Nicotinic acid therapy

Neomycin/nicotinic acid combination therapy lowered Lp(a) markedly in some patients, but nicotinic acid alone was not effective (G35, Ml9). On the other hand, in a subgroup of patients with hypertriglyceridemia, Carlson (C2) and Seed (S27) reported a positive effect of nicotinic acid therapy on Lp(a) levels and ascribed it to an inhibition of synthesis of apo-B. 

Compliance with nicotinic acid therapy can be poor because the drug can produce an intense cutaneous flush. This can be reduced by beginning the drug in... 

Baggenstoss AH, Christensen NA, Berge KG, Baldus WP, Spieckerman RE, and Ellefson RD (1967) Fine structural changes in the liver in hypercholesterolemic patients receiving long-term nicotinic acid therapy. Mayo Clinic Proceedings 42, 385-99. 

A. Garg and S.M. Grundy, Nicotinic acid therapy for dyslipidemia in non-in-SLilin-dependent diabetes mellitus,... 

Elevated uric acid level is a common side effect of nicotinic acid therapy. Thus, gout would be exacerbated. 

References are given in this paper to some earlier work on nicotinic acid therapy. 

Shepherd, J., Packard, C.J., Patsch, J.R., Gotto, A.M., and Taunton, O.D., 1979. Effects of nicotinic acid therapy on plasma high density lipoprotein subfraction distribution and composition and on apoUpoprotein A metabolism. Journal of Clinical Investigation. 63 858-867. 

Kohn, R. M. and Montes, M., 1969, Hepatic fibrosis following long acting nicotinic acid therapy a case report. Am. J. 

Nicotinic acid therapy in coronary disease. Amer. Heart J. 63, 143 (1962). 

O Reilly, P. 0. Some clinical aspects of nicotinic acid therapy in hypercholesteremia. Canad. med. Ass. J. 78, 402 (1958). 

Pardue, W. D. Severe liver dysfunction during nicotinic acid therapy. J. Amer. med. Ass. 175, 137 (1961). 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

Perform liver function tests on all patients during therapy with nicotinic acid. Monitor serum transaminase levels, including ALT and AST, before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (at approximately 6-month intervals). Discontinue the drug if the transaminase levels show evidence of progression, particularly if they rise to 3 times the upper limit of normal and are persistent or if they are associated with symptoms of nausea, fever, or malaise. Consider liver biopsy if elevations persist beyond discontinuation. 

A few cases of advanced cystoid macular edema have been reported in the older literature these took months to resolve once nicotinic acid was withdrawn (SEDA-14, 331 SEDA-20, 191 15,20). Four new cases have been added in patients who took nicotinic acid 2-4.5 g/day (21,22). The first symptoms of blurred vision appeared 1-18 months after the start of therapy. Withdrawal of nicotinic acid resulted in improvement of visual acuity and resolution of the cystoid macular edema within 1-2 months. A particular feature that distinguishes this form of maculopathy is the absence of leakage on fluorescein angiography. Retinal edema, when it occurs, will abate on withdrawal of nicotinic acid (15). 

Skin problems can be persistent in a proportion of patients, variously estimated at 10-59%, and this can severely limit adherence to therapy. The skin reaction can be ameliorated by concomitant use of non-steroidal anti-inflammatory drugs such as aspirin and indometacin (SEDA-15, 412). Transient exanthems, pruritus, and sometimes wheals are seen, as well a uniform dryness and scaling of the epidermis, brown pigmentation, and even on occasion an acanthosis nigricans-like dermatosis (15). Persistent rashes can also occur. Doses in excess of 5 g/day are routinely associated with skin manifestations and can on occasion cause liver damage, gout and ulcer formation. These reactions can be associated with nicotinic acid rather than nicotinamide, which is sometimes recommended as an alternative (37). Increased hair loss has been described. 

Garg A, Grundy SM. Nicotinic acid as therapy for dyslipi-demia in non-insulin-dependent diabetes mellitus. JAMA 1990 264(6) 723-6. 

A meta-analysis was performed on randomized trials assessing lipid-lowering therapy in 698 patients with PAD who were treated with a variety of therapies, including diet, cholestyramine, probucol, and nicotinic acid, for four months to three years (8). There was a significant difference in total mortality [0.7% in the treated patients, as compared with 2.9% in the patients given placebo (p = NS)], with an additional reduction in disease progression, as measured by angiography and the severity of claudication. 

Prior to 1987, the lipid-lowering armamentarium was limited essentially to dietary changes (reductions in saturated fats and cholesterol), the bile acid sequestrants (cholestyramine and colestipol), nicotinic acid (niacin), the fibrates, and probucol. Unfortunately, all of these treatments have limited efficacy or tolerability or both. Substantial reductions in LDL cholesterol (up to 47%) accompanied by increases in HDL cholesterol of up to 32% could be achieved by the combination of a lipid-lowering diet, a bile acid sequestrant, and the subsequent addition of nicotinic acid (Illingworth et al., 1981). However, this therapy is not easy to administer or tolerate and was therefore often unsuc-... 

Therapy with nicotinic acid plus bile acid binding resin revealed improvements in the biochemical risk factors, and also proved to reduce the thickness of atberosderfjtic lesions (Blankcnhom et al., 1993). 

---