Niaspan vs Zetia: Analysts Don't Hedge Their Bets

According to yesterday's WSJ, stock analysts are speculating that Abbott's extended-release niacin (Niaspan) outperformed ezetimibe (Zetia; Merck/Schering-Plough) in a phase 4 head-to-head atherosclerosis study that was terminated early in June. The NIH clinical-trials web site indicates that an independent steering committee stopped the trial on the basis of results from a prespecified, blinded interim analysis and adds that the study was not stopped because of safety concerns.

The principal investigators are otherwise mum, advising that the trial results will be presented in mid-November at the Scientific Sessions of the American Heart Association. But the logical conclusion is that one drug significantly outperformed the other; stock analysts are placing their bets on Niaspan, possibly because the study is cosponsored by Abbott.*

The randomized, open-label, 2-center study, abbreviated ARBITER 6-HALTS, was designed to compare the effects of raising the HDL level (with Niaspan) with those of lowering the LDL level (with Zetia) at 14 months. The primary endpoint, as in the notorious ENHANCE study, was the mean change in the intima-media thickness of the common carotid artery (CIMT). (Presumably all enrollees received statin therapy; so Niaspan and Zetia were add-on medications.)

It's important to note that the NCEP ATP III guidelines stress the lowering of the LDL level as the primary target of cholesterol-altering therapy. Therefore Abbott has a vested interest (and an uphill battle) in showing that raising the HDL level with Niaspan is just as good as, or possibly better than, lowering the LDL level with Zetia. In a previous, placebo-controlled study, ARBITER 2 (N = 167), Niaspan reduced the rate of CIMT progression when added to statin therapy in high-risk patients who did not have insulin resistance; however, the drug did not appear to alter the risk of cardiovascular events at 1 year.

Unlike ARBITER 6-HALTS, ARBITER 2 was placebo controlled, and study drugs were assigned in a double-blind fashion. A drawback of both trials is the fact that the primary endpoint, the mean change in CIMT, is merely a surrogate marker for clinical cardiovascular outcomes.

ARBITER 6-HALTS = ARterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 - HDL and LDL Treatment Strategies in Atherosclerosis; ENHANCE = Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression; HDL = high-density lipoprotein; LDL = low-density lipoprotein; NCEP ATP III = Third Adult Treatment Panel of the National Cholesterol Education Program.

* The other cosponsor is the Walter Reed Army Medical Center.