People with high levels of the so-called good cholesterol HDL tend to have fewer heart attacks but HDL may offer little protective benefit in people who take statins to lower harmful LDL cholesterol, U.S. researchers said on Wednesday.

An analysis of a large study of healthy people who took AstraZeneca’s statin drug Crestor to prevent heart attacks found having high HDL was not a good predictor of heart attack risk.

“HDL is a very powerful predictor of future risk” of heart disease, said Paul Ridker of Brigham and Women’s Hospital in Boston, whose study appears in the journal Lancet.

But “once we get LDL into these very low ranges with very potent statins, HDL no longer predicts future risk of heart disease,” he said in a telephone interview.

The findings raise questions about drugs in development to raise HDL to prevent heart attacks, he said.

Several companies are working on HDL-raising drugs, which would likely be combined with statins in hopes of developing even more potent weapons against heart disease.

Tiny Canadian biotech ResVerlogix has an experimental drug in clinical trials that increases production ApoA-1 in the blood, which then raises HDL - a compound that helps ferry harmful fats out of the blood.

Raising HDL through increased ApoA-1 is a different approach from other HDL boosters, such as a class known as CETP inhibitors that included torcetrapib, Pfizer’s most spectacular clinical failure. Merck & Co and Roche are still developing CETP inhibitors.

Current drugs that raise natural levels of HDL, such as niacin, cause unpleasant side effects such as flushing.

NO DIFFERENCE

In the original study, called JUPITER, patients with average to low levels of low-density lipoprotein or LDL were given Crestor or rosuvastatin, which cut their bad cholesterol concentrations to levels seen in Aboriginal populations but rarely seen in Western patients.

People in the study who took Crestor had 54 percent fewer heart attacks and 48 percent fewer strokes after two years compared with people who took a placebo.

In the new analysis, Ridker and colleagues looked to see if HDL was still a predictor of heart attack risk in people who took Crestor.

They found that HDL was still protective in people who got the placebo, but in those whose cholesterol was lowered by the statin, having high HDL made no difference in predicting which patients would have heart problems.

The findings suggest higher HDL concentrations may not be a good measure of heart risk in people who lower their bad cholesterol levels with statins, Dr. Derek Hausenloy of The Hatter Cardiovascular Institute at University College London said in a commentary.

“Whether increasing HDL cholesterol in patients with very low LDL cholesterol has any beneficial effects on cardiovascular risk remains to be shown directly in large randomized trials,” he said.

Ridker agrees.

“In my heart of hearts, I believe the only way to address whether or not new agents that increase HDL will be effective is through well-done carefully taken out clinical trials. There is no other way to get there,” he said.

SOURCE:  The Lancet, online July 22, 2010.