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.
About PENN Medicine
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.
Journal
New England Journal of Medicine