Heart News
March 25, 2007
Cleveland Clinic researchers 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-á) agonist. The new drug, LY518674 (LY5) is similar to an existing agent, fenofibrate, but is approximately 10,000 times more potent.
Steven Nissen, MD, Chairman of Cardiovascular Medicine at Cleveland Clinic and lead investigator of this study, will present "Efficacy and Safety of a Potent New PPAR-Alpha Agonist as Monotherapy or in Combination With Statins in Subjects With Dyslipidemia," on Sunday, March 25, at 1:30 p.m. at the American College of Cardiology’s (ACC) 56th Annual Scientific Session in New Orleans. Dr. Nissen is also President of the ACC. This study will be simultaneously published in the Journal of the American Medical Association (JAMA).
Dr. Nissen reports that despite the potency of this new drug, it showed no advantages compared with 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," Dr. Nissen reports. "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 (TRIGS) and a decrease in "good" high-density lipoprotein (HDL) levels in the blood. This lipid disorder is associated with an increased risk of developing cardiovascular disease.
Although statins represent the primary treatment of patients with abnormal cholesterol levels (by lowering LDL or "bad cholesterol"), these drugs have limited effects on HDL or TRIGS. Therefore, researchers have explored the use of treatments targeting PPAR-alpha family to reduce TRIGS and raise HDL. This approach has shown benefits in reducing adverse outcomes in some, but not all, studies of cardiovascular disease.
In one of the two studies, 309 atherogenic dyslipidemia patients, were randomized into six treatment groups and efficacy was measured by change in lipid levels during 12-weeks treatment. Both fenofibrate and LY5 markedly decreased triglycerides 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 of the two studies, LY5 was studied in patients with elevated levels of LDL cholesterol with or without treatment using a statin (atorvastatin). 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.
Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual "America’s Best Hospitals" survey. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2005, there were 2.9 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were nearly 54,000 hospital admissions to Cleveland Clinic in 2005.
The American College of Cardiology represents the majority of board certified cardiovascular physicians in the United States. Its mission is to advocate for quality cardiovascular care through education, research, promotion, development and application of standards and guidelines- and to influence health care policy. ACC.07 and the ACC inaugural i2 Summit, the first-ever meeting for interventional cardiologists, will bring together more than 30,000 cardiologists and cardiovascular specialists to share the newest discoveries in the treatment and prevention, while helping the ACC achieve its mission to address and improve issues in cardiovascular medicine.
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