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Drug may boost good cholesterol

An experimental drug can dramatically boost levels of HDL, the good cholesterol, potentially offering an entirely new way to prevent heart attacks.

In a preliminary study, researchers at University of Pennsylvania and Tufts University found that the drug doubled HDL in people with worrisomely low levels of the heart-healthy substance. The drug, called torcetrapib, also reduced LDL, the bad cholesterol.

Good cholesterol reduces the risk of heart disease; bad cholesterol raises it.

Until now, doctors have concentrated largely on lowering bad cholesterol by giving patients statin drugs, which are used by millions of Americans and reduce heart attacks by about one-third. Many experts hope to drive down heart disease still further by boosting good cholesterol, too, and several strategies are in testing.

The latest study was small, involving 19 patients, but its striking results suggest torcetrapib can have a powerful effect.

The drug is still a few years away from reaching the market. The next step will be to test its safety and effectiveness in much larger numbers of volunteers.

"One of the big questions that we do have with this drug is: Will using it to raise HDL levels from normal to high actually reduce risk in people who are at high risk?" said the study's senior author, Dr. Daniel Rader, Penn's director of preventive cardiovascular medicine.

Ultimately, the drug could be used in combination with statins to simultaneously lower a patient's bad cholesterol and boost good cholesterol.

The study, paid for in part by Pfizer Inc., torcetrapib's maker, was published in today's New England Journal of Medicine.

The only HDL-raiser on the market is the vitamin niacin, but its effects are modest, and side effects, such as itching and hot flashes, bother many patients.

Whether torcetrapib will prove to be the first potent prescription drug in this category will require much more study.

In the next stages of testing, patients will have to be followed for several years to spot side effects and prove the cholesterol changes result in fewer heart attacks for people with such risk factors as obesity, diabetes, smoking, and lack of exercise.

LDL particles -- clusters of cholesterol molecules surrounded by proteins -- act like big boats, transporting cholesterol from the liver and depositing it in blood vessels, where it can cause deadly clogs. In contrast, HDL particles pick up cholesterol in the blood vessels and shuttle it back to the liver for excretion.

Torcetrapib blocks the activity of a protein that acts like a ferry to transfer cholesterol from the HDL boat into the LDL boat. As a result, HDL levels rise and LDL levels fall.

The 19 patients took a 120-milligram torcetrapib pill daily for four weeks; 10 also took the statin Lipitor every day.

HDL levels rose an average of 46 percent in those taking torcetrapib, to 46 milligrams per deciliter, and jumped 61 percent, to 47, in those getting both medicines. Six patients took torcetrapib twice a day in the study's third phase, and their HDL jumped to 70.

In the United States, men's average HDL is about 45 and women's is 55. HDL under 40 is an especially bad sign, while anything over 60 is considered good. Studies suggest that each single point of increase in HDL is matched by a 2 percent to 3 percent reduction in heart disease.

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