Effects Of Extended-release Niacin Research Articles

The effect of 24 months of combination statin and extended-release niacin on carotid intima‐media thickness: ARBITER 3

ABSTRACTObjective: The ARBITER 2 trial showed that extended-release niacin (ERN) when added to statin monotherapy slowed the progression of carotid atherosclerosis over 12 months. Whether longer treatment with ERN would have a greater effect on carotid intima.media thickness (CIMT) is unknown.Research design and methods: We examined the long-term effects of ERN on high density lipoprotein (HDL-C) cholesterol and CIMT during 12.24 months treatment with ERN in ARBITER 2 participants who were either continued or were crossed over (from placebo) to ERN 1000 mg daily.Main outcome measures: Among 149 subjects completing ARBITER 2, 130 (88%) enrolled in ARBITER 3. The prespecified primary endpoints were the within-group change in CIMT and HDL.C in patients receiving placebo for 12 months (n = 71), ERN for 12 months (comprised of subjects from ERN treatment during ARBITER 2 (n = 78) and those crossed over to ERN from placebo after ARBITER 2 (n = 47)), and ERN for 24 months spanning ARBITER 2 and 3 (n = 57). Five subjects discontinued the study due to flushing side effects. The study was completed by 104 subjects (47 crossed over from placebo; 57 with ERN continued from ARBITER 2).Results: HDL.C increased in the ERN group from 39.5 ± 6.7 to 48.6 ± 13.3 mg/dl (p < 0.001) along with modest reductions in LDL.C and TG. Among 125 participants treated with ERN for 12 months, there was a net regression of CIMT of. 0.027 ± 0.011 mm (p < 0.001 vs. placebo). Among 57 participants treated with ERN for 24 months, there was additional significant regression of CIMT of. 0.041 ± 0.021 mm (p = 0.001 vs. placebo). Controlling for changes in LDL and triglycerides, only changes in HDL.C were independently associated with regression of CIMT (b =. 0.25; p = 0.001).Conclusion: When added to statin therapy, ERN significantly increases HDL.C and induces atherosclerosis regression measured by CIMT over 24 months. Limitations to this study include its open-label design and the inability to relate CIMT effects to clinical outcomes.

Effects of Extended-Release Niacin on Lipoprotein Particle Size, Distribution, and Inflammatory Markers in Patients With Coronary Artery Disease

In this study, niacin was added to existing therapy for 3 months in 54 subjects with stable coronary artery disease. Average total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were similar between groups. Three months of niacin treatment increased total HDL by 7.5% and decreased triglycerides by 15% compared with baseline values (p <0.005 for each), whereas total cholesterol and LDL levels remained unchanged. Addition of niacin resulted in a 32% increase in large-particle HDL (p <0.001), an 8% decrease in small-particle HDL (p = 0.0032), an 82% increase in large-particle LDL (p = 0.09), and a 12% decrease in small-particle LDL (p = 0.008). Niacin decreased lipoprotein-associated phospholipase A2 and C-reactive protein levels (20% and 15%, respectively, p <0.05 for the 2 comparisons). No significant changes from baseline were seen in any tested parameter in subjects who received placebo. In conclusion, addition of niacin to existing medical regimens for patients with coronary artery disease and already well-controlled LDL levels favorably improves the distribution of lipoprotein particle sizes and inflammatory markers in a manner that would be expected to confer atheroprotection. The effect of altering lipoprotein particle distribution and inflammatory markers on surrogate markers of atherosclerosis and clinical cardiovascular events in this population remains unclear.

A meta-analysis of randomized controlled studies on the effects of Extended-Release niacin in women

The present meta-analysis pooled data from 5 double-blind, placebo-controlled studies in 432 patients with dyslipidemia treated with various doses of extended-release niacin. Data were analyzed for possible gender differences in response to treatment. At all doses, mean decreases in low-density lipoprotein cholesterol were greater in women than in men; differences were significant at doses of 1,000 mg (6.8% vs 0.2%, p = 0.006), 1,500 mg (11.3% vs 5.6%, p = 0.013), 2,000 mg (14.8% vs 6.9%, p = 0.010), and 3,000 mg (28.7% vs 17.7%, p = 0.006). Decreases in triglyceride levels also tended to be greater in women than in men but reached significance only at the 1,500-mg dose (28.6% vs 20.4%, p = 0.040). No similar trends or significant gender differences were noted in levels of lipoprotein(a) and high-density lipoprotein cholesterol. This meta-analysis confirms that women respond as well as men, and possibly slightly better, to treatment with extended-release niacin and that it is a safe and effective treatment option for women with dyslipidemia.

