Clot-Busters As Effective As Surgery To Clear Blockages In Legs

April 15, 1998

First they were shown to restore blood flow during a heart attack. Then doctors used them to save the brain during a stroke. Now, physicians have shown that clot-busting drugs (thrombolytics) can save the legs, too, as effectively as invasive surgery. The study, the largest to compare a thrombolytic agent to surgery in patients with arterial blockages in the legs, is published in the April 16 issue of the New England Journal of Medicine.

In the study of 544 patients at 113 sites across North America and Europe, physicians compared patients who had immediate surgery to patients who were first given a clot- dissolving agent. The compound doctors used was an experimental form of recombinant urokinase made by Abbott Laboratories, which funded the study.

"This study shows conclusively that this drug minimizes the need for surgery," says first author Kenneth Ouriel, a University of Rochester vascular surgeon and a principal investigator of the study. "Lots of people, including many surgeons, still think that if you have a blocked artery in the leg, you need an operation. That's not necessarily true any longer."

Frank Veith of the Montefiore Medical Center/Albert Einstein College of Medicine in New York City, president of the Society of Vascular Surgery, was the co-principal investigator. Arthur Sasahara, formerly with Abbott Laboratories and now at Harvard, also helped to coordinate the study.

The team studied what doctors call acute ischemia of the legs: Just as in a heart attack or most strokes, it's caused when patients develop sudden arterial blockage that cuts off blood flow. The condition is very painful, and many patients end up having the leg amputated. Such patients are usually elderly and have another disease, such as heart disease, cancer, or diabetes; the condition occurs in more than 40,000 people in the U.S. each year.

Physicians found no statistically significant difference in the rate of death or amputation, whether patients received conventional surgical treatments or the drug. Moreover, the length of hospital stay was similar in the two groups. The team did notice an increased risk of bleeding in the urokinase group.

The clot-buster the team studied is an experimental compound known as recombinant urokinase. Standard urokinase, marketed as Abbokinase by Abbott, is approved to clear blood clots in the heart and lungs and is often used by physicians to treat blood clots in the legs. The overall cost of surgery and the cost of the medication are about the same, says Ouriel, noting that a typical supply of the drug for one patient costs the hospital about $3,500.

"For many surgeons today, the standard of care for these patients is to take them urgently to the operating room," says Ouriel. "Our results show that patients receiving urokinase can experience success rates equivalent to that of surgery, but the frequency and extent of open surgical procedures is reduced."

More than 30 percent of patients avoided open surgical procedures by using the drug, the physicians found. Of those taking the drug who then went on to have surgery, the operation was often less invasive than would have been required without the drug -- for instance, patching a narrow segment of an artery rather than placing a completely new bypass graft.

Even with all of these options -- drugs, surgery, or a combination -- about one-quarter of patients died or lost their leg within six months.

Ouriel says that in major medical centers, thrombolysis is often the first treatment patients receive, but word is just beginning to spread to all vascular surgeons.

"Instead of taking these patients to the operating room immediately, we can infuse a thrombolytic agent over a day or so," says Ouriel. "If we do need to operate, it's frequently a much smaller operation, such as patching one small area. Thrombolysis lets surgeons be selective in whom they operate on, and converts an emergency procedure to an elective one."

Not all physicians are as enthusiastic. In an accompanying editorial in the journal, John Porter of the Oregon Health Sciences University School of Medicine concludes from the same data that drug therapy does not improve clinical outcome. Citing the increased risk of bleeding, he concludes, "For the time being, I do not regard thrombolytic therapy as first-line treatment for acute arterial thromboembolism of the legs."

Like Ouriel, co-author Veith disagrees, saying the study does support the idea that drugs should be a part of the treatment regimen. "These drugs have a useful place in the treatment of acute arterial blockages in the legs. Urokinase spares fairly aggressive and invasive treatment in a number of cases."
-end-


University of Rochester

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