Drug trial turns up unexpected cholesterol win
A failed heart disease drug surprises researchers by proving its ability to lower levels of 'bad' cholesterol and boost the 'good'
Accelerate, a Phase III, multi-centre clinical trial of the drug evacetrapib failed to reduce rates of major cardiovascular events, including heart attack, stroke, angina or cardiovascular death.
But the researchers found that it reduced levels of low-density lipoprotein (LDL, or 'bad' cholesterol) by 37% while raising levels of HDL ('good' cholesterol) by 130%.
The trial, led by South Australian Health and Medical Research Institute (SAHMRI) Deputy Director and Heart Health Theme Leader, Professor Stephen Nicholls, in conjunction with Dr Steve Nissen and Dr A Michael Lincoff at the Cleveland Clinic Coordinating Center for Clinical Research, involved 540 sites and more than 12,000 patients who were at high risk of serious cardiovascular problems. They were randomised to receive either 130mg 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.
The researchers observed a borderline significant reduction in all-cause mortality in the evacetrapib group; however, this was not driven by a decrease in cardiovascular death.
Nicholls, who is also Professor of Cardiology at the University of Adelaide, presented the trial findings in the US on 3 April.
'We only make these discoveries by performing large clinical trials, which enrol more than 10,000 patients in up to 40 countries around the world,' he said.
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.
