Once-promising cholesterol drug fails to improve patients' heart health

Despite its success in lowering LDL -- known as "bad" cholesterol -- while increasing levels of "good" cholesterol HDL, the drug evacetrapib is not effective in helping protect patients from major cardiovascular events like heart attack and stroke, a large clinical trial finds.

The research, presented at the American College of Cardiology's 65th Annual Scientific Session on Sunday, explains why the drug's maker, Eli Lilly, halted the study in October.

"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," lead study author Dr. Stephen Nicholls, a professor at Australia's University of Adelaide and cardiologist at Royal Adelaide Hospital, said in a statement. "We were disappointed and surprised by the results."

The study involved more than 12,000 patients from approximately 540 global health centers at high risk for serious cardiovascular health problems. The participants were randomly selected to receive either 130 milligrams of evacetrapib or a placebo pill daily for at least 18 months. The patients also received standard medical therapy -- the majority of which included statins or other cholesterol-lowering drugs -- throughout the trial.

The research showed that, on average, patients taking evacetrapib lowered their "bad" cholesterol by 37 percent and increased their "good" cholesterol by 130 percent compared to the other patients taking the placebo. However, the drug's favorable effects on cholesterol did not translate into a reduced risk of heart attack, stroke, coronary artery bypass surgery, hospitalization for chest pain, or amount of time until cardiovascular death.

This marks the third failure in a class of drugs known as cholesteryl ester transfer protein (CETP) inhibitors, which are made to disrupt the natural process by which HDL cholesterol is converted into LDL cholesterol in the body. The first drug was abandoned after it was found to increase the risk of heart trouble and death. The second was deemed ineffective.

"There has been, and continues to be, a lot of confusion about what's going on with this class of drugs, since we don't yet have one that can be brought to the clinic to prevent heart attack and stroke in our patients," Nicholls said. "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."

Though researchers don't know the answer to this question, some have hypotheses.

"As we learn more about this class of medications, perhaps it is not enough to raise HDL and lower LDL and see beneficial effects," Dr. Jeffrey Kuvin, a cardiologist at Tuft's Medical Center and the co-chair of the 2016 ACC meeting, told CBS News.

Another possible explanation, Nicholls said, is that existing treatments like statins are already so effective at improving heart health that it has become more difficult to further improve outcomes in high-risk patients. Or it may be that evacetrapib's active ingredient or the biological pathway it is designed to affect simply has no effect on cardiovascular risk.

Whatever the reason, experts say CETP's are looking less and less like a viable option to treat and prevent heart problems in high risk patients.

"As we gain further evidence with this class of medications," Kuvin said, "there is further skepticism as to whether or not these drugs are actually going to be effective in the treatment of cardiovascular disease."