The effect of 24 months of combination statin and extended-release niacin on carotid intima‐media thickness: ARBITER 3

ABSTRACT

Objective: The ARBITER 2 trial showed that extended-release niacin (ERN) when added to statin monotherapy slowed the progression of carotid atherosclerosis over 12 months. Whether longer treatment with ERN would have a greater effect on carotid intima.media thickness (CIMT) is unknown.

Research design and methods: We examined the long-term effects of ERN on high density lipoprotein (HDL-C) cholesterol and CIMT during 12.24 months treatment with ERN in ARBITER 2 participants who were either continued or were crossed over (from placebo) to ERN 1000 mg daily.

Main outcome measures: Among 149 subjects completing ARBITER 2, 130 (88%) enrolled in ARBITER 3. The prespecified primary endpoints were the within-group change in CIMT and HDL.C in patients receiving placebo for 12 months (n = 71), ERN for 12 months (comprised of subjects from ERN treatment during ARBITER 2 (n = 78) and those crossed over to ERN from placebo after ARBITER 2 (n = 47)), and ERN for 24 months spanning ARBITER 2 and 3 (n = 57). Five subjects discontinued the study due to flushing side effects. The study was completed by 104 subjects (47 crossed over from placebo; 57 with ERN continued from ARBITER 2).

Results: HDL.C increased in the ERN group from 39.5 ± 6.7 to 48.6 ± 13.3 mg/dl (p < 0.001) along with modest reductions in LDL.C and TG. Among 125 participants treated with ERN for 12 months, there was a net regression of CIMT of. 0.027 ± 0.011 mm (p < 0.001 vs. placebo). Among 57 participants treated with ERN for 24 months, there was additional significant regression of CIMT of. 0.041 ± 0.021 mm (p = 0.001 vs. placebo). Controlling for changes in LDL and triglycerides, only changes in HDL.C were independently associated with regression of CIMT (b =. 0.25; p = 0.001).

Conclusion: When added to statin therapy, ERN significantly increases HDL.C and induces atherosclerosis regression measured by CIMT over 24 months. Limitations to this study include its open-label design and the inability to relate CIMT effects to clinical outcomes.

Key words: :

• Atherosclerosis
• Clinical trials
• Lipids
• Risk factors

Notes

* Presented at the Annual Scientific Session of the American Heart Association, November 12–16, 2005, Dallas, TX, USA The opinions or assertions herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense