What Is the EKOS Procedure for Treating Blood Clots?

The EKOS procedure is a catheter-based treatment that uses ultrasound energy alongside a clot-dissolving drug to break up dangerous blood clots, most commonly in the lungs. It is technically known as ultrasound-assisted catheter-directed thrombolysis (UACDT or USCDT), and the device itself is the EkoSonic Endovascular System manufactured by Boston Scientific. The procedure sits in a middle lane between full-dose systemic clot-busting drugs, which carry substantial bleeding risk, and anticoagulation alone, which sometimes cannot resolve a large or life-threatening clot fast enough. Its appeal rests on the idea that adding ultrasound lets doctors use lower doses of the thrombolytic drug while still clearing the clot effectively.

How the Procedure Works

A thin catheter is threaded through a vein, typically starting from a groin or neck access point, and guided into the blood vessel where the clot sits. For pulmonary embolism, the catheter advances through the right side of the heart and into the pulmonary arteries. Once positioned, the catheter serves a dual purpose: it delivers a thrombolytic drug (usually alteplase, a form of tissue plasminogen activator, or tPA) directly into the clot, and it emits low-energy ultrasound waves from tiny transducers built into its tip.

The ultrasound does not physically blast the clot apart. Instead, it loosens the fibrin structure of the clot, making it more porous and easier for the drug to penetrate. Lab research has shown that applying ultrasound alongside tPA achieves similar clot-dissolving efficiency with roughly 25% less drug compared to tPA alone.¹ The rationale is straightforward: less drug in the body means a lower chance of bleeding complications, which is the main danger with any thrombolytic therapy.²

Once the catheter is in place, the drug infusion typically runs for several hours while the patient is monitored in an intensive care unit. Treatment durations in clinical practice have ranged from as little as two hours to overnight sessions, depending on the clot burden and the protocol a hospital follows. After the infusion ends, repeat imaging confirms how much of the clot has dissolved, and the catheter is removed.

Evidence in Pulmonary Embolism

Pulmonary embolism, where a clot lodges in the lung arteries and strains the heart, is the primary condition the EKOS procedure targets. The landmark study here is the ULTIMA trial, a randomized controlled trial that compared ultrasound-assisted catheter-directed thrombolysis with heparin (the standard blood thinner) alone in patients with intermediate-risk PE. These are patients sick enough that the right side of their heart is visibly enlarged from the strain but not yet in full hemodynamic collapse.

The trial measured the ratio of the right ventricle to the left ventricle on imaging, a marker of how much strain the clot is putting on the heart. In the EKOS group, that ratio dropped from about 1.28 to 0.99 within 24 hours, meaning the right ventricle shrank back toward normal size. In the heparin-only group, the ratio barely budged, going from 1.20 to 1.17. The difference was large and statistically clear, and no increase in bleeding complications was observed in the catheter group.³ That result put the EKOS procedure on the map as a tool for intermediate-risk PE, showing it could rapidly unload the right heart in a way that heparin alone could not.

Several subsequent trials, including the SEATTLE II trial and the PERFECT registry, reinforced the picture of clinical effectiveness in this population. These trials, along with the ULTIMA data, form the evidence base that most pulmonary embolism response teams rely on when considering catheter-directed treatment.⁴

Finding the Right Dose and Duration

One of the lingering questions after the early trials was whether doctors could push the drug dose even lower and shorten the time the catheter stays in. The OPTALYSE PE trial tested four different regimens, varying the tPA dose from 4 to 12 milligrams per lung and the infusion time from 2 to 6 hours.⁵ All four arms showed improvement in right heart strain and clot burden, suggesting that even the lowest doses over shorter infusions had meaningful effect.

This matters for practical reasons. A shorter infusion means less time in the ICU, fewer hours of monitoring, and potentially fewer bleeding events. One single-center study found that adopting a shorter-duration, lower-dose protocol cut the median ICU stay from about 3.5 days down to 1 day, with reductions in the need for mechanical breathing or blood pressure support, lower drug costs, and fewer adverse events.⁶ Similarly, a multicenter analysis found that starting EKOS treatment within 12 hours of admission was tied to significantly shorter ICU stays compared to beginning later, with a median of 24 hours versus 45.5 hours.⁷ The general trend in practice has been toward leaner protocols, though there is no single universally adopted regimen yet.

