and used meta-regression analyses to investigate potential relationships between treatment effects and duration of treatment, proportion of participants with established coronary heart disease and proportion of participants receiving background statin therapy. We used GRADE to assess the quality of evidence. MAIN RESULTS: We included 23 RCTs that were published between 1968 and 2015 and included 39,195 participants in total. The mean age ranged from 33 to 71 years. The median duration of treatment was 11.5 months, and the median dose of niacin was 2 g/day. The proportion of participants with prior myocardial infarction ranged from 0% (4 trials) to 100% (2 trials, median proportion 48%); t

BACKGROUND: Niacin, a potent high-density lipoprotein cholesterol-raising drug, seems an attractive approach to reduce cardiac events in patients with or at risk of atherosclerotic cardiovascular disease. However, previous evidence for niacin has been challenged recently by negative outcomes in 2 large, randomized, controlled trials comparing niacin to placebo with background statin therapy. We studied the currently available evidence for the role of niacin treatment for reducing the risk of cardiovascular events in current practice. METHODS: A systematic review of randomized controlled trials in the MEDLINE, EMBASE, CINAHL, and Cochrane databases comparing niacin alone or combined with statin therapy was performed. We extracted trial level data, including basic characteristics and number of patients enrolled, duration of follow up, occurrence of adverse events, and cardiovascular-related outcomes. Random effects meta-analysis was conducted to estimate the risk ratio (RR) for individual trial endpoints. RESULTS: Thirteen trials (N = 35,206) were selected for final analysis. The mean follow-up duration was 32.8 months. Overall, niacin led to significant increases in serum high-density lipoprotein cholesterol levels from baseline trial enrolment by 21.4%, 9.31 (95% confidence interval [CI] 5.11-13.51) mg/dL. However, we did not observe any differences in all-cause mortality rates (RR 0.99; 95% CI 0.88-1.12) between niacin and control arms. Further, niacin treatment was associated with a trend toward lower risk of cardiovascular mortality (RR 0.91; 95% CI 0.81-1.02), coronary death (RR 0.93; 95% CI 0.78-1.10), nonfatal myocardial infarction (RR 0.85; 95% CI 0.73-1.0), revascularization (coronary and noncoronary) (RR 0.83; 95% CI 0.65-1.06), and stroke (RR 0.89; 95% CI 0.72-1.10), compared with control. CONCLUSION: Niacin therapy does not lead to significant reductions in total or cause-specific mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease.

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This systematic review and meta-analysis investigated the effects of established and novel treatment strategies, specifically targeting HDL, on inhibition of atherosclerosis in cholesteryl ester transfer protein-expressing animals, and the prevention of clinical events in randomised controlled trials. Linear regression analyses using data from preclinical studies revealed associations for TC and non-HDL-C and lesion area (R(2)=0.258, P=0.045; R(2)=0.760, P<0.001), but not for HDL-C (R(2)=0.030, P=0.556). In clinical trials, non-fatal myocardial infarction risk was significantly less in the treatment group with pooled odd ratios of 0.87 [0.81; 0.94] for all trials and 0.85 [0.78; 0.93] after excluding some trials due to off-target adverse events, whereas all-cause mortality was not affected (OR 1.05 [0.99-1.10]). Meta-regression analyses revealed a trend towards an association between between-group differences in absolute change from baseline in LDL-C and non-fatal myocardial infarction (P=0.066), whereas no correlation was found for HDL-C (P=0.955). We conclude that the protective role of lowering LDL-C and non-HDL-C is well-established. The contribution of raising HDL-C on inhibition of atherosclerosis and the prevention of cardiovascular disease remains undefined and may be dependent on the mode of action of HDL-C-modification. Nonetheless, treatment strategies aimed at improving HDL function and raising apolipoprotein A-I may be worth exploring.

Endothelial dysfunction is an independent predictor of incident atherosclerotic cardiovascular disease (ACVD). Niacin possesses high-density lipoprotein (HDL)-elevating, antioxidant and anti-inflammatory properties, all potentially contributing to the amelioration of endothelial function. However, controversies exist among trials reporting the effects of niacin on endothelium-dependent flow-mediated dilation (FMD) as a reliable surrogate of endothelial function. The objective of this study was to assess the effect of niacin on brachial artery FMD using a meta-analysis of available evidence. MEDLINE and Scopus databases were searched for randomized controlled trials investigating the impact of niacin therapy on brachial artery FMD. Meta-analysis of eligible studies was conducted using a random-effects model. Pooled effects were measured by weighted mean difference (WMD) and 95% confidence intervals (CIs). Quality assessment, and subgroup, meta-regression and sensitivity analyses were conducted using standard methods. Among 596 citations, 19 full-text articles were read and seven were found to be eligible for inclusion. Eligible studies involved 441 subjects comprising 228 in the niacin and 213 in the control groups. Niacin therapy significantly improved FMD (WMD: 1.98%; 95% CI: 0.91-3.05%; p = 0.0003) and this effect was robust in the sensitivity analysis. The effect size was greater in the subgroup of studies administering higher doses of niacin (≥ 2000 mg/day) as well as those studies administering niacin for primary prevention of ACVD. Meta-regression indicated no association between niacin-induced changes in FMD and changes in plasma HDL-cholesterol, low-density lipoprotein-cholesterol or triglycerides. None of the included studies could find any significant effect of niacin on nitroglycerin-mediated dilation. In conclusion, treatment with niacin improves endothelial function.

