Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study

Abstract

Low HDL-cholesterol (<1.02 mmol/L [40 mg/dL] in men or <1.29 mmol/L [50 mg/dL] in women) occurs in about one-third of European patients with dyslipidemia and is an independent cardiovascular risk factor. Simultaneous correction of low HDL-cholesterol and high total-cholesterol and LDL-cholesterol may provide reductions in cardiovascular morbidity and mortality beyond those possible with statins alone. Nicotinic acid (niacin in the US) is the most effective means of increasing HDL-cholesterol available and has been shown to reduce cardiovascular event rates significantly. Niaspan (prolonged-release nicotinic acid) provides a convenient, once-daily means of administering nicotinic acid. Clinical studies with Niaspan have demonstrated marked, long-term increases in HDL-cholesterol with additional useful benefits on triglycerides, LDL-cholesterol, and lipid sub-profiles. The NAUTILUS study demonstrated the beneficial efficacy and tolerability profiles of Niaspan in a usual-care setting. The most common side-effect of Niaspan is flushing, which infrequently causes treatment discontinuation and which usually subsides over continued treatment. The ARBITER 2 and ARBITER 3 studies showed 1-2 years of treatment with Niaspan plus a statin induced regression of atherosclerosis in patients with coronary artery disease. The effect of Niaspan-statin treatment, relative to a statin alone, on clinical cardiovascular outcomes is currently under evaluation. Niaspan represents a practical means of correcting low HDL-cholesterol, an independent risk factor for adverse cardiovascular outcomes.

Figure 1

Adjusted coronary heart disease mortality rates according to HDL-cholesterol and LDL-cholesterol levels during 21 years of follow-up in 8586 Israeli men without coronary heart disease at baseline. Cut-off values to define low/high lipid levels were 0.9 mmol/L for HDL-cholesterol and 5.2 mmol/L for total-cholesterol. RR: risk ratios compared with corresponding low HDL-cholesterol group (adjusted for age, systolic blood pressure, smoking, and diabetes). Drawn from data presented by Goldbourt et al (1997).

Figure 2

Dose-related effect of Niaspan^® (500–3000 mg/day) on lipid parameters in a 25-week, double-blind, randomized trial in 131 patients with hyperlipidemia. *p < 0.05 vs placebo. Effects of placebo have been omitted for clarity. Drawn from data presented by Goldberg et al (2000).

Figure 3

Comparison of effects on lipids of combinations of nicotinic acid with a statin in comparison with a combination of a statin with ezetimibe or rosuvastatin monotherapy in a 12-week, open-label, randomized trial in 292 patients indicated for LDL-cholesterol lowering therapy. Patients received rosuvastatin (20–40 mg), rosuvastatin plus Niaspan^® (10/1000 mg or 20/1000 mg), atorvastatin plus Niaspan^® (20/1000 mg or 40/2000 mg), or simvastatin plus ezetimibe (20/10 mg or 40/10 mg). Significance values are from ANOVA across groups. Drawn from data presented by McKenney et al (2006).

Figure 4

Long-term (96 weeks) effects of Niaspan^® (up to 3000 mg/day) on the lipid profile in patients with dyslipidemia, with (n = 122) or without (n = 225) concomitant statin administration. Drawn from data presented by Guyton and Capuzzi (1998).

Figure 5

Flushing with Niaspan^® in the NAUTILUS trial, a 15-week evaluation of Niaspan^® at doses up to 2000 mg/day in 566 patients with dyslipidemia and low HDL-cholesterol managed in the usual care setting. Reproduced with permission from Vogt A, Kassner U, Hostalek U, et al 2006. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. Curr Med Res Opin, 22:417-25.

Figure 6

Mean changes in HDL-cholesterol and triglycerides in subgroups of the NAUTILUS population based on gender, presence/absence of the metabolic syndrome (MS), hypercholesterolemia (HC), isolated low HDL-cholesterol (ILH), receipt/non-receipt of statins, presence/absence of diabetes mellitus (DM), and age. Drawn from data presented by Vogt et al 2006a, , , .

Figure 7

Treatment assignments in the double-blind, randomized, ARBITER 2 study and its open-label follow-up study, ARBITER 3. Numbers of patients shown are those completing each phase. The duration each phase trial was 1 year; the Niaspan^® daily dose was 1000 mg. Adapted with permission from Taylor AJ, Lee HJ, Sullenberger LE. 2006. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin, 22:2243-50.