April 7, 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
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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.
PENN Medicine is a $2.5
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patient care. PENN Medicine consists of the University
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Penn’s School of Medicine is ranked #2 in the
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