UPDATE 1-Serious side effects seen with failed Merck niacin drug

Sat Mar 9, 2013 4:05pm EST

By Bill Berkrot

SAN FRANCISCO, March 9 (Reuters) - Unexpected serious side effects arose in a huge study of a Merck & Co long-acting niacin drug aimed at raising good HDL cholesterol, according to data released on Saturday, possibly adding another nail to the coffin of niacin therapy for heart patients.

Merck has already given up on the drug that combines extended-release niacin with an experimental agent called laropiprant, designed to prevent the uncomfortable facial flushing associated with niacin.

When it was announced that the drug called Tredaptive had failed to prevent heart attacks, strokes, death and other complications in heart patients also taking drugs to lower bad LDL cholesterol, Merck said it would not seek U.S. approval and would stop selling it in the dozens of other countries where it was already available.

A European medical journal last week said the drug caused concerning muscle weakness, especially in Asian patients.

But the results presented on Saturday at the American College of Cardiology scientific meeting in San Francisco painted an even more troubling picture of the medicine.

Researchers found patients taking the Merck drug had significantly higher rates of bleeding - 2.5 percent vs 1.9 percent - and infections - 8.0 percent vs 6.6 percent - that they called unexpected.

Significantly higher numbers of patients taking Tredaptive also experienced serious health problems that researchers called known side effects of niacin. Those included new onset diabetes - 9.1 percent vs 7.3 percent - diabetic complications - 11.1 percent vs 7.5 percent - and gastrointestinal problems - 4.8 percent vs 3.8 percent.

Niacin, a form of vitamin B, has been used for many years in the belief that its HDL raising powers would help prevent heart attacks and strokes.

Professor Jane Armitage, who led the study called HPS2-Thrive, called the findings disappointing.

"Still," she said, "finding out a drug is not helping people is just as important as finding that it has benefits."

But Dr. Steven Nissen, head of cardiology at Cleveland Clinic, had some serious criticism about the study's design, execution and conclusions, and was not prepared to write off niacin therapy just yet for patients with very low HDL levels.

"Sometimes large and simple trials are large and sloppy trials," he said.

Among his concerns Nissen cited the very large number of Asians in the study that could have skewed the results because Asians tend to not tolerate high dose niacin. Nissen also said the baseline LDL levels of 66 for patients in the study were unrealistically low and that those with higher LDL levels may have benefited from the drug.

The trial was not designed to show whether the adverse side effects were caused by the niacin or the anti-flushing drug, another potential failing.

But Armitage, a professor at the University of Oxford, said the results were consistent with an earlier failed niacin study that did not include laropiprant and that many of the side effects are known to be associated with niacin.

"We now know that its adverse side effects outweigh the benefits when used with current treatments," she said.

Nissen was not so sure, saying this was not the final nail in the niacin therapy coffin.

"There are some nails in the coffin. But it doesn't absolutely answer the question," he said of the study. "I don't know that it was the niacin. They may be right, but they may be wrong."