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Huge drug trial turns up unexpected cholesterol win

Health & Medical

A FAILED heart disease drug has surprised researchers by proving its ability to lower levels of “bad” cholesterol and boost the “good”.

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South Australian Health and Medical Research Institute (SAHMRI) Deputy Director and Heart Health Theme Leader Professor Stephen Nicholls led the 12,000 participant ACCELERATE trial in conjunction with Dr Steve Nissen and Dr A Michael Lincoff at the Cleveland Clinic Coordinating Center for Clinical Research.

ACCELERATE, the phase 3, multi-centre clinical trial of the drug evacetrapib failed to reduce rates of major cardiovascular events, including heart attack, stroke, angina or cardiovascular death.

However, the drug reduced levels of low-density lipoprotein (LDL, or “bad” cholesterol) by 37 per cent while raising levels of HDL (“good cholesterol”) by 130 per cent.

The trial involved 540 sites and more than 12,000 patients who were at high risk of serious cardiovascular problems. They were randomized to receive either 130 milligrams of evacetrapib or a placebo daily, along with standard medical therapy throughout the trial. 

Participants in the study had experienced some forms of cardiovascular problems within a year of enrolling. 

Researchers observed a borderline significant reduction in all-cause mortality in the evacetrapib group; however, that was not driven by a decrease in cardiovascular death. 

Prof Nicholls, who is also Professor of Cardiology at the University of Adelaide, presented the trial findings in the United States on April 3. 

He said the findings are also being presented at a major scientific meeting of the American College of Cardiology in Chicago and were another excellent example of SAHMRI research being presented on the global stage.


“SAHMRI is playing a major role in the leadership of these trials. It’s an important sign of how we are building the capacity to perform high quality clinical research in South Australia.”

SAHMRI opened in late 2013 and is in the new Adelaide BioMed City precinct, a $3 billion tripartite health hub comprising a soon-to-be-completed major hospital, research centres and educational institutions.

ACCELERATE was discontinued in October 2015, on the recommendation of the independent Data Monitoring Committee after preliminary data suggested the study would not meet its primary endpoint of a reduction in major cardiovascular events. 

Evacetrapib is in a class of drugs known as cholesteryl ester transfer protein (CETP) inhibitors. They work by disrupting the process that normally transfers cholesterol from HDL cholesterol to LDL cholesterol in the body. 

High levels of LDL cholesterol in the blood have been linked to coronary heart disease.

Animal and genetic studies have suggested that CETP deficiency is cardioprotective; however, this is the third failure in this class of drugs.

This is a Creative Commons story from The Lead South Australia, a news service providing stories about innovation in South Australia. Please feel free to use the story in any form of media. The story sources are linked in with the copy and all contacts are willing to talk further about the story. Copied to Clipboard

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