(Philadelphia, PA) – An important clinical advance in the prevention of heart disease has been identified by researchers at the University of Pennsylvania School of Medicine, in collaboration with researchers at Tufts University and Pfizer. The study led by Daniel Rader, MD, Associate Professor of Medicine and Director of Penn's Preventive Cardiovascular Medicine & Lipid Center, involved a novel pharmacologic approach – inhibition of the cholesteryl ester transfer protein (CETP) – and showed that this approach is highly effective in raising high-density lipoprotein (HDL) levels in patients with low levels. The study will be published in the April 8th issue of The New England Journal of Medicine.
The drug torcetrapib, made by Pfizer, significantly increased levels of HDL in patients with low levels of this "good" cholesterol, whether or not they were also being treated with the cholesterol-lowering drug atorvastatin (Lipitor). The combination therapy used in the trial proved so effective that, among those patients who received the highest dosages of both drugs, HDL cholesterol levels were increased by more than 100%. "These results are striking because it is generally very difficult to raise HDL levels in people with already low-levels of good cholesterol," said Rader.
According to Rader, torcetrapib works by inhibiting the ability of the cholesteryl ester transfer protein to transfer cholesterol from HDL (the "good" cholesterol) into LDL (the "bad" cholesterol). And, although the drug's CETP-inhibitor properties proved effective when administered by itself, its effectiveness was maintained when given in combination with a statin -- which is the most common class of drugs used to lower LDL cholesterol levels.
The implications of this study – which took place at Penn and Tufts/New England Medical Center, Boston -- could have far-reaching effects when it comes to heart disease. A low level of HDL cholesterol is the most common lipid abnormality observed in patients with known coronary heart disease. Torcetrapib is still in clinical development but is designed as chronic long-term therapy to raise HDL levels and reduce heart disease risk, just as statins are used to lower LDL levels. Further studies are being done to determine whether it successfully reduces the risk of heart disease.
Researchers also contributing to this study include Margaret E. Brousseau, PhD, Ernst J. Schafer, MD (Lipid Research Laboratory, Division of Endocrinology, Metabolism, Diabetes, and Molecular Medicine, New England Medical Center and Tufts University, Boston), Megan L. Wolfe, BS, LeAnn T. Bloedon, MS, RD (the Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia), Andres G. Digenio, MD,PhD, Ronald W. Clark, MS, and James P. Mancuso, PhD from Pfizer in Groton, Connecticut.
This investigator-initiated study was funded in part by Pfizer, which is developing torcetrapib. The General Clinical Research Center at the Hospital of the University of Pennsylvania provided additional funding.
Dr. Rader has received lecture and consultation fees from Pfizer, as well as grant support. Members of the public seeking more information on this study may call 888.81 HEART or (215) 573-7662 and ask for Ms. Hughes.
The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.
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