Surgeon General Steven K. Galson, MD, MPH, with Suresh Vedantham, MD issued a Call to Action to reduce the number of cases of DVT and pulmonary embolism in the U.S. courtesy SIR

Suresh Vedantham, MD, is an associate professor of radiology and surgery at the Washington University School of Medicine and the lead investigator in the ATTRACT trial, the first multicenter, randomized clinical trial to investigate the long-term efficacy of a new treatment for DVT. In an interview with ADVANCE, Dr. Vedantham discussed the evolution of DVT management, the technologist's role in an innovative procedure and his hope for a "major paradigm shift" in the treatment and prevention of common and potentially deadly conditions.

ADVANCE: Why is it important to find a way to treat DVT and prevent PTS?

DVT occurs as a first episode in about 250,000 Americans each year and causes two main complications. The first one that's well known is pulmonary embolism, which is a clot breaking off and moving to the lungs. That can be fatal and is estimated to kill over 100,000 Americans each year. The second problem, which is less talked about, is called post-thrombotic syndrome, whereby the clot remains in the vein and in the long run does permanent damage to the vein, with the result that patients develop long-term, significant, life-altering symptoms such as pain in the leg when they walk, swelling of the leg, heaviness and fatigue. That can progress to even worse problems such as open sores or ulcers on the leg.

Treating DVT properly is important, and so is paying particular attention not just to the short-term problem of pulmonary embolism but to the long-term problem of PTS. I think the [medical] community is now learning that this is important to do.

ADVANCE: Can you tell me about the significance of Surgeon General Galson's Sept. 15, 2008 Call to Action addressing the issue of pulmonary embolism prevention and the need for more research into the treatment of DVT?

I am the vice chairman of the Venous Disease Coalition, which is a 34-organization coalition of healthcare professional organizations dedicated to increasing public awareness and education on venous disease. The Surgeon General chose our annual meeting to issue his Call to Action.

The Call to Action itself has been under development for over two to three years now. In 2006, the Surgeon General held an invitation-only workshop in Bethesda, Maryland to look at DVT as a serious public health threat. He concluded that, indeed, it is, and committed to issuing the Call to Action, which finally came out on Sept. 15, 2008.

I think it really showed a significant vision on the part of the Surgeon General and the NIH to come out with this Call to Action, because it addressed not just the issue of pulmonary embolism prevention but also, if you read the content, the need for further research into the treatment of DVT, in particular in clot removal treatments. What that means is that there is finally high-level awareness of the problems of PTS and PE and how they impact patients' lives, as well as the fact that both may be preventable. That's worth telling the American public.

ADVANCE: What methods are currently used to treat DVT? Why are they insufficient?

It's important to emphasize that anticoagulant drugs are very important to give, because they do prevent the clot from growing and breaking off and going to the lungs. Certainly, anticoagulant therapy is essential in the setting of DVT to prevent PE, and also to prevent new episodes of DVT. You may see some effect on preventing the long-term complications as well. However, because anticoagulants, which are basically blood thinning drugs, don't actually dissolve the clot, the clot remains in the leg and does cause PTS. Overall, if you look at patients with what's known as proximal DVT of the leg, which means from the knee up, you find that somewhere between 25 and 50 percent will develop PTS, even though they are anticoagulated.

ADVANCE: Can you tell me about pharmacomechanical catheter-directed thrombolysis (PCDT)?

Well, let's start from the beginning. The reason why people develop PTS in the long run is that the clot remains in the leg and does two things. One is that it continues to block blood flow in the vein and that increases the pressure in the leg. And secondly, the body reacts to the clot by a process called inflammation, and that appears to damage the one-way valves that are present in the vein. So when patients are standing, the veins at the bottom see the full effect of the blood pressure in the vein. That's what causes the problems.

The idea arose many years ago: Why not just remove the clot upfront and thereby prevent those problems?

There are a lot of studies suggesting that if you remove the clot early you will prevent the long-term problems. A number of different methods have been tried over the years to do that. One is what's called surgical thrombectomy, which is basically when a surgeon will do pretty major surgery to cut open the vein and take out the clot. Another method is known as systemic thrombolysis. Thrombolysis refers to the administration of a clot-busting drug, like tissue plasminogen activator (TPA), for example. People used to deliver TPA into the arm veins through a regular IV to try and dissolve the clot, but the downside is that TPA is associated with bleeding. When you inject it into the arm veins, you have to inject a massive dose in order to get enough penetration to do anything to the clot. You don't really get a great result on the clot and you give a significant dose of TPA, and that puts patient at risk for bleeding complications.

Over the last 15 years or so, interventional radiologists have developed a method known as catheter-directed thrombolysis, whereby we infuse these clot-busting drugs directly into the clot. In other words, we place a catheter using image guidance into the clot, and the catheter, which is a lot like a garden hose that has multiple side holes throughout, infuses the drugs into the clot. People began doing that in the early 1990s. That does indeed remove the clot a lot better than the previous method of just injecting the stuff into the arm. The downside is that it still takes a couple days to fully dissolve a DVT, during which time the patient gets a pretty significant dose of the TPA. Also, the patient has to be monitored in the intensive care unit, which involves hospital resources that are important and precious, and there were still bleeding complications. Not as many, perhaps, as with the systemic thrombolysis technique, but still pretty significant.

Finally, the most recent technique we've been using is this thing called pharmacomechanical catheter-directed thrombolysis (PCDT). What that refers to is the combination of the clot-busting drug and the use of the catheter-based device, which can either suck out or macerate, meaning grind up, the clot to get a more efficient treatment. Nowadays we can remove the clot using a combination of the drug and the device much faster than before, and very often in a single procedure session lasting a couple of hours. That's quite a big difference. The idea is that you can also use a lower dose of the thrombolytic drug and thereby make it a safer procedure.

