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."

University of Rochester

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to