Cleveland Clinic Scientist Presents Data on Cholesterol Drugs

Cleveland Clinic researchers announced they have recently completed a pair of studies to determine the safety and efficacy of a new, potent type of cholesterol treatment known as a peroxisome proliferator-activated receptor alpha (PPAR-alpha) agonist. The new drug, Eli Lilly's LY518674 (LY5), is similar to an existing agent, Abbott's TriCor, but is approximately 10,000 times more potent, according to the researchers.

The study results were presented at the American College of Cardiology's 56th Annual Scientific Session in New Orleans and will be published in The Journal of the American Medical Association.

Steven Nissen, chairman of Cardiovascular Medicine at the Cleveland Clinic and lead investigator of this study, reported that despite the potency of this new drug, it showed no advantages compared with TriCor (fenofibrate). Moreover, both LY5 and fenofibrate raised safety concerns, according to the studies.

"Our study found that both LY518674 and fenofibrate decreased triglycerides (fat) and increased HDL-C (good cholesterol) for patients with dyslipidemia. However, LY5 also increased levels of LDL or bad cholesterol, and both drugs showed evidence of worsening kidney function," Nissen said. "These results suggest the new PPAR agonists will not likely offer important advantages over existing drugs."

LY5 was intended to be effective in treating atherogenic dyslipidemia, a cholesterol disorder characterized by the elevation of triglycerides and a decrease in HDL levels in the blood.

In the first study, 309 atherogenic dyslipidemia patients were randomized into six treatment groups and efficacy was measured by change in lipid levels during 12 weeks of treatment. Both fenofibrate and LY5 markedly decreased triglyceride levels and increased levels of HDL. LY5 produced a modest increase with the lowest dose, maximum increases with an intermediate dose and less increase with higher dosages.

In the second study, LY5 was studied in patients with elevated levels of LDL with or without treatment using a statin. In this population, LY5 lowered triglycerides, raised HDL, and slightly lowered LDL. These effects were similar to results obtained in previous studies using fenofibrate.

In the dyslipidemia study, both fenofibrate and LY5 increased levels of creatinine, suggesting the potential for an adverse effect on kidney function, according to the researchers.