A New Way to Raise ‘Good’ Cholesterol?

Meeting the challenge of increasing HDL

Drugs to reduce LDL, the “bad” cholesterol, have been around for decades. Until recently, though, researchers were puzzled by how to increase HDL, the “good” cholesterol.

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A new drug under trial may help play a role in raising good cholesterol in the not-too-distant future.

What is cholesterol?

Cholesterol is a waxy substance found in every cell of the human body. It’s used to produce hormones and vitamin D, and it aids in digestion. Because the body produces all the cholesterol it needs, the additional cholesterol found in many foods is unnecessary.

Cholesterol is carried through the bloodstream in two kinds of lipoproteins: low-density (LDL) and high-density (HDL). It’s important to have healthy levels of both types.

HDL carries excess cholesterol to the liver, where it’s removed from the body. If, however, LDL cholesterol levels are too high beyond the ability of HDL to clear it, cholesterol can build up in the arteries. And too much cholesterol in the arteries can cause arteriosclerosis, a thickening of the arterial walls, which leads to reduced blood flow to the heart and brain and increases the risk of heart attack and stroke.

You can raise HDL cholesterol levels by incorporating healthy dietary and lifestyle changes, such as quitting smoking, eating less red meat and dairy products and exercising more.

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A promising new drug

Now a new drug, evacetrapib, shows promise in raising HDL.

Leading a study of evacetrapib is Stephen J. Nicholls, MBBS, PhD. Dr. Nicholls is beginning a Cleveland Clinic-led phase 3 clinical trial of the drug. The worldwide study involves over 11,000 patients in more than 30 countries.

“We’re moving forward to assess whether the medication reduces the likelihood that patients will have heart attacks and strokes,” Dr. Nicholls says.

Previous studies of several other drugs reported raised HDL levels in trial participants, but were stopped after researchers discovered associated health risks and a failure to reduce heart attack risk. In contrast, Dr. Nicholls says that early studies of evacetrapib showed no major side effects.

“We’re not really sure why it’s proving more difficult to increase HDL,” says Dr. Nicholls. “Decreasing LDL seems to be pretty straightforward. Medications that lower LDL typically reduce clinical events. Medications that raise HDL have variable effects on clinical events, and several have failed to protect in recent large trials. It may be that the way HDL is raised is particularly important.”

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How the new drug works

Evacetrapib works by blocking a factor that normally allows transfer of cholesterol from the good form to the bad. As a result, the good form of cholesterol is raised, and the bad form is lowered. “We’d like to think that should be good for patients in terms of less risk of heart attack and stroke,” Dr. Nicholls says.

“Although preliminary studies are encouraging, the current clinical trial will take another three to four years,” says Dr. Nicholls. “Outcomes will then be studied and evaluated before the drug might be approved.”

Stephen J. Nicholls, MBBS, PhD, Medical Director of Intravascular Ultrasound and Angiography Core Laboratories and Clinical Director of the Center for Cardiovascular Diagnostics and Prevention at Cleveland Clinic. Currently in Australia as Professor of Cardiology at the South Australian Health & Medical Research Institute, Dr. Nicholls is beginning a phase 3 clinical trial of the drug, led by Cleveland Clinic.

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