Healthcare Industry News: torcetrapib
News Release - November 5, 2007
Cleveland Clinic Study Suggests Failure of HDL-Raising Drug Torcetrapib is Likely Compound Specific
ORLANDO, Fla., Nov. 5 (HSMN NewsFeed) -- Cleveland Clinic researchers today reported that the drug torcetrapib produced regression of coronary atherosclerosis in patients who achieved the greatest increases in high- density lipoprotein (HDL) or "good" cholesterol.These findings suggest that the HDL particles are fully functional during treatment with torcetrapib and the lack of efficacy likely reflects a compound-specific toxicity, which is also responsible for the increase in blood pressure.
Steven Nicholls, M.D., Ph.D., Director of the Cleveland Clinic Intravascular Ultrasound Lab and the study's Lead Investigator, presented "Changes in Levels of High-Density Lipoprotein Cholesterol Predict the Impact of torcetrapib on Progression of Coronary Atherosclerosis: Insights from ILLUSTRATE" at the American Heart Association's (AHA) 27th Annual Scientific Session currently underway in Orlando, Fla.
The research provides strong evidence that raising HDL predicts the drug's benefit and indicates that additional clinical study of other experimental drugs in this class is necessary.
"In this study, we also examined the effect of torcetrapib on blood pressure and electrolyte changes in order to investigate the potential mechanisms of toxicity," Dr. Nicholls said. "What we found was that the increased blood pressure and changes in electrolytes signal the potential activation of the renin-angiotensin-aldosterone system (RAAS) by torcetrapib. The greater RAAS activation may weaken the benefit of raising HDL."
Researchers report that the lack of efficacy may reflect an off-target toxicity directed at the RAAS. Therefore, determining that other inhibitors of cholesterylester transfer protein (CETP), or medications in the same class as torcetrapib without potential RAAS toxicity may, be efficacious.
The development of drugs to raise HDL has been a key research priority because, despite lowering LDL (low-density lipoprotein, or "bad" cholesterol) with statin drugs, many patients continue to experience heart attacks, stroke or sudden cardiac death.
A total of 1,188 coronary artery disease patients were enrolled in the ILLUSTRATE trial, which initially determined that torcetrapib markedly increased good cholesterol levels, but also substantially raised blood pressure and failed to significantly slow the buildup of plaque. The initial trial manuscript was published in the New England Journal of Medicine in March.
ILLUSTRATE used the intravascular ultrasound (IVUS) technology to determine the findings. IVUS is a technique in which a tiny ultrasound probe is inserted into the coronary arteries, providing a precise and reproducible method for determining the change in plaque, or atheroma, burden during treatment.
ILLUSTRATE principal investigator Dr. Steven Nissen MD, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic, commenting on Dr. Nicholls findings, said "These observations offer new hope that raising HDL by inhibiting CETP may ultimately succeed in slowing the progression of coronary heart disease and reducing cardiovascular events. New studies with agents other than torcetrapib seem warranted."
Cleveland Clinic Heart & Vascular Institute is the recognized world leader in diagnosis and treatment of cardiovascular disease. Cleveland Clinic has been ranked No. 1 in the nation for cardiac care by U.S. News & World Report every year since 1995. Cleveland Clinic has been ranked among America's Ten Best Hospitals every year since 1990 by U.S. News & World Report.
Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2006, there were 3.1 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were more than 53,000 hospital admissions to Cleveland Clinic in 2006. Cleveland Clinic's Web site address is www.clevelandclinic.org.
Source: Cleveland Clinic
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