In one institutional experience treating 51 patients with intermediate-high or high-risk PE, a standard protocol of about 11.5 milligrams of alteplase delivered over 15 hours per catheter was used, reflecting a middle ground between the earliest longer protocols and the more aggressive dose-reduction approaches.⁸

Does the Ultrasound Actually Add Anything?

This is the question that makes some interventional cardiologists skeptical, and the evidence here is worth being honest about. The SUNSET sPE trial directly compared the EKOS ultrasound-assisted catheter to a standard multi-hole infusion catheter, with both groups receiving similar doses of tPA for similar durations. The result: clot clearance, measured by a standardized scoring system on CT imaging, was similar between the two groups.⁹

That finding creates an awkward situation: the EKOS catheter costs considerably more than a standard infusion catheter, yet a head-to-head randomized trial found no measurable superiority in thrombus reduction. Proponents argue that SUNSET sPE was a relatively small trial and that the ultrasound component may offer advantages not captured by a single clot-burden score, such as faster onset or the ability to use lower doses safely. Critics respond that the burden of proof lies with the more expensive device, and that trial failed to meet it. For patients and referring physicians, the practical takeaway is that catheter-directed thrombolysis itself is the treatment with the strongest evidence, and whether the ultrasound component adds meaningful benefit over a simpler catheter remains genuinely uncertain.

EKOS Compared to Mechanical Thrombectomy

The other major competitor in the catheter-based PE treatment space is mechanical thrombectomy, where a device physically suctions or fragments the clot rather than dissolving it with drugs. Systems like the FlowTriever and Indigo have gained market share rapidly, in part because they avoid thrombolytic drugs entirely and their associated bleeding risk.

A systematic review and meta-analysis pooling data from dozens of studies and nearly 3,000 patients compared aspiration thrombectomy (mechanical) to EKOS-based thrombolysis. Both approaches had essentially identical technical success rates, above 99%. Thrombectomy procedures took longer on average but resulted in lower blood loss, shorter ICU stays, and shorter overall hospital stays. On the other hand, EKOS showed greater improvement in pulmonary artery pressure and in clot-burden scores.¹⁰

The tradeoff, in plain terms, is that EKOS tends to do a more thorough job of clearing clot and lowering pulmonary pressures, but thrombectomy gets patients out of the ICU and hospital faster and avoids the risks that come with any thrombolytic drug. The choice often depends on the clinical scenario: patients at higher bleeding risk may be better candidates for mechanical thrombectomy, while patients where reducing pulmonary pressures quickly is critical may benefit more from the thrombolytic approach.

On cost, the picture is muddled. One cost-comparison study found that catheter-directed thrombolysis was numerically more expensive than mechanical thrombectomy, but the difference narrowed to a statistically insignificant amount after adjusting for hospital-level variation and when the treatment was performed. The higher raw cost of thrombolysis was driven largely by longer ICU and hospital stays.¹¹

Safety and Bleeding Risk

Bleeding is the primary safety concern with any procedure that involves clot-dissolving drugs. The EKOS procedure uses much lower doses of tPA than systemic thrombolysis (which might give 100 milligrams intravenously), but it is not risk-free. Data from the KNOCOUT PE registry, a large prospective international study of nearly 500 patients treated with ultrasound-facilitated catheter-directed thrombolysis, reported major bleeding within 72 hours in about 1.6% of patients.¹² One patient in that registry experienced worsening of a pre-existing brain bleed after treatment.

Other data sets report somewhat higher bleeding rates. One review cited the largest prospective device trial as showing nearly 10% of patients experiencing major bleeding, though the definitions of “major bleeding” vary across studies and can include events like bleeding at the catheter insertion site that, while classified as major, are less clinically alarming than a brain hemorrhage. That same review noted that the overall risk of intracranial hemorrhage following catheter-directed thrombolysis is estimated at roughly 0.35%.¹³ While rare, intracranial hemorrhage is potentially fatal, and case reports of this outcome exist in the literature.

A retrospective comparison between EKOS-treated patients and those who received systemic alteplase found that major bleeding within 72 hours occurred in about 3.7% of EKOS patients versus 16% in the systemic thrombolysis group, a significant difference favoring the catheter approach. Mortality within six months was also numerically lower in the EKOS group, though the study was not large enough to draw definitive conclusions on that endpoint.¹⁴ The overall picture is that EKOS carries real but substantially lower bleeding risk than full-dose systemic thrombolysis, which is the main safety argument for using a catheter-based approach.

