Pill Prevents Rabbit Stents from Re-Blocking
Scientists hope trial drug does the same in humans with cardiovascular disease
WEDNESDAY, Oct. 2, 2002 (HealthDayNews) -- While researchers studying rabbits' response to an experimental drug aren't exactly hopping with excitement, they are cautiously optimistic that a pill containing the medication will let stents restore blood flow in clogged arteries without complications.
A stent is a wire mesh tube that cardiac specialists use to prop open a clogged artery after angioplasty has removed arterial blockage. It works like a permanent scaffold and keeps the artery walls spread apart. In as many as a third of patients who undergo the procedure, however, the artery narrows again because of scar tissue accumulating at the stent site, a re-narrowing known as restenosis. The condition typically requires at least one more angioplasty, and sometimes even more aggressive medical interventions.
Vice President Dick Cheney's experience with restenosis elevated the condition to headline news briefly last year.
A new study from researchers at the Armed Forces Institute of Pathology suggests that orally administered everolimus, one of a class of drugs known as proliferation inhibitors, may prevent new blockage at stent sites.
"Depending on the dose of the medication administered to the animals in our study, the growth of scar tissue was reduced between 40 to 46 percent," says research leader Dr. Renu Virmani, head of cardiovascular pathology at the institute. "Although there have been other promising advances in treating restenosis that use radiation or stents that slowly release a medication, I believe an orally administered drug like everolimus provides a better, more cost-effective long-term solution."
The study appears in the current issue of Circulation.
Virmani and her colleagues gave six white rabbits everolimus orally for three days before and 28 days after stent surgery. Six other rabbits were given a lower dose of everolimus for one day before and 28 days after surgery, and six were used as controls for each experimental group.
The rabbits given the higher dose of everolimus experienced loss of appetite and weight loss, but they also had a reduction of 46 percent in the thickness of their artery walls compared to rabbits that received no medication, Virmani says. Rabbits on the lower dose of everolimus had fewer side effects and a reduction of 40 percent in artery thickness compared to the control group.
"Although I would like to study everolimus in individuals who undergo stent procedures, there are presently no plans for clinical trials with human patients," says Virmani. "Most of the interest now is in pursuing solutions that I believe will be more expensive in the long run."
Novartis Pharmaceuticals Corp., which funded Virmani's research, has completed human clinical trials evaluating the safety and efficacy of an orally administered drug containing everolimus for the prevention of organ rejection in renal and heart transplant recipients. In March 2002, Novartis granted Guidant Corp. the rights to use everolimus in manufacturing stents for the treatment of coronary and peripheral vascular diseases, including stenosis. Early next year, Guidant expects to start clinical trials of the device -- which will be among the class generically referred to as drug-eluting coronary stents.
Dr. David P. Faxon, cardiology section chief at the University of Chicago and former president of the American Heart Association, acknowledges in an accompanying editorial that a pill to help prevent restenosis would have a wide range of uses in coronary artery disease treatment. However, he warns, there's no way to know yet if everolimus is the pill to do it or whether any oral medication will work.
"Successful animal studies are one thing," Faxon says, "but they don't always translate into successful treatments for humans. The very first attempts at treating restenosis focused on oral medications, too. But despite some promising first results, these medications eventually proved unsuccessful."
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