In 2013 we have already published two commentaries on niacin (Commentary on Niacin vs Ezetimibe as add on to Statin) and (Examination of the Recently Announced Preliminary Results of the HPS2-THRIVE Study), specifically extended release available as Niaspan, a seemingly potent lipid- and lipoprotein-modulating drug that dates back to the 1960’s. Initially it was used to reduce elevated cholesterol levels but eventually it was found to also raise HDL-C which for a variety of reasons was assumed to be very desirable (thought being that if low HDL-C is a strong CV risk factor, then raising it must be beneficial). Also of interest was niacin’s ability to significantly reduce lipoprotein (a) mass [Lp(a)]. Indeed, a group entitled European Atherosclerosis Society Consensus Panel issued a statement strongly advising niacin be used for CV benefits in patients with elevated Lp(a) . Interestingly that panel noted there was virtually no clinical trial support for this recommendation other than the fact that niacin does indeed reduce Lp(a) mass. Most lipidologists agreed with the belief that even if reducing Lp(a) does not matter, niacin would at least reduce apolipoprotein B (apoB) which is seemingly always desirable. NCEP ATP-III simply advocated achieving LDL-C goals in persons with risk related to Lp(a) issues.
Recent trials [The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM HIGH) and large Heart Protection Study 2: Treatment of HDL to Reduce the Incidence of Vascular Events (HPS THRIVE 2)] have not shown additional event reduction in well-treated patients with stable CHD related to adding niacin to a statin or statin/ezetimibe regimen [2,3]. To say the results of those studies were a shock to the lipidology community is an understatement. AIM HIGH (all of the patients had low HDL-C at baseline) was published first and for those who believed niacin’s benefit was related to raising HDL-C, the results were a punch to the jaw. Despite a substantial (25%) HDL-C increase (remember the old well accepted but never proven caveat that for every 1% rise in HDL-C there is a 3% event reduction) there was no CV outcome improvement. The usual side effects associated with niacin were present including a questionable nonsignificant rise in ischemic stroke. Then along came the still not published HPS THRIVE 2 (baseline HDL-C was not an enrollment criteria) where again the addition of niacin to a statin or statin/ezetimibe regimen provided no additional outcome benefit. Common to both AIM HIGH and HPS THRIVE 2 was the fact that the lifestyle with statin or statin/ezetimibe had normalized LDL-C, non-HDL-C and apoB. Thus niacin was being added to patients who were at those goals (keeping in mind that there is no NCEP ATP-III goal for HDL-C). Should we really have expected niacin, whose primary mechanism of action is to lower apoB (or its lipid surrogates) to do anything to CV events in persons with normal apoB? The answer is yes if raising HDL-C or lowering Lp(a) mass is critical to event reduction (well accepted concepts that have never ever been proven in any type of trial). Well we may have those answers now and at this point one has to reasonably conclude the evidence is strong that in patients on LDL-receptor inducing drugs (statins or statin + ezetimibe) raising HDL-C (note – niacin also raises apoA-I, but not apoA-II or total HDL-P)  or reducing Lp(a) mass with niacin provides no benefit in folks who are at apoB (LDL-C, non-HDL-C) goal.
 European Atherosclerosis Society Consensus Panel. Lipoprotein(a) as a cardiovascular risk factor: current status. European Heart Journal 2010;31:2844–2853. The AIM-HIGH Investigators Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N Engl J Med 2011;365:2255-67.
 Presentation by Jane Armitage on behalf of the HPS2 THRIVE group to the National Lipid Association Annual Scientific sessions, Las Vegas NV June 2013.
 Otvos, JD.The surprising AIM-HIGH results are not surprising when viewed through a particle lens. Journal of Clinical Lipidology (2011) 5, 368–370.
 John J. Albers, et al. Relationship of Apolipoproteins A-1 and B, and Lipoprotein (a) to Cardiovascular Outcomes in the AIM-HIGH Trial in press JACC 10.1016/j.jacc.2013.06.051 Coronary Drug project group. Clofibrate and Niacin in Coronary Heart Disease. JAMA 1975;231:360-381.
 Fifteen Year Mortality in Coronary Drug Project Patients: Long Term Benefit with Niacin. JACC 1986;8:1245-55.
 Reduction of Mortality in the Stockholm Ischaemic Heart Disease Secondary prevention Study by Combined Treatment with Clofibrate and Nicotinic Acid. Acta Med Scand 1988;223:405-418. Masana, A. Cabré, N. Plana. HPS2-THRIVE results: Bad for niacin/laropiprant, good for ezetimibe? Atherosclerosis 2013;229:449-450.
 Masana, A. Cabre, N. Plana. HPS2-THRIVE results: Bad for Niacin/laropiprant, good for ezetimibe? Atherosclerosis 2013; 229:449-450.
 Nihar R. Desai, et al. AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy. (Circulation. 2013;128:962-969.)
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