Melbourne | A drug used to lower bad cholesterol and increase good cholesterol does not reduce rates of major adverse cardiovascular events, a new global study has found.
The favourable effects of the drug evacetrapib on cholesterol did not translate into any reduction in the study’s primary endpoint – cardiovascular death, heart attack, stroke, coronary artery bypass surgery or hospitalisation for chest pain due to unstable angina, a restriction in the flow of blood through the heart’s arteries, researchers said. Here we have got an agent that more than doubles the levels of good cholesterol and lowers bad cholesterol and yet has no effect on clinical events.
We were disappointed and surprised by the results, said Stephen Nicholls from University of Adelaide in Australia. The study was a phase 3, randomised, double-blind trial conducted in approximately 540 global health centres involving more than 12,000 patients at high risk for serious cardiovascular problems.
Participants were randomised to receive either 130 milligrams of evacetrapib or a placebo daily for at least 18 months. All patients also received standard medical therapy throughout the trial, which in a vast majority of cases included treatment with statins or other cholesterol-lowering drugs, researchers said.
On average, patients taking evacetrapib lowered their low-density lipoprotein (LDL) cholesterol by 37 per cent and increased their high-density lipoprotein (HDL) cholesterol by 130 per cent compared with patients taking a placebo, they said. However, there was no difference between the two groups in terms of the study’s primary endpoint.
The findings make evacetrapib the third failure in a class of drugs known as cholesteryl ester transfer protein (CETP) inhibitors, which are designed to disrupt the natural process by which HDL cholesterol is converted into LDL cholesterol in the body, researchers said.
There has been, and continues to be, a lot of confusion about what is going on with this class of drugs, since we do not yet have one that can be brought to the clinic to prevent heart attack and stroke in our patients, said Nicholls. One possible explanation is that existing treatments, such as statins, are already so effective at improving cardiovascular outcomes that it has become more difficult to further improve outcomes in high-risk patients, researchers suggest.
We tested the drug in high-risk patients because they are the patients with the greatest need for new drugs above and beyond what we already use in our clinics, said Nicholls.