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


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.


METHODS
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 (beta = -0.25; p = 0.001).


CONCLUSIONS
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.
Taylor
Allen J
AJ
Cardiology Service, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA. allen.taylor@na.amedd.army.mil
Lee
Hyun J
HJ
Sullenberger
Lance E
LE
D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008076:Cholesterol, HDL / Q000097:blood; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography
D008076:Cholesterol, HDL; D003692:Delayed-Action Preparations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009525:Niacin