The SLIM Study: Slo-Niacin® and Atorvastatin Treatment of Lipoproteins and Inflammatory Markers in Combined Hyperlipidemia

Abstract

BACKGROUND: The combination of niacin and statin has proven value in hyperlipidemia management and heart disease prevention. However, the efficacy of the non-prescription time-release niacin, Slo-Niacin®, is little studied alone and not at all with atorvastatin. We gave Slo-Niacin® and atorvastatin, singly and together to determine efficacy on the combined abnormalities of triglyceride, LDL and HDL. METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or 55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or incremental doses of Slo-Niacin® to 1500 mg/day. The alternate drug was added in the next 3-month segment. Lipid profiles and transaminases were measured monthly and other measures at baseline and the end of each treatment sequence. RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin® decreased median triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%. Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36% and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I 5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin® treatment alone compared to atorvastatin and also decreased when Slo-Niacin® was added to atorvastatin. Six subjects dropped out, 3 for niacin related symptoms. CONCLUSIONS: Slo-Niacin® 1.5g/day with atorvastatin 10 mg/day improved lipoprotein lipids, apoproteins and inflammation markers without hepatotoxicity. Slo-Niacin® deserves further study as a cost-effective treatment of hyperlipidemia.

Figure 1

Randomization scheme for the order for drug administration with the monthly dose escalation of Slo-Niacin.

Figure 2

Depiction of the numbers of subjects consented, randomized and completed.

Figure 3

Percentage changes in lipoprotein levels from baseline on monotherapy (Week 12) and combined Therapy (Week 24). Primary end points are % change in LDL-C in single and combined drug treatment. ●--● Atorvastatin + Slo-niacin; ○- -○ Slo-Niacin + Atorvastatin *p<0.05, **p<0.01,***p<0.001

Figure 4

End of study measurements in the combined atorvastatin/Slo-Niacin and Slo-Niacin/ atorvastatin groups. The reduction in LDL-C is the primary end point. The 12.48% reduction in TNF-alpha is not significant but the concentration change between baseline and the end of combination therapy was statistically significant at 0.041 (Table 2D).

Figure 5

Serial monthly measurements of LDL, AST and ALT. ALT values are given as medians as the distribution is non-Gaussian. Monthly changes in LDL levels are shown for comparison.