Evidence against raising “good” cholesterol with drugs.

Doctors and drug companies don’t like to report negative results, but when it comes to medications that raise HDL, or good cholesterol levels, they’re getting used it.

In a presentation at the American College of Cardiology, researchers report that the latest study involving such a drug, made by Eli Lilly, didn’t seem to reduce heart disease events.

The study involved an experimental drug called evacetrapib, the third drug of its class designed to raise HDL levels. In studies, people with higher HDL levels tend to have lower rates of heart disease; exercise also raises HDL, and heart doctors believe that HDL can counteract the build-up of harmful cholesterol in heart vessels.

More than 12,000 people at high risk of heart disease—most of whom were overweight or obese, had high blood pressure, had diabetes or had experienced a heart event—were randomly assigned to take evacetrapib or placebo and were followed for 1.5 years. The drug significantly increased HDL levels in people who took it, by about 130%, and lowered LDL by 37%. But a year after starting the drug, there was little difference in the number of heart events between the two groups. That prompted the company and the researchers conducting the trial to stop the study early. Lilly also decided to stop developing the drug.

“This drug did all the right things to lipids but didn’t do anything to morbidity and mortality from heart disease,” says Dr. Steven Nissen, chair of cardiovascular medicine at the Cleveland Clinic and chair of the steering committee for the study.

MORE: A Common Cholesterol Drug’s Safety Is In Question

That means that “it really does matter how you lower LDL,” he says. Statins and likely the latest class of cholesterol lowering drugs, the PCSK9 inhibitors, work on the liver by boosting activity of the LDL receptors on the liver, which results in less LDL circulating in the blood. Evacetrapib works through a different pathway by making less LDL and building up more HDL.

But how could a drug that lowered LDL and boosted HDL have such little effect on the heart? Nissen says it’s still not clear how evacetrapib affects cholesterol particles, but it’s possible that since LDL comes in different forms (some which are more damaging to the heart than others) evacetrapib may be pushing production of the more harmful type. Even with lower levels of LDL, there may still be sufficient blockage of heart vessels. The end result is no reduction in the risk of heart events.

“In my opinion it’s now three strikes against this class of drugs,” says Nissen. “It’s time to move on.” But other pharmaceutical companies are still developing drugs to increase HDL levels in the hopes that this pathway will prove helpful for the heart. Time (and more research) will tell if their formulations are different enough to have an effect.

http://time.com/4279691/hdl-cholesterol-drugs-heart/

 

2 Responses

  1. Paul Littlefield says:

    My goodness, these are perplexing results. I wonder what on earth could be going on. Could it be possible that the vaunted association between cholesterol levels and cardiovascular disease is merely an association, with no causal effect involved? How could that possibly be?

    Of course we know with equal certainty that margarine consumption correlates with the divorce rate in the state of Maine, so . . . .

    • Richard Feinman says:

      Thanks for your comments but there is also the possibility that the association between cholesterol and CVD is not a meaningful relationship at all, that is, is a consequence of the poor methodology in analysis of different data studies. I don’t think we know the causes of heart disease but to be safe, I avoid margarine and have not been in Maine in several years. We are just getting this site together and expect to address the question further.

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