Restenosis is the term used to describe arteries that re-narrow following stenting, often because of accumulation of new tissue similar to scar tissue. When researchers gave the investigational drug everolimus to animals that underwent stenting, they discovered the drug reduced the growth of scar tissue in the stent from 46 percent to 40 percent depending upon the dose of drug given, says Renu Virmani, M.D., senior author of the study.
Recent advances using new and better stents combined with radiation treatments dramatically reduced the complication rate from stenting. Another experimental approach using drug-eluting stents is associated with even lower restenosis rates, but neither radiation nor the special coated stents completely eliminated the problem.
"Everolimus is very similar to another drug, sirolimus, that has shown promise in treatment of restenosis. The advantage of using an oral drug rather than a coated stent is that it gives us more control. With a stent, we don't know when the drug finishes working. With an oral drug we can give it for a short time, and then monitor its effect," says Virmani, chair, department of cardiovascular pathology, Armed Forces Institute of Pathology, Washington, D.C.
Six New Zealand white rabbits received 1.5mg/kg per day of everolimus starting three days before stenting, which was reduced to 1 mg/kg per day from days 14 to 28 after stenting. Six others received a lower dose – 1.5 mg/kg per day for one day before stenting followed by 0.75 mg/k for 28 days. Matching placebo groups were established for each treatment group.
Virmani says the rabbits receiving the high dose everolimus experienced loss of appetite and weight loss that was resolved by lowering the dose. When Virmani's team measured the thickness of the vessel wall they found that the high dose treatment was associated with a 46 percent reduction in intimal thickness compared to placebo while the lower dose reduced thickening by 40 percent compared to placebo. She says the drug is currently being studied as a treatment to prevent organ rejection in patients who undergo kidney transplantation. Virmani says she would like to study everolimus in patients who undergo stenting but she said there are no current plans for a clinical study of the drug in heart patients.
In an editorial that accompanies the study, David P. Faxon, M.D., cardiology section chief at the University of Chicago, writes that finding an effective pill to prevent restenosis would "allow more flexibility in a choice of the type of stent to be used. It could also be used as an adjunct in very high risk cases or recurrent restenosis. It's also possible that an effective oral agent might reduce the need for stenting altogether since stents have not been shown to be of value in certain circumstances such as small vessels smaller than 2.5mm in diameter."
But Faxon, who is a former president of the American Heart Association, cautioned that successful animal studies don't always translate into successful treatments in humans. He also notes that the first attempts at preventing restenosis concentrated on oral medications and those attempts were unsuccessful.
Novartis Pharmaceuticals Corp., East Hanover, New Jersey funded the study.
Virmani's coauthors are Andrew Farb, M.D.; Michael John, B.A.; Eduardo Acampado, D.V.M.; Frank D. Kolodgie, Ph.D.; and Margaret Forney Prescott, Ph.D.
ADDITIONAL CONTACT INFORMATION:
For journal copies only,
please call: 214-706-1396
For other information, call Carole Bullock: 214-706-1279 or Maggie Francis: 214-706-1397