Final ARBITER 6-HALTS analysis indicated improved CIMT with extended-release niacin

The use of extended-release niacin in patients with known coronary heart disease was associated with greater reductions in carotid intima-media thickness than ezetimibe therapy, final results of the ARBITER 6-HALTS trial suggested.

Researchers from several U.S. sites included 363 patients with known CHD or CVD who were currently assigned to statins. Patients’ LDL was <100 mg/dL, and HDL was <50 mg/dL for men and <55 mg/dL for women. They were randomly assigned to extended-release niacin at 2,000 mg per day or ezetimibe at 10 mg per day, with a primary study endpoint of change in carotid intima-media thickness (CIMT).

According to the final analysis of 315 patients, there was a reduction in mean CIMT (–0.0102 ± 0.0026 mm; P<.001) and maximal CIMT (–0.0124 ± 0.0036 mm; P=.001) in patients assigned to extended-release niacin when compared with baseline. Patients assigned to ezetimibe had no reduction in mean CIMT (–0.0016 ± 0.0024 mm; P=.88) or in maximal CIMT (–0.0005 ± 0.0029 mm; P=.88) vs. baseline. The researchers also reported a difference between the two groups for the mean changes in CIMT, favoring niacin for mean (P=.016) and maximal CIMT (P=.01).

“Final results from the ARBITER 6-HALTS trial confirm the superiority of extended-release niacin over ezetimibe for the endpoint of change in CIMT and the ability of niacin to induce CIMT regression,” the researchers concluded. “Increased cumulative drug exposure was related to regression of CIMT with niacin and progression of CIMT with ezetimibe.” – by Eric Raible

Villines TC. J Am Coll Cardiol. 2010;doi:10.1016/j.jacc.2010.03.017.

This new analysis of the final results of the HALTS trial is very consistent with the original article. By using the last observation carried forward analysis, the investigators significantly increased their number of data points, and their results are even more compelling now. It is clear that in this study high-dose extended-release niacin improved CIMT whereas ezetimibe did not.

Since we do not have clinical outcome data with ezetimibe, most clinicians will likely make niacin their preferred second-line lipid- lowering agent after a statin. Fenofibrate will probably be considered as a potential third-line agent for those with triglyceride levels >200 and a low HDL, based on the recent ACCORD results. Ezetimibe and colesevelam (Welchol, Daiichi Sankyo) are other potential third-line agents for individuals who cannot reach their target LDL or non-HDL goals despite use of a maximally tolerated dose of a potent statin.

It is likely that clinical guidelines for lipid-lowering will not change a great deal until the results of the two main niacin clinical trials (AIM-HIGH and HPS2-THRIVE) are completed. If the results of one of these clinical trials show a benefit of niacin on top of statin therapy, HALTS will go down as a landmark preventive cardiology imaging study. The investigators should be congratulated for their carefully done, rigorous trial.

– Roger Blumenthal, MD
Cardiology Today Section Editor

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