New Drug Could Raise Good Cholesterol and Lower Bad Cholesterol

Nov. 15, 2011— -- An experimental new drug may someday offer people struggling with cholesterol problems a treatment option that raises good cholesterol and lowers bad cholesterol in the blood, potentially reducing the risk of suffering a heart attack or other cardiac problems.

Researchers from the Cleveland Clinic, Georgetown University's MedStar Research Institute, Academic Medical Center in the Netherlands and Eli Lilly examined the effects of a drug called evacetrapib on cholesterol levels in nearly 400 patients with either low HDL, the "good" cholesterol, or high LDL, the "bad" cholesterol.

The study, presented at this year's American Heart Association meeting and published in this week's Journal of the American Medical Association, found that evacetrapib, either alone or in combination with cholesterol-lowering statins, increased HDL cholesterol and lowered LDL cholesterol.

"The drug more than doubled HDL and lowered LDL by 36 percent," said Stephen Nicholls, the study's lead author and clinical director of the Cleveland Clinic Center for Cardiovascular Diagnostics and Prevention. "There was a profound effect on the protective aspect of HDL and lowered LDL in a way we see with statins. If the drug was added to statins, we saw better lowering than with statins alone."

While the results are promising, Nicholls and experts not involved in the research say they are very preliminary. Without additional long-term studies, it's unclear whether the drug will be successful in decreasing the number of deaths from heart disease or the number of cardiac "events."

"We've known from epidemiological studies that low HDL levels are associated with an increased likelihood of heart disease and heart attack, and high levels are protective," said Dr. Cam Patterson, chief of the division of cardiology at the University of North Carolina School of Medicine in Chapel Hill. Patterson was not involved in the evacetrapib research.

"The average HDL level is about 45 mg/dl, and for every one point that goes up, the risk of heart disease goes down three percent," said Dr. Philip Ragno, director of cardiovascular health and wellness at Winthrop University Hospital in Mineola, N.Y.

But it's still unclear what actual effect raising HDL levels using this drug will have on heart disease.

"We don't know what will be the effect on clinical events," said Nicholls. "That will be the major determinant of whether these drugs come into clinical practice."

Limited Options for Raising HDL

Evacetrapib belongs to the class of drugs known as cholesteryl ester transfer protein inhibitors. The first drug in this class, torcetrapib, raised HDL levels, but its clinical trial was stopped because of deaths caused by side effects of the drug.

One of the challenges with developing drugs that can raise HDL, according to Nicholls, is that HDL is very complex.

"HDL is really complicated. It comes in all shapes and sizes, and we don't know if all are equally as protective," he said. "All forms of LDL are bad and we know that if we lower all forms, good things happen to patients."

"The only other drug that we have that raises HDL is niacin. Many cardiologists have used it to raise HDL levels, and it's shown a modest increase of up to 30 percent in some individuals," said Dr. Philip Ragno, director of cardiovascular health and wellness at Winthrop University Hospital in Mineola, N.Y.

But data from the recent AIM-HIGH study, which tried to determine whether adding niacin to statin treatment regimens would raise HDL levels in people who successfully lowered their LDL with statins, showed the drug combination did not reduce the chances of having a heart attack. As a result, the AIM-HIGH trial ended a year and a half early.

Evacetrapib: The 'Holy Grail'?

In an accompanying editorial, Dr. Christopher Cannon of Brigham and Women's Hospital in Boston, said evacetrapib is one of several promising HDL-raising options currently being tested.

"Further interventions await data from the large randomized trials of current therapies (e.g., niacin) and emerging therapies like the CETP inhibitors, including dalcetrapib, anacetrapib, and, likely, evacetrapib. As such, the quest for the holy grail in coronary disease has many worthy knights on the trail," he wrote.

If evacetrapib proves in future long-term studies to be safe and effective, it could provide a therapeutic option for a subgroup of patients that are difficult to treat.

"The best case scenario for this drug is the patient who has a lipid disorder and is being managed with a statin, but still has a low HDL that won't come up despite interventions to raise HDL, like exercise, and doctors are still concerned about cardiovascular risk," said Patterson.

"As good as stains have been, there are still a lot of people that have clinical events, like a heart attack," said Nicholls. "Statins aren't going to be enough for many people."

In an accompanying editorial, Dr. Christopher Cannon of Brigham and Women's Hospital in Boston, said evacetrapib is one of several promising HDL-raising options currently being tested.

"Further interventions await data from the large randomized trials of current therapies (e.g., niacin) and emerging therapies like the CETP inhibitors, including dalcetrapib, anacetrapib, and, likely, evacetrapib. As such, the quest for the holy grail in coronary disease has many worthy knights on the trail," he wrote.

If evacetrapib proves in future long-term studies to be safe and effective, it could provide a therapeutic option for a subgroup of patients that are difficult to treat.

"The best case scenario for this drug is the patient who has a lipid disorder and is being managed with a statin, but still has a low HDL that won't come up despite interventions to raise HDL, like exercise, and doctors are still concerned about cardiovascular risk," said Patterson.

"As good as stains have been, there are still a lot of people that have clinical events, like a heart attack," said Nicholls. "Statins aren't going to be enough for many people."