PURPOSE: Clinical trials have shown that niacin and its analog, niacinamide, significantly reduce serum phosphate in patients undergoing dialysis. This review aimed to assess the benefits and harm of niacin and niacinamide in renal dialysis patients. METHODS: PubMed, EMBASE, and Cochrane Library were searched, without language limitation, randomized controlled trials (RCTs). Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, version 5.2, was used for meta-analysis. RESULTS: Five RCTs with a sample size of 230 patients were included. The meta-analysis showed that niacin and niacinamide significantly decreased serum phosphorus levels [weight mean difference (WMD) -0.88; 95 % confidence interval (CI) -1.19 to -0.57] as well as the calcium × phosphorus product (Ca × P) (WMD -9.15; 95 % CI -13.23 to -5.08), and increased high-density lipoprotein (HDL) levels (WMD 9.30; 95 % CI 5.86-12.74) in renal dialysis patients. Niacin significantly increased the risk of flushing [relative risk (RR) 33; 95 % CI 4.71-232.12] in these patients, while the risk of thrombocytopenia was significantly increased in the niacinamide group (RR 2.82; 95 % CI 1.14-6.94). However, sensitivity analysis showed that our finding regarding thrombocytopenia should be regarded with a low degree of certainty. CONCLUSION: Niacin and its analog effectively improved phosphorus metabolism in renal dialysis patients. However, niacin can cause flushing and niacinamide probably cause thrombocytopenia. Further larger sample size and well-designed RCTs are needed.

PURPOSE: This systematic review was performed to summarize published experience using low density lipoprotein particle number (LDL-P) to monitor the efficacy of lipid-lowering pharmacotherapies. METHODS: Studies were identified from a literature search of MEDLINE (January 1, 2000 - June 30, 2012); and abstract searches of select conferences. All accepted studies reported mean (or median) nuclear magnetic resonance (NMR)-based LDL-P values for at least 10 subjects receiving lipid lowering pharmacotherapy. RESULTS: Searches revealed 36 studies (with 61 treatment arms) in which LDL-P measurements were reported pre- and post-treatment. Most studies also reported changes in low-density lipoprotein cholesterol (LDL-C), but fewer studies reported changes in apolipoprotein B (apoB)(n = 20) and non-HDL-C (n = 28). Treatments included statins (22 arms/15 studies), fibrates (7 arms/7 studies), niacin (7 arms/6 studies), bile acid sequestrants (5 arms/2 studies), an anti-apoB oligonucleotide (2 arms/2 studies), combination therapies (8 arms/6 studies), anti-diabetics (5 arms/4 studies), and, other treatments (5 arms/2 studies). Lipid-lowering pharmacotherapy resulted in reductions in mean LDL-P in all but two studies. In several statin studies, the percent reductions in LDL-P were smaller than reductions in LDL-C, comparable changes were reported when LDL-P and apoB, were reported. CONCLUSIONS: Study-level data from this systemic review establish that different lipid lowering agents can lead to discordance between LDL-P and LDL-C, therefore, basing LDL-lowering therapy only on the achievement of cholesterol goals may result in a treatment gap. Therefore, the use of LDL-P for monitoring lipid-lowering therapy, particularly for statins, can provide a more accurate assessment of residual cardiovascular risk.

OBJECTIVES: This study sought to assess the efficacy of niacin for reducing cardiovascular disease (CVD) events, as indicated by the aggregate body of clinical trial evidence including data from the recently published AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial. BACKGROUND: Previously available randomized clinical trial data assessing the clinical efficacy of niacin has been challenged by results from AIM-HIGH, which failed to demonstrate a reduction in CVD event incidence in patients with established CVD treated with niacin as an adjunct to intensive simvastatin therapy. METHODS: Clinical trials of niacin, alone or combined with other lipid-altering therapy, were identified via MEDLINE. Odds ratios (ORs) for CVD endpoints were calculated with a random-effects meta-analyses. Meta-regression modeled the relationship of differences in on-treatment high-density lipoprotein cholesterol with the magnitude of effect of niacin on CVD events. RESULTS: Eleven eligible trials including 9,959 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CVD event (OR: 0.66; 95% confidence interval [CI]: 0.49 to 0.89; p = 0.007) and major coronary heart disease event (OR: 0.75; 95% CI: 0.59 to 0.96; p = 0.02). No significant association was observed between niacin therapy and stroke incidence (OR: 0.88; 95% CI: 0.5 to 1.54; p = 0.65). The magnitude of on-treatment high-density lipoprotein cholesterol difference between treatment arms was not significantly associated with the magnitude of the effect of niacin on outcomes. CONCLUSIONS: The consensus perspective derived from available clinical data supports that niacin reduces CVD events and, further, that this may occur through a mechanism not reflected by changes in high-density lipoprotein cholesterol concentration.