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April 07, 2004
Increasing the Body’s Good Cholesterol May be
a Pill Away
Study Pinpoints Protein Inhibitor that Raises HDL Levels
(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.
###
Editor’s Notes
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.
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to the related missions of medical education, biomedical research, and high-quality
patient care. PENN Medicine consists of the University of Pennsylvania School
of Medicine (founded in 1765 as the nation’s first medical school) and
the University of Pennsylvania Health System (created in 1993 as the nation’s
first integrated academic health system).
Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH
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practice plan, a primary-care provider network, three multispecialty satellite
facilities, and home health care and hospice.
Release available online at http://www.uphs.upenn.edu/news/News_Releases/apr04/increasingcholesterol.html