Deep vein thrombosis, caused by a blood clot in the leg, can lead to pulmonary embolism or post-thrombolytic syndrome. courtesy SIR

The number one complication is bleeding. Anytime you give a thrombolytic drug, there's a significant risk of bleeding. Anytime you do a procedure, there's always a small risk of causing injury to the vein or introducing an infection, but those things are quite uncommon. There is also the risk of knocking off clot and having it move to the lungs-a pulmonary embolism.

I would say that the two main potential complications are bleeding and pulmonary embolism, but both of them we would expect to be quite uncommon.

ADVANCE: Is PCDT image-guided? What modality is used?

We use ultrasound primarily to introduce a catheter into the vein, and then we use fluoroscopy, or regular X-rays, to do venograms that show us where the clot is located in the vein. We do the clot removal under fluoroscopic guidance.

ADVANCE: What is the interventional technologist's role in PCDT?

The technologist has a very important role to play in a number of ways, primarily in understanding the general approach to the procedure and being able to set up and provide the equipment, mainly the devices. It's important when you're dealing with clot, because any manipulation you perform in the venous system removes the clot, on the one hand, but on the other hand you rev up the body's natural clotting processes just by irritating the system. What that means is that you really want to make sure your treatments are targeted and as efficient as possible. It helps tremendously to have technologists be an asset to the procedure.

In other words, technologists are expected to follow along and understand what is needed next during the procedure. Some of the devices we use require the technologists to set them up, and it's important for that to be done promptly and efficiently so that we don't waste a lot of time and diminish our therapeutic results.

ADVANCE: Why do you think pharmacomechanical catheter-directed thrombolysis for DVT is underused by physicians?

While you might think that FDA approval and how often something is used would be linked, the reality is that they actually aren't linked that tightly. The reason why [PCDT is] not FDA approved for this indication largely relates to business considerations on the part of the companies that produce the drugs.

In terms of why the clot-removing procedures aren't used as commonly, the number one reason is the risk of bleeding with the use of the thrombolytic drug. Number two, which is sort of linked, is the fact that even though there is a lot of suggested evidence from small studies of systemic thrombolysis and surgical thrombectomy that removing clot will make a difference in the long run, there has never been a large scale, multi-center, randomized trial to really prove that if you do this you will actually make a difference in the PTS two years out, for example. Given that there are safety risks, and given that you're taking people that would have been treated as outpatients and you're putting them through an invasive procedure that uses hospital resources, I think the medical community has said, "Wait a second; we're not ready to do this in all these patients. We'd like to see some proof that this makes a difference and that this procedure makes a difference."

ADVANCE: How do you educate patients and other healthcare professionals about this treatment?

For healthcare professionals, there are a number of venues in which we will be speaking about the procedures. A couple things are important to note. One is that just this year, the American College of Chest Physicians, which provides guidelines on the standard treatment of DVT, changed its recommendations on PCDT to be more neutral. Previously they were very much against it. That has opened the door and increased some awareness in the medical communities as to the use of these procedures.

Just the fact that there is a big trial that's finally going to answer this very controversial question is in itself noteworthy to the medical community. The people that are involved in the ATTRACT trial aren't just radiologists that are trying to advance the use of a radiology procedure. The ATTRACT steering committee includes surgeons, cardiologists, pulmonary medicine specialists, hematologists, a biostatistician and a health economist. It's really a true multidisciplinary research effort. The investigator network includes about 150 physicians from all walks of medicine-emergency, internal, surgery, radiology. When it comes to really influencing physician opinion, it's a hard thing to do as one person from one subspecialty. When you have really a truly broad-based, inclusive network, then you have a much better chance to achieve the kind of education you want.

The other thing I think is important is the fact that we have endorsements from some important medical organizations. The American College of Phlebology, the American Venous Forum and the Society of Interventional Radiology's Foundation have all endorsed the trial. We have a lot of national awareness, and that will help to educate the healthcare community.

In terms of patients, it's a little bit more challenging, because information has to be provided to patients in a different way. It has to be done in accordance with IRB (Institutional Review Board) regulations, and even then, with all the other health information that people are deluged with every day, it's not always easy to get your particular message through. At the treatment centers that are going to be participating in the trial, patients with DVT will be routinely approached and told what PTS is and why it might be worthwhile for them to participate in the study.

ADVANCE: If the ATTRACT trial has positive results, do you think there will be a revolution in the treatment of DVT?

I think this would really produce a big paradigm shift. The use of blood thinners became routine for DVT and PE around 1960. Since 1960, there have been some modifications to the way we deliver the blood thinners, but really we're using more or less the same drugs, and it's basically the same approach: Somebody has a blood clot, so prevent the next episode and prevent PE by giving them a blood thinner. If this trial were to be positive, it would really provide a major paradigm shift to say, you know what? You don't just need to prevent the next episode with the blood thinner, you need to actually remove the clot now. That's what's going to help the patient two, three, four, five years down the line. I think that would drive the development of even better drugs and devices and healthcare systems to enable us to tackle DVT in a way that may be better for patients' long-term health.

The results of the trial will probably be out in around five years. We look at it as investigators; we're going to do a very careful investigation. People on the research team are both proponents and skeptics, and I think that's what will create the healthiest research environment. If results are positive, it would really make a big difference and would enable us to help many, many patients and prevent them from having terrible problems.

Heather Simons is editorial assistant at ADVANCE. She can be reached at hsimons@advanceweb.com.