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Drug shows promise in boosting 'good' cholesterol

A clinical study of the new drug anacetrapib shows a dramatic increase in HDL cholesterol levels, seen as a key to lowering heart disease risk, without the side effects seen in a previous drug.

November 17, 2010|By Shari Roan, Los Angeles Times

A medication under development dramatically raises good cholesterol, reduces bad cholesterol and, so far, appears safe, researchers reported Wednesday.

The study, published in the New England Journal of Medicine, is a key step toward development of a drug that boosts HDL cholesterol. Studies have shown that people who have naturally high HDL levels are at lower risk for heart disease, and cardiologists have long sought a strategy to raise HDL cholesterol in those whose levels are low.

The goal has not been easy, however. A previous drug intended to do the same thing was yanked from the research pipeline in 2006 because of dangerous side effects.

The new drug under investigation, anacetrapib, was tested in a trial of 1,623 adults who were already taking statins, medications that lower so-called bad, or LDL, cholesterol because they had heart disease or were at high risk of developing heart disease. The patients were randomized to also receive either 100 milligrams of anacetrapib or a placebo for 18 months.

Anacetrapib raised HDL cholesterol from 40 to 101 milligrams per deciliter, 138% beyond the increase of 40 to 46 mg/dL found in the placebo group. HDL cholesterol levels of 60 mg/dL or higher are considered protective against heart disease.

In addition, the participants taking anacetrapib (who already had satisfactory LDL cholesterol because of statin therapy) experienced a reduction in LDL cholesterol from 81 to 45 mg/dL, 40% better than the decrease of 82 to 77 mg/dL found in the placebo group.

Optimal LDL levels are less than 100 mg/dL.

Only one other medication, niacin, or vitamin B3, is available to boost HDL cholesterol, but its effects are modest and the vitamin causes flushing and itching that is intolerable to some patients, said Dr. Christopher Cannon, senior author of the study and a cardiologist at Brigham and Women's Hospital in Boston. Cannon presented the findings Wednesday at the American Heart Assn.'s annual Scientific Sessions meeting in Chicago.

"This drug has five times more effect than niacin on raising HDL. It affords the opportunity to have a big effect," Cannon said.

It is still unknown, however, whether raising HDL with anacetrapib will result in lower rates of heart attacks, strokes and death because the study did not measure those outcomes. A 30,000-patient, international study will begin soon to answer those questions and to continue to evaluate the drug's safety. Patients in that study will be followed for four years.

"What we know with HDL cholesterol is that it's statistically associated with a decreased risk of cardiovascular disease," said Dr. John C. LaRosa, president of the State University of New York Downstate Medical Center in Brooklyn. LaRosa was not involved in the study. "It doesn't mean if we find a way of raising HDL that that translates into lower incidence of cardiovascular disease.

"If studies prove that raising HDL is beneficial and is not associated with side effects, it will be a very successful drug," LaRosa added

There are early suggestions that the drug may indeed affect people's heart health, Cannon said. Only eight patients taking anacetrapib in the study needed procedures to open blocked blood vessels, compared with 28 in the placebo group. These numbers are small and not definitive, he cautioned.

"This gives us a strong hint that this strategy may really work," he said. "We have to prove that with a big trial."

Anacetrapib has a different chemical structure than the medication abandoned in 2006, torcetrapib. However, both drugs are from a class of compounds called cholesteryl ester transfer protein inhibitors that alter cholesterol metabolism in favor of HDL cholesterol creation.

"By blocking this enzyme, you would have less LDL and more good HDL," Cannon said.

Torcetrapib increased blood pressure and resulted in more heart attacks, strokes and deaths in patients taking it, causing its manufacturer, Pzifer, to halt research on the drug. Researchers hope that anacetrapib, made by Merck and Co., is different enough to avoid the same side effects.

"If you just make a little change in the molecule, it may make a huge difference," said Dr. Thomas Luscher of University Hospital Zurich in Switzerland. Luscher was not involved in the trial.

Anacetrapib, unlike torcetrapib, did not raise blood pressure. However, in some patients the LDL cholesterol levels fell to below 25 mg/dL, considered low. These people were taken off the medication as a precaution, Cannon said. Whereas high LDL cholesterol is clearly bad, it's not known if too-low LDL levels could be harmful.

Proving safety will be of major importance in the large, international trial of anacetrapib, LaRosa said. "This study doesn't help us understand safety," he said. "It's not big enough."

shari.roan@latimes.com

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