UPDATE 2-Niaspan tops Zetia in new setback for Merck drug

* Niaspan leads to reduction in artery wall thickness

* No meaningful change seen with Zetia

* 5 times as many serious adverse events seen with Zetia

* Journal editorials cite several limitations of study (Adds reaction, researcher, Merck, NEJM editorial comments)

By Bill Berkrot and Ransdell Pierson;

ORLANDO, Nov 15 (Reuters) - Abbott Laboratories' (ABT.N) Niaspan appeared to be more effective and safer than Merck & Co's (MRK.N) Zetia as a secondary cholesterol treatment, according to a small study released on Sunday that is likely to further tarnish Merck's damaged cholesterol franchise.

The damage, however, may be limited by the limitations of the study itself, which included data from just 208 patients and was criticized in a major medical journal.

"Niacin is the clear winner and led to very clear reductions in the amount of atherosclerosis that patients had," Alan Taylor, the study's lead investigator who will present the data on Monday at the American Heart Association scientific meeting in Orlando, Florida, said in an interview.

Atherosclerosis, which occurs when there is a build-up of dangerous plaque in the arteries, can lead to heart attacks.

Two earlier studies had led to questions about the value and effectiveness of Zetia and a related Merck drug, Vytorin, after which sales of the medicines plunged, although it remains a $4 billion a year franchise.

Analysts have said another negative study on Zetia, Merck's brand name for ezetimibe, could slash sales by a further 25 percent or more depending on how prescribing physicians react to the data.

"This trial doesn't quite put the nail in the coffin for ezetimibe, but it pushes it way down on the list of medications for cholesterol-lowering therapy," Anthony DeMaria, editor-in-chief of the Journal of the American College of Cardiology, said in a statement.

The study tested the effect on carotid artery wall thickness of adding either Niaspan, a long-acting niacin that raises good HDL cholesterol, or Zetia, which lowers bad LDL levels. It involved patients who had heart disease or high risk of heart disease whose LDL was already at target levels from taking statins -- the first-line treatment for high cholesterol -- but who had low HDL levels.

Increases in thickness of the artery wall could be an indicator of build-up of dangerous plaque that causes atherosclerosis and can lead to heart attacks, while a decrease could indicate regression of the disease.

The 14-month, 363-subject study sought to determine whether a patient on statins in need of additional therapy would benefit more from further driving LDL down or raising HDL. "This is a question that clinicians are faced with every single day," Taylor explained.

Even though the study was halted early, with 14-month data available for only 208 patients, "Niaspan turned out to be clearly superior to ezetimibe," Taylor said

Niaspan patients had an average reduction in carotid artery wall thickness -- known as intima-media thickness -- of 0.014 millimeters compared with no real change in the Zetia group.

Perhaps of more concern was the five times difference in major adverse events, defined as heart attack, death from heart disease, need for artery-clearing procedures or hospitalization for acute coronary syndrome, although the numbers were small.

There were nine major adverse events in the Zetia group of patients, or 5 percent, compared with two with Niaspan, or 1 percent.

Taylor recommended that doctors refrain from using Zetia in patients until data become available that show it definitively prevents heart attacks and strokes. Merck is currently conducting a large study it hopes will prove just that.

"To assume that a drug is OK just because LDL goes down is no longer an assumption you can make," Taylor said.

But a pair of editorials in the New England Journal of Medicine questioned the study and its conclusions.

"Unfortunately, the premature termination of the trial, the small number of patients studied and the limited duration of follow-up preclude us from conclusively declaring niacin the adjunctive agent of choice," one editorial concluded, adding that the result "does not necessarily merit changes in our lipid-lowering guidelines at this time."

A second editorial said not including data from all 363 patients was a missed opportunity to enhance the study's precision.

Despite the study's "several limitations," it said "the primary results are likely to be correct, although the magnitude of the difference between the treatment arms may be overestimated."

Taylor said he observed an apparent paradox in that Zetia patients who experienced the greatest LDL reduction had an increase in artery wall thickness. "These data suggests that something mechanistically is wrong with ezetimibe," he said.

But Merck research chief Peter Kim defended his company's drug, calling Taylor's study, "scientifically inadequate."

"It would be inappropriate in my opinion for physicians to be taking (this) data and making any changes in their clinical practice with regard to these drugs. It would not be good for public health," Kim said. (Editing by Leslie Adler)