Use Beyond the Lungs

While pulmonary embolism dominates the conversation around EKOS, the device has also been used to treat deep vein thrombosis in the legs and acute limb ischemia, where a clot blocks blood flow to an arm or leg and threatens tissue survival.

In deep vein thrombosis, a small feasibility study found successful thrombolysis in 85% of cases, with complete restoration of blood flow in most patients. No pulmonary embolism occurred during treatment, and only one bleeding event at the catheter insertion site was reported.¹⁵ The goal in DVT is not just to relieve immediate symptoms but to prevent post-thrombotic syndrome, a chronic condition of pain, swelling, and skin changes in the affected leg. Whether catheter-directed thrombolysis truly prevents post-thrombotic syndrome better than blood thinners alone has been debated, and the evidence is not as clear-cut as the PE data.

For acute limb ischemia, the PARES trial tested an earlier version of the ultrasound-enhanced catheter and achieved full clot removal in 88% of patients, using a mean of 17 milligrams of tPA over about 17 hours.¹⁶ A real-world study of 32 patients treated with EKOS for acute limb ischemia found limb salvage rates of about 94% at 30 days and 88% at one year, though adverse limb events continued to accumulate over time.¹⁷

As with pulmonary embolism, the question of whether the ultrasound component adds value over a standard infusion catheter applies here too. A comparison of EKOS versus a standard multi-hole catheter (Uni-Fuse) in 91 patients with acute limb ischemia found no significant differences in infusion duration, tPA dose, technical success rate, limb loss, or complications between the two devices.¹⁸ The 30-day mortality rate was 4% regardless of which catheter was used. These results reinforce the pattern seen in pulmonary embolism: catheter-directed thrombolysis works well, but the ultrasound enhancement has yet to prove it delivers measurably better outcomes than simpler, less expensive catheters.

Who Gets the Procedure and Who Doesn’t

Patient selection is everything with EKOS. For pulmonary embolism, the primary target population is intermediate-high risk patients: those who are hemodynamically stable (their blood pressure has not crashed) but show signs of right heart strain on imaging, elevated cardiac biomarkers, or both. These patients are too sick for just blood thinners but not yet in the kind of cardiovascular collapse that would mandate surgical embolectomy or systemic thrombolysis. Accurately identifying this in-between group requires weighing clinical scores, imaging findings, and lab markers together.¹⁹

Most hospitals that offer EKOS have a pulmonary embolism response team, a multidisciplinary group that convenes quickly when a significant PE is diagnosed. The team reviews the imaging, the patient’s hemodynamics, bleeding risk factors, and any contraindications to thrombolytic drugs, then decides whether catheter-directed therapy, mechanical thrombectomy, systemic lysis, or anticoagulation alone is the best path. Patients with active bleeding, recent surgery, recent stroke, or uncontrolled hypertension are generally poor candidates for any thrombolytic-based approach.

For deep vein thrombosis and limb ischemia, the decision framework is different. In DVT, catheter-directed therapy tends to be reserved for younger patients with extensive clot in the major veins who face a high risk of long-term complications. In limb ischemia, the urgency is more immediate, and the choice between catheter-directed thrombolysis and surgical thrombectomy depends on how threatened the limb is and how quickly blood flow needs to be restored.

Pregnancy and Other Evidence Gaps

One population conspicuously absent from the EKOS evidence base is pregnant women. Every major catheter-directed thrombolysis trial for pulmonary embolism, including ULTIMA, SEATTLE II, PERFECT, and OPTALYSE PE, excluded pregnant patients.²⁰ Pregnancy itself increases the risk of blood clots, and pulmonary embolism remains a leading cause of maternal death, so the gap is not trivial. The few reports of EKOS use in pregnant patients are individual case reports, and there is no established protocol for dosing, duration, or monitoring in this population.

Other understudied groups include patients over 80, those with significant kidney disease (since the contrast dye used in imaging and the catheter procedure itself pose risks), and patients on certain newer anticoagulant medications where the interaction with catheter-directed tPA is not well characterized. The large registries are starting to capture more diverse populations, but for now, the strongest evidence applies to a somewhat narrow slice of patients: middle-aged to older adults with intermediate-risk PE and no major contraindications to thrombolytic drugs. How well the results generalize beyond that group remains an open question that future registries and trials will need to address.