By Tamara Bhandari
About one-half of people with blood clots in the deep veins of their legs—a condition known as deep vein thrombosis (DVT)—develop a complication that involves chronic limb pain and swelling, making it difficult for some to walk and perform daily activities. A large-scale, multicenter clinical trial has shown that a risky, costly procedure to remove such clots fails to reduce the likelihood that patients will develop the debilitating complication. According to the trial's results, not all patients with DVT need to receive powerful but risky clot-busting drugs. The findings were published in The New England Journal of Medicine.
The study showed that clearing the clot with drugs and specialized devices did not reduce the likelihood that patients would develop postthrombotic syndrome, a complication that can leave patients with chronic limb pain and swelling and can lead to difficulty walking or carrying out daily activities. Use of the potent drugs did, however, raise the chance that a patient would experience a dangerous bleed.
"What we know now is that we can spare most patients the need to undergo a risky and costly treatment," says principal investigator Suresh Vedantham, MD, a professor of radiology and surgery at Washington University School of Medicine in St. Louis.
Between 300,000 and 600,000 people a year in the United States are diagnosed with a first episode of DVT, and, despite standard treatment with blood thinners, roughly one-half will develop postthrombotic syndrome. There is no treatment to prevent the potentially debilitating complication. However, small studies have suggested that a procedure that delivers clot-busting drugs directly to the clot may reduce the chance the syndrome will develop. The procedure is currently used as a second-line treatment to alleviate pain and swelling in people who do not improve on blood thinners.
The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) study—a randomized controlled trial primarily funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health—was designed to determine whether performing the procedure as part of initial treatment for patients when they are first diagnosed with DVT would reduce the number of people who later develop the syndrome. In 2008, then-Acting Surgeon General Steven K. Galson, MD, issued a national call to action on DVT and specifically called for research into the benefits and risks of removing clots.
"The clinical research in deep vein thrombosis and postthrombotic syndrome is very important to the clinical community and of interest to the National Heart, Lung, and Blood Institute," says Andrei Kindzelski, MD, PhD, the NHLBI program officer for the ATTRACT trial. "This landmark study, conducted at 56 clinical sites, demonstrated in an unbiased manner no benefits of catheter-directed thrombolysis as a first-line deep vein thrombosis treatment, enabling patients to avoid an unnecessary medical procedure. At the same time, ATTRACT identified a potential future research need in more targeted use of catheter-directed thrombolysis in specific patient groups."
The study involved 692 patients, randomly assigned to receive blood thinners alone or blood thinners and the procedure. Each patient was followed for two years.
During the procedure, doctors insert a thin, flexible plastic tube through a tiny incision in the leg and navigate it through the veins using X-ray and ultrasound guidance, until it rests within the clot. They instill a drug known as tissue plasminogen activator through the tube, give it time to digest the clot, and then suck out or grind up any remaining fragments using specialized catheter-mounted devices. The procedure is expensive, costing thousands of dollars, and often requires a hospital stay.
The clinical trial showed that routine use of the procedure did not reduce the chance of developing postthrombotic syndrome. The complication developed in 157 of 336 (47%) people who underwent the procedure and 171 of 355 (48%) people who did not, a difference that is not statistically significant.
The procedure did reduce the severity of postthrombotic syndrome, easing patients' long-term symptoms. About 24% of people on blood thinners alone experienced moderate to severe pain and swelling, but only 18% of people who were treated with blood thinners and clot busters did so. The procedure also alleviated pain and swelling in the early stages of the disease, when patients are often very uncomfortable.
However, the researchers noted a worrisome increase in the number of people who developed major bleeding after undergoing the procedure. While the numbers were small—one patient (0.3%) on standard treatment experienced a bleed, compared with six (1.7%) of those who received clot-busting drugs—and none of the bleeds was fatal, any increase in bleeding is a red flag. The potential for catastrophic bleeding is why powerful clot-busting drugs usually are reserved for life-threatening emergencies such as heart attacks and strokes.
"We are dealing with a very sharp double-edged sword here," says Vedantham, who is also an interventional radiologist at the university's Mallinckrodt Institute of Radiology. "None of us was surprised to find that this treatment is riskier than blood-thinning drugs alone. To justify that extra risk, we would have had to show a dramatic improvement in long-term outcomes, and the study didn't show that. We saw some improvement in disease severity but not enough to justify the risks for most patients."
While the study showed that most patients should not undergo the procedure, the data hint that the benefits may outweigh the risks in some patients, such as those with exceptionally large clots.
"This is the first large, rigorous study to examine the ability of imaging-guided treatment to address postthrombotic syndrome," Vedantham says. "This study will advance patient care by helping many people avoid an unnecessary procedure. The findings are also interesting because there is the suggestion that at least some patients may have benefited. Sorting that out is going to be very important. The ATTRACT trial will provide crucial guidance in designing further targeted studies to determine who is most likely to benefit from this procedure as a first-line treatment."
For now, the procedure should be reserved for use as a second-line treatment for carefully selected patients who are experiencing particularly severe limitations of leg function from DVT and who are not responding to blood thinners, Vedantham adds.
The ATTRACT study was led by researchers at Washington University; McMaster University in Ontario, Canada; Massachusetts General Hospital in Boston; and St. Luke's Mid-America Heart Institute in Kansas City, Missouri.Source: Washington University School of Medicine in St. Louis