Ultrasound-Accelerated Thrombolysis: IRs Examine This Promising Treatment Option
By Bob Croce
Vol. 15 No. 12 P. 16
Many interventional radiologists say that they will take a wait-and-see approach toward considering ultrasound-accelerated thrombolysis (UAT) to be a better alternative to treat blood clots than catheter-directed thrombolysis (CDT) in the peripheral vasculature. The belief is that the promising treatment requires further prospective research before it may replace CDT.
UAT uses high-frequency, low-power ultrasound delivered through a specialized catheter, along with thrombolytic drugs, directly into the blockage. The objective is for those ultrasound waves to accelerate the penetration of the thrombolytic drugs into the clot and hasten its breakup. The catheter and infusion system are manufactured by EKOS Corporation.
A recent retrospective study conducted by Baptist Health South Florida and released in the Journal of Vascular and Interventional Radiology in August, found no significant difference in outcomes after examining the medical records of 102 patients who underwent either UAT or CDT for acute and subacute limb ischemia between August 2005 and January 2012. The noninferiority study showed slightly fewer incidents of minor or severe bleeding with UAT, but the researchers concluded that "both UAT and CDT are safe and efficient treatment modalities."
Outcomes and Cost
The interventional radiologists who spoke with Radiology Today haven't ruled out UAT becoming the therapy standard in the future. The issue, they say, is that more research is needed to confirm better outcomes relative to CDT and/or to show lower overall cost, largely through shorter treatment times and delivering less medication, to justify the investment in the new technology and the catheters.
"I think ultrasound-accelerated thrombolysis has the potential to become the standard, but the question of the day is whether it's now time to do a prospective, randomized trial comparing the two therapies," says Robert Lookstein, MD, a specialist in vascular and interventional radiology at Mount Sinai Medical Center in New York.
"We also need to look at not only the patient-centric factors, but also the economic factors. In the end, we need to determine if there is enough of a [patient] safety effect to warrant the increase in cost. I don't think that question has been answered yet," he adds.
Although the Baptist Health study didn't take treatment time into account, clearly this has become an area of interest in UAT. Lookstein says some CDT treatments can take 24 hours to complete, while it could take as few as eight hours with UAT. A study conducted in the Netherlands in 2011 found that using UAT over CDT cut average treatment time by 12 hours, which in turn also cut costs by reducing the time needed for the administering of thrombolytic drugs. Shorter treatment times might also translate to better patient outcomes as well as a good return on investment for hospitals.
"If you could get into a situation where it's a single session, almost as ambulatory surgery, that would be a good thing," Lookstein says, "not only from an improved patient safety standpoint, but it would be a tremendous economic benefit to the patient and to the hospital."
But the higher cost of the new technology could be a deterrent if it doesn't produce better outcomes. That's one reason why organizations are looking for a prospective trial to learn whether UAT creates better patient outcomes that might justify switching from CDT, Lookstein adds.
When it comes to patient outcomes, another interesting finding from the Baptist study does slightly favor UAT: Of the medical records examined by Baptist, complete lysis was achieved by 72% of the patients who had UAT, as opposed to 63% who had CDT.
The evidence suggesting shorter treatment time, less bleeding, and better lysis of clots requires more research to support those findings, radiologists say.
Shorter Treatment Time
"From a patient standpoint, anytime a new technology has the potential to decrease therapy time, or time needed to be in the hospital, that's obviously of great benefit to a patient," says Sanjay Misra, MD, an interventional radiologist at the Mayo Clinic in Rochester, Minnesota, where both CDT and UAT are performed. "We just need to see more data through additional trials.
"The data is promising, but we need more research. We're doing a funded trial in May, and we may get some early signals [on its effectiveness] in the veins," says Misra, who is confident that UAT will become the standard in treating acute and subacute limb ischemia. "But that trial won't be completed for two years. If that trial is suggestive, maybe we'll get a head-to-head trial in the arteries. We're confident we'll get some data that will build on what we already know."
Radiologists see shorter treatment time and fewer incidents of minor or severe bleeding as the biggest potential advantages of using UAT over CDT. Even though the difference in bleeding discovered in the Baptist study findings were not overwhelmingly in favor of UAT, researchers there still feel the data is significant.
Although authors of the Baptist Health study caution that their findings around reduced bleeding "warrant [future] prospective comparative trials," they also feel that less incidence of bleeding is a solid checkmark in the column favoring UAT as a treatment option.
"It [less incidence of bleeding] was still a statistically significant number," says Shaun Samuels, MD, who worked on the study with Baptist radiologists Melanie Schernthaner, MD; Peter Biegler, MD; James Benenati, MD; and Heiko Uthoff, MD.
"We could try to drill down on the reason for that [less bleeding], but the fact is that is what we found. For that reason alone, I could definitely recommend the procedure," says Samuels, who adds that he feels strongly that the findings of the Baptist study have significant value, even though the research conducted had some limitations.
The sample from Baptist, which has for several years been a leading-edge learning environment for UAT, included some older cases in which CDT was performed on a slightly different procedural basis than it is today. Because it was a retrospective study, there were other variables that the researchers couldn't control. The findings were based on the medical records of 75 patients who underwent UAT and 27 patients who received CDT.
"I think the data on bleeding is interesting, but we also need more research since certain genes in different people make them clot off more, and certain genes make you predisposed to bleeding," Misra says. "This makes it really hard to look at bleeding here."
Even so, Samuels and other interventional radiologists feel the study is a good starting point. Until additional questions are answered, though, radiologists feel that most health care organizations won't risk the capital expense necessary to upgrade to UAT.
"There will always be a place for catheter-directed thrombolysis, but more and more I sense that UAT will replace CDT, and CDT will become sort of a niche application," Samuels says. With more to be learned, Samuels says he already believes that UAT is a better treatment option.
From a procedural standpoint, Samuels says the setup of the catheters between UAT and CDT are "reasonably similar." The difference is that UAT requires "a 6 French catheter, which is a larger caliber catheter than is used for conventional CDT," he adds. "That means you are obligated to put in a larger access. Whether that makes any difference in terms of complications, our study wasn't empowered to tell. But [even with the larger catheter] it is interesting that bleeding was less."
Samuels also feels that the UAT system is "slightly" more complicated from the standpoint that there are more plug-ins and more cords, and that it allows for a little less flexibility when it comes to treatment technique. But these really aren't "prohibitive challenges," he says.
Considering the findings of the studies by Baptist and others, and a move now toward additional trials, every physician we interviewed agreed that UAT is likely to pass muster with clinicians as a safe and effective treatment option. But if the findings continue to show that UAT and CDT are similarly effective, the issue becomes return on investment, the physicians add.
Although it's every health care provider's primary goal to provide the best care possible, "it definitely comes down to cost," Lookstein says. "The new device is definitely more expensive than the traditional catheter-directed thrombolysis. It requires a capital expenditure. Disposables are more expensive and slightly more labor intensive to set up, but the fact that the device cuts down on length of procedure time obviously weighs in here too."
"So far," Misra says, "our experience with UAT and other data suggests that the combination of ultrasound waves and clot-reducing drugs will penetrate the thrombus better. We're hopeful, but now we just need further proof through a prospective trial. Is it safer? In the long run, is it cheaper? That's what we'll find out."
— Bob Croce is a freelance health care writer based in the Boston area.