Cleveland Clinic Researchers Find No Benefit to HDL-Raising Injection In Regression Of Coronary Heart Disease

NEW ORLEANS: Cleveland Clinic researchers have found that infusions of MDCO-216 – a drug meant to enhance high-density lipoprotein, or HDL, the so-called “good cholesterol – did not have a favorable effect on coronary disease progression.

For decades it’s been suggested that HDL protects against cardiovascular disease. However, researchers have yet to show that HDL-raising agents are effective in reducing cardiovascular events. ApoA-1 Milano was originally discovered in the 1970’s in a small village in Northern Italy, where the residents had the HDL compound apolipoprotein in their blood and had low risk for cardiovascular disease.

The double-blinded, placebo-controlled, randomized MILANO-PILOT study was designed to determine whether MDCO-216, which contains ApoA-1 Milano, would have any benefit in reducing plaque build-up within the arteries of patients who had recent acute coronary disease.

However, while patients receiving placebo saw their HDL levels improve slightly, those treated with MDCO-216 saw their HDL levels decline. The study’s findings support the decision to stop further development of MDCO-216.

“The failure to show benefits with the MDCO-216 further challenges the hope that medical therapy will raise HDL in patients,” said Dr. Stephen J. Nicholls, MBBS, Ph.D., FRAP, South Australian Health and Medical Research Institute. “With new agents continuing to be researched we will hopefully find out how the HDL story plays out.”

Dr. Nicholls presented the MILANO-PILOT results today at the American Heart Association Scientific Sessions in New Orleans. Steven Nissen, M.D., chairman of the Robert and Susan Tomsich Department of Cardiovascular Medicine at Cleveland Clinic, co-directed the study with Dr. Nicholls.

The trial enrolled 120 patients globally, who were randomized by site and by previous statin use. The placebo arm had 61 patients with a mean HDL baseline of 41.0 mg/dL, while the MDCO-216 arm had 52 patients with a mean HDL baseline of 44.0 mg/dL. (Seven patients dropped out.). Patients were given five infusions of MDCO-216 at a dose of 20 mg/kg over the course of six weeks.

The primary endpoint of the study measured the volume of plaque in the arteries. Those taking a placebo showed a 0.8 percent reduction in plaque, compared to 0.5 in the MDCO-216 group. More patients in the placebo group experienced plaque regression (67.2 percent) than those who received MDCO-216 (55.8 percent).

The study was funded by The Medicines Company. Dr. Nissen has served as a consultant for many pharmaceutical companies and has overseen clinical trials for Amgen, AstraZeneca, Cerenis, Eli Lilly, Novartis, Novo Nordisk, The Medicines Company, Orexigen, Takeda and Pfizer. However, he does not accept honoraria, consulting fees or other compensation from commercial entities.