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ATTRACT - clot-busting drugs do not benefit most patients with DVT

The researchers noted a worrisome increase in the number of people who developed major bleeding after undergoing the procedure

The results of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) study have revealed that clot busting drugs and medical devices do not improve outcomes for patients experiencing deep vein thrombosis (DVT), nor do they prevent the development of post-thrombotic syndrome (PTS) when compared with conventional blood thinning medications.

The outcomes from the ATTRACT study, ‘Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis’, published in the New England Journal of Medicine, showed that clearing the clot with drugs and specialized devices did not reduce the likelihood that patients would develop post-thrombotic syndrome, a complication that can leave patients with chronic limb pain and swelling, and can lead to difficulty walking or carrying out their daily activities. Use of the potent drugs did, however, raise the chance that a patient would experience a dangerous bleed.

"We found no particular advantage to employing clot busters and do not believe they should be applied to the majority of patients who present with acute DVT. Moreover, clot busters are associated with a higher risk for dangerous bleeding," said Dr Susan Kahn of the Centre for Clinical Epidemiology at the Lady Davis Institute of the Jewish General Hospital. She is an internationally recognized expert in the treatment of DVT and Director of the Hospital's Centre of Excellence in Thrombosis and Anticoagulation Care (CETAC). Kahn, who is also a professor of medicine at McGill University in the department of Epidemiology, Biostatistics and Occupational Health, chaired the Clinical Outcomes Committee for the ATTRACT Trial and is a member of the trial's steering committee.

ATTRACT is a randomised controlled trial primarily funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) – 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. It was initiated in 2008, following a call to action on DVT and, specifically, for research into the benefits and risks of removing clots issued by the then-Acting Surgeon General of the United States, Dr Steven K Galson.

The study involved 692 patients at 56 clinical sites, randomly assigned to receive blood thinners alone or blood thinners and the procedure. Each patient was followed for two years. Complications developed in 157 of 336 (47%) of people who underwent the procedure and 171 of 355 (48%) of people who did not, a difference that was not statistically significant. The procedure did reduce the severity of PTS, 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 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%) among those who received clot busting drugs – the potential for catastrophic bleeding is why these drugs are usually reserved for life-threatening emergencies such as heart attacks and strokes. Furthermore, the procedure is expensive and often requires a hospital stay.

"There is a suggestion that this intervention is effective in reducing more severe cases of PTS, but this calls for further study," said Kahn. "The practice at the JGH has been to offer such treatments only in rare cases of very extensive DVT of the leg and, on occasion, of the arm, where the swelling is so significant that we fear the onset of limb gangrene. We are confident that we have been using these therapies properly and will continue with our existing protocols. This study's results also highlight that new approaches to preventing PTS are needed."

"What we know now is that we can spare most patients the need to undergo a risky and costly treatment," said principal investigator, Dr Suresh Vedantham, a professor of radiology and of surgery at Washington University School of Medicine in St Louis. "We are dealing with a very sharp double-edged sword here. 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."

Suresh Vedantham

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 post-thrombotic syndrome," Vedantham said. "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 some carefully selected patients, who are experiencing particularly severe limitations of leg function from deep vein thrombosis and who are not responding to blood-thinners, Vedantham added.

"The clinical research in deep vein thrombosis and post-thrombotic syndrome is very important to the clinical community and of interest to the National Heart, Lung, and Blood Institute," said Dr Andrei Kindzelski, 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."