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

• Published in: Current medical research and opinion Vol. 22; no. 11; pp. 2243 - 2250
• Main Authors: Taylor, Allen J., Lee, Hyun J., Sullenberger, Lance E.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.11.2006; Taylor & Francis; Informa Healthcare
• Subjects: Aged; Atherosclerosis; Carotid Arteries - diagnostic imaging; Carotid Artery Diseases - blood; Carotid Artery Diseases - diagnostic imaging; Carotid Artery Diseases - drug therapy; Cholesterol, HDL - blood; Clinical trials; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Intracranial Arteriosclerosis - blood; Intracranial Arteriosclerosis - diagnostic imaging; Intracranial Arteriosclerosis - drug therapy; Lipids; Male; Middle Aged; Niacin - administration & dosage; Niacin - therapeutic use; Risk factors; Treatment Outcome; Tunica Intima - diagnostic imaging; Tunica Media - diagnostic imaging; Ultrasonography
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/030079906X148508

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.