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.

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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.

PENN Medicine is a $2.5 billion enterprise dedicated 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 research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System consists of four hospitals (including its flagship Hospital of the University of Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report), a faculty practice plan, a primary-care provider network, three multispecialty satellite facilities, and home health care and hospice.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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