The final word on the additive power of niacin on top of aggressive statin therapy will only come from RCTs powered for clinical event endpoints, and the use of surrogate markers as reliable indicators of future CVD events should be viewed with healthy skepticism. 2008 Oct;14(8 Suppl):S3-28; quiz S30-1. For adults with increased metabolic risk, intensified lifestyle changes remain an important target of therapy; weight loss can have substantial impact on triglyceride levels and inflammatory markers. Watts G.F. and Chan D.C.: Association between uric acid and brachial-ankle pulse wave velocity: secondary analysis of data from a cross-sectional study. : A meta-analysis of 41 randomized trials" COVID-19 is an emerging, rapidly evolving situation. CHD = coronary heart disease; cIMT = carotid intima-media thickness; CVD = cardiovascular disease; ERN = extended-release niacin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; MRI = magnetic resonance imaging; N/A = not available; RCT = randomized, clinical trial. 23. AIM-HIGH Investigators: Sharma K., Blaha M.J., Blumenthal R.S. A subgroup analysis of outcomes by baseline lipid status (such as LDL-C ≥70 mg/dl vs. <70 mg/dl) was not presented in the main paper. "Carotid intimal thickness as a surrogate for cardiovascular disease events in trials of HMG-CoA reductase inhibitors" HATS also showed a reduction in the progression of coronary stenosis with the niacin-simvastatin combination compared with placebo (Table 1). Taylor A.J., Sullenberger L.E., Lee H.J., Lee J.K. and Grace K.A. and Musunuru K.: The baseline mean LDL-C in AIM-HIGH was lower than in the HALTS and Oxford studies, which may partially explain the lack of benefit for additional niacin therapy. Dal-OUTCOMES (N = 15,600) randomized patients with acute coronary syndromes to dalcetrapib or placebo and is anticipated to be completed in 2013. Am Heart J2008; 156: 826. 8. Circulation2005; 111: 2525. Foam cell accumulation in the carotid arteries, the principal pathological feature of an increased cIMT, is likely the main component that is capable of regression; direct comparisons of cIMT and magnetic resonance imaging–measured regression in the context of statins are not available. Observational studies have shown that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased CVD risk. "Extended-release Niacin or Ezetimibe and carotid intima-media thickness" : Get the latest public health information from CDC: https://www.coronavirus.gov. N Engl J Med2007; 357: 1301. Epub 2011 Feb 2. Espeland M.A., O'Leary D.H., Terry J.G.et al. The number of clinical endpoints in HATS and FATS was modest, although there was a reduction in the CVD primary endpoint in HATS with simvastatin-niacin versus placebo when antioxidants were not used. and Wolski K.: Copyright © 2012 American College of Cardiology Foundation. It remains unknown whether more aggressive LDL-C reduction with a more potent statin would be more effective than adding a second lipid-modifying agent to a less potent statin or lower statin dose. Niacin combination therapy raises HDL cholesterol and decreases dense LDL and intermediate density lipoprotein cholesterol. The incidence of CVD events was lower in the niacin group (2 [1%] vs. 9 [5%], p = 0.029), although the study was not powered for clinical endpoints (9). On the other hand, the results of the NIA (National Institute on Aging) Plaque study (11) did not suggest a benefit of the addition of niacin to statin therapy among well-treated older participants with high vascular risk but higher mean HDL-C levels. The HALTS trial (9) compared the effects of 2 adjunctive lipid-lowering medications, ezetimibe and ERN, added to background statin therapy. J Am Coll Cardiol2010; 55: 2721. . Previously, small randomized, clinical trials of niacin plus statins showed that modest regression of carotid atherosclerosis is possible in individuals with CVD, CVD risk equivalents, or atherosclerosis. In addition, it remains unclear whether a reduction in cIMT progression or actual regression obtained with a pharmacological treatment is necessarily followed by a decrease in coronary atherosclerosis and events. . "Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence" The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial, which compared combined niacin/simvastatin with simvastatin alone, failed to demonstrate an incremental benefit of niacin among patients with atherosclerotic CVD and on-treatment low-density lipoprotein cholesterol values <70 mg/dl, but this study had some limitations. Lancet2007; 369: 1090. 2016 Sep 9;15(1):151. doi: 10.1186/s12944-016-0323-3. Taylor A.J., Lee H.J. Individuals less able to handle the side effects of niacin might also be less compliant with other secondary prevention measures. Nine years after termination of the Coronary Drug Project, niacin still conferred an 11% reduction in all-cause mortality compared with placebo (p = 0.0004) (5). 15. Clipboard, Search History, and several other advanced features are temporarily unavailable. : Journal of the American College of Cardiology, Reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Trial With Previous Surrogate Endpoint Trials, "Of mice and men: Blowing away the cobwebs from the mechanisms of action of niacin on HDL metabolism", "Novel HDL-directed pharmacotherapeutic strategies", "Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease", "Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B", "Fifteen year mortality in Coronary Drug Project patients; long term benefit with niacin". Taylor A.J., Lee H.J. . Fleg J.L., Mete M., Howard B.V.et al. 2. deGoma E.M. and Rader D.J. Triglyceride lowering (and, thus, further apolipoprotein B lowering) is also important, and non–HDL-C is a secondary target goal in the Adult Treatment Panel III guidelines. Lee J.M., Robson M.D., Yu L.M.et al. For example, despite substantial increases in HDL-C levels conferred by treatment with the CETP inhibitor torcetrapib, this did not translate to any benefit (rather increased harm) in the ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events) trial, although blood pressure increases related to increased aldosterone may have negated the favorable changes in lipids (14). The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Trial: To Believe or Not to Believe? . Regression of carotid plaque was seen with aggressive standard medical therapy including statins, but a similar degree of regression occurred in both the niacin and placebo arms. "Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy" : Folsom A.R., Kronmal R.A., Detrano R.C.et al. Costanzo P., Perrone-Filardi P., Vassallo E.et al. 22. Arterioscler Thromb Vasc Biol2008; 28: 1892. NIH N Engl J Med2001; 345: 1583. In observational studies, cIMT predicts future CHD and stroke (15).