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

Figures & data

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).

Table 1 Prevalence of low HDL-cholesterol in the Pan-European Survey of HDL-cholesterol (Bruckert et al 2005a)

	Receiving lipid-modifying treatment	No lipid-modifying treatment
Low HDL-cholesterol (%)
Men	32.5	34.4
Women	39.9	38.5
Low HDL-cholesterol and high triglycerides (%)
Men	21.2	26.3
Women	24.9	26.9

Notes: Low HDL-cholesterol: <1.03 mmol/L (men), <1.29 mmol/L (women); high triglycerides: >1.69 mmol/L (men and women).

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).

Table 2 Effects of Niaspan^® on lipoprotein (a) (Lp(a)) in controlled clinical trials

Study	Duration (weeks)	Target dose of Niaspan^® (mg)	Mean change in Lp(a) (%)
			Niaspan^®	Comparator
Morgan et al 1996	12	2000	−27†	0 (placebo)
Knopp et al 1998	16	1500	−24.7^*	2.2 (placebo)
Grundy et al 2002	16	1500	−12	3 (placebo)
Bays et al 2003	16	2000	−21^a,*	0 (atorvastatin)
				−2 (simvastatin)
Grundy et al 2004	20	1500	−21^*	−6 (fenofibrate)
McKenney et al 2006	12	1000	−7^b,*	8 (simvastatin + ezetimibe)
			−5^c,*	11 (rosuvastatin)

Notes:Studies evaluating Niaspan^® at target doses within its therapeutic dose range (2000 mg/day) are shown. Where more than one dose was evaluated, the largest effect on Lp(a) is shown. Significant (p < 0.05 or better) vs ^*comparator or ^†baseline. Some trials involved combination of Niaspan^® with ^asimvastatin, ^batorvastatin, or ^crosuvastatin. Significance in the study of McKenney et al (2006) refers to an ANOVA across all four treatments (Niaspan^® + atorvastatin, Niaspan^® + rosuvastatin, simvastatin + ezetimibe, and rosuvastatin monotherapy).

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, b, c, d.

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.

Table 3 Effects of Niaspan^® on atherosclerosis in the ARBITER 2 study and in a pooled analysis of data from the ARBITER 2 and ARBITER 3 studies

	Niaspan^®		Placebo
	Mean change in CIMT (mm)	P	Mean change in CIMT (mm)	P
ARBITER2	0.014 ± 0.011	0.23	0.044 ± 0.011	<0.001
ARBITER 3
Patients switching from placebo to Niaspan^® (n = 47)	−0.095 ± 0.019	<0.001	–	–
Patients continuing on Niaspan^® for additional 12 months (n = 57)	−0.041 + 0.021	0.001	–	–
Pooled analysis of ARBITER 2 and ARBITER 3
First 12 months of Niaspan^® in ARBITER 2 or ARBITER 3 (n = 125)	−0.027 ± 0.011	<0.001	–	–
12–24 months of Niaspan^® in patients with type 2 diabetes or the metabolic syndrome (n = 62)	−0.046 ± 0.131	<0.001	–	–

Notes: Significance values for ARBITER 2 are relative to baseline, while significance values for ARBITER 3 or the pooled analysis of ARBITER 2 and ARBITER 3 are relative to the placebo phase of ARBITER 2. Compiled from data presented by Taylor et al (2004, ²⁰⁰⁶).

Abbreviations: CIMT, carotid intima-media thickness.

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