Effects of extended-release niacin on lipoprotein subclass distribution

The efficacy of extended-release niacin (niacin ER) on lipoprotein subclasses was evaluated in patients with primary hypercholesterolemia using a proton nuclear magnetic resonance method. Paired plasma samples collected at baseline and after 12 weeks’ treatment with niacin ER 1,000 (n = 21) or 2,000 (n = 20) mg/day or placebo (n = 19) were available for 60 eligible patients from a previous multicenter, randomized, controlled trial. Niacin ER increased high-density lipoprotein (HDL) cholesterol and decreased low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein triglycerides in a dose-dependent manner relative to placebo. Niacin ER increased large HDL particles (H5 and H4, corresponding to the HDL 2ab fraction) without having a net effect on small HDL particles (H3, H2, and H1, corresponding to the HDL 3abc fraction). It also decreased smaller, denser LDL particles (L1 and L2) and increased the larger, more buoyant L3 subclass. The inhibitory effect of niacin ER on very low-density lipoprotein was evident on the larger particles (V6, V5, V4, and V3 subclasses) rather than the smaller ones (V2 and V1). The results show that niacin ER produces a beneficial effect on lipoprotein subclasses, specifically decreasing the more atherogenic small, dense LDL particles and enhancing the cardioprotective large HDL particles.

Lp A-I and Niacin

Increasing evidence from epidemiological, clinical, and basic mechanistic studies supports the importance of HDL in preventing or even reversing atherosclerosis. The well-known structural and compositional diversity of HDL subfractions seems to be an important, if still somewhat unclear, factor in the atheroprotective potential of a given HDL particle. Perhaps as important as the parameter of particle size is that of apolipoprotein content of HDL. HDL particles which lack apo A-II (Lp A-I) appear to associate with reduced atherosclerosis risk1 and are reported to be better cholesterol acceptors in some2,3 although not all studies4 as compared with HDL with apo A-II (Lp A-I/A-II). See page 1783 Niacin generally is considered the most effective agent for raising HDL levels, typically increasing HDL-C by 30%.5 The mechanism of this effect has been shown, by in vivo human turnover studies, to be a decrease in its fractional catabolic rate6,7 Interestingly, despite the clinical importance of both niacin and Lp A-I levels, the impact of the former on the latter has been little studied. One earlier intensive study of a small number of subjects showed that niacin selectively raised Lp A-I levels while Lp A-I/A-II declined somewhat,8 but this question appears not to have been further tested in almost two decades since. Gemfibrozil also is effective in raising HDL levels, although generally less than half as much as niacin.9 The major HDL-raising mechanism of gemfibrozil appears to be an increase in production of apo A-I, as demonstrated by Saku et al10 in vivo and by Jin et al11 in vitro. Surprisingly, the effect of gemfibrozil on levels of Lp A-I and Lp A-I/A-II has not been reported, to our knowledge. Sakai and coworkers12 have now addressed some of the gaps in our understanding of the …

Effects of extended-release niacin on lipoproteins and glycemic control in patients with type 2 diabetes mellitus: Results of a randomized, double-blind, placebo-controlled multicenter trial Scott M. Grundy, Gloria L. Vega, Mark E. McGovern, for the Diabetes Multicenter Research Group. University of Texas Southwestern Medical Center, Dallas, TX

Effects of extended-release niacin on lipoproteins and glycemic control in patients with type 2 diabetes mellitus: Results of a randomized, double-blind, placebo-controlled multicenter trial Scott M. Grundy, Gloria L. Vega, Mark E. McGovern, for the Diabetes Multicenter Research Group. University of Texas Southwestern Medical Center, Dallas, TX