An experimental drug that greatly increases levels of "good" cholesterol has no effect on heart health, a comprehensive clinical trial found, leaving researchers shocked and disappointed.
It is also a blow to patients who were hoping for an alternative because they cannot or will not take statins, which can cut low-density lipoprotein (LDL), or bad cholesterol.
The study involving more than 12,000 patients at high risk for serious cardiovascular problems found that the drug evacetrapib had no benefits, according to research presented Sunday at the American College of Cardiology conference in Chicago.
Manufacturer Eli Lilly stopped the trial in October when the drug was found to be ineffective. But now experts have given a comprehensive explanation of what happened.
Two other drugs in the same class as evacetrapib, known as CETP inhibitors and designed to raise levels of HDL cholesterol -- high-density lipoprotein, the "good" type -- have also failed, presenting experts with a quandary.
- 'Disappointed and surprised' -
"We have a paradox: here we've got an agent that more than doubles the levels of good cholesterol and lowers bad cholesterol and yet has no effect on clinical events," said lead author Professor Stephen Nicholls.
"We were disappointed and surprised by the results," added Nicholls, of The University of Adelaide in Australia and cardiologist at Royal Adelaide Hospital.
On average, patients taking evacetrapib daily for at least 18 months lowered their LDL cholesterol by 37 percent and increased their HDL cholesterol -- high-density lipoprotein, the "good" type -- by 130 percent compared with patients taking a placebo.
However, there was no difference between the two groups in terms of the primary "endpoint" of the research -- including the amount of time until cardiovascular death, heart attack, stroke or coronary artery bypass surgery.
"As we close out the trial, we're trying to understand how a drug that seems to do all the right things in terms of blood cholesterol levels doesn't then translate into reducing clinical events," added Nicholls.
Steve Nissen, chairman of Cardiovascular Medicine at Cleveland Clinic, attempted to put a positive spin on the disappointing outcome.
"These findings illustrate the importance of performing large, high-quality outcome trials," he said.
"Just looking at the effects a therapy has on cholesterol levels doesn't always translate into clinical benefits."
However, Nicholls cautioned that evacetrapib could potentially benefit patients with low risk of serious heart trouble, although that was not part of the study.
The findings could challenge conventional thinking regarding the benefits of HDL cholesterol in protecting against cardiovascular problems, he said.
They also suggest that existing treatments, such as statins, are already so effective that they cannot be improved upon.
- Side effect woes -
However, some people with high cholesterol are hoping for an alternative to statins because they complain about side effects such as muscle pain and weakness.
They have high hopes for a new drug like Repatha, produced by the US company Amgen or its rival Praluent, sold by the French firm Sanofi with its American partner Regeneron.
The two new powerful anti-cholesterol drugs of the same class were approved last year by the Food and Drug Administration only to patients with a hereditary form of high bad cholesterol and those with cardiovascular disease but not for prevention.
These new anti-cholesterol drugs don't cause side effects on muscles in most people, according to a recent clinical trial. But they are very expensive, costing around 14,000 dollars a year.