PRAGUE-26: Catheter-Directed Thrombolysis Beneficial in Intermediate-High-Risk PE

Presentation ESC 2026

Discussant review: PRAGUE-26

MUNICH, Germany—Patients with intermediate-high-risk acute pulmonary embolism (PE) have better outcomes if they receive not only standard anticoagulation therapy, but also catheter-directed thrombolysis with alteplase, results from the PRAGUE-26 trial show.

The study’s primary endpoint of all-cause death, recurrent PE, or cardiorespiratory decompensation or collapse within 7 days was a relative 90% lower with the addition of thrombolysis, Viktor Kočka, MD, PhD (University Hospital Královské Vinohrady, Prague, Czechia), reported at the recent European Society of Cardiology (ESC) Congress 2026. The results were simultaneously published in the New England Journal of Medicine with Josef Kroupa, MD, PhD (University Hospital Královské Vinohrady), as first author.

“Pulmonary embolism is common and carries a significant in-hospital mortality,” in the range of 11% for patients treated in a standard ward and 23% for those treated in the intensive care unit, said Kočka. “The vast majority of patients are managed, even now, in the same way as they were managed 30 years ago—that is, anticoagulation and systemic thrombolysis if the patient crashes.”

This stands in stark contrast to the progress made in the management of acute stroke and STEMI, he added. “The unmet clinical need in PE is large.”

PRAGUE-26 joins PEERLESS, HI-PEITHO, and STORM-PE as one of the few randomized trials to look at acute PE management. Catheter-directed thrombolysis in intermediate-risk PE was the focus of both HI-PEITHO (EkoSonic; Boston Scientific), where it was compared with anticoagulation alone, and PEERLESS, where it served as the comparator against mechanical thrombectomy (FlowTriever; Inari Medical). STORM-PE assessed mechanical thrombectomy (Lightning Flash; Penumbra) versus anticoagulation alone in acute intermediate-high-risk PE.

However, unlike the ultrasound-guided approach captured in PEERLESS and HI-PEITHO, the PRAGUE-26 trial used “standard catheter-directed thrombolysis,” Kočka said.

The latter method “is a standard right-heart catheterization with over-the-wire advancement of an infusion catheter into each pulmonary artery. Then a 1-mg bolus of alteplase is given, followed by 1-mg/hour infusion lasting for 9 hours, with the total dose reaching 20 mg of alteplase for bilateral PE,” he explained. “No specialized equipment or training is required.”

At a press conference, Kočka reiterated the feasibility of the method. “This is a simple procedure that any interventional cardiologist worldwide can do easily, and it does use the existing cath lab infrastructure. It has a short learning curve,” he stressed.

PRAGUE-26

At 11 Czech tertiary care centers, PRAGUE-26 investigators enrolled 558 patients (median age 64 years; 40.9% were female) with intermediate-high-risk acute pulmonary embolism, defined by hemodynamic stability, a simplified Pulmonary Embolism Severity Index score of ≥ 1, and right ventricular dysfunction plus an elevated level of cardiac troponin or natriuretic peptide. Around half presented directly, with the remainder being transferred from referring hospitals. Study participants were randomized, in an open-label fashion, to receive anticoagulation therapy with or without the addition of catheter-directed thrombolysis with alteplase.

At 24 hours, the median right-to-left ventricular ratio on transthoracic echocardiography was 0.94 in the thrombolysis group and 1.07 in the standard-care group. 

A primary-outcome event occurred within 7 days in two patients (0.7%) assigned to thrombolysis and 19 patients (6.8%) assigned to standard care (relative risk [RR] 0.10; 95% CI 0.02-0.44). The difference was mainly due to the thrombolysis group having a lower incidence of cardiorespiratory decompensation or collapse (0.7% vs 5.4%; RR 0.13; 95% CI 0.03-0.57). Results were consistent across subgroups.

PE recurrence rates were 0.7% and 0.4%, respectively, representing a nonsignificant difference. In the first 7 days, four patients randomized to standard care died. Between days 8 and 30, one patient randomized to thrombolysis died.

“Mortality in the trial population was very low. This finding may reflect close monitoring within the trial environment, as well as the tertiary care setting, where there was immediate access to rescue reperfusion therapy,” the authors note in NEJM.

“However, a substantial proportion of patients with pulmonary embolism are treated in smaller regional hospitals, where cardiorespiratory decompensation may be associated with increased mortality,” they add. “In this context, prevention of cardiorespiratory decompensation or collapse may represent a clinically meaningful treatment effect, although further study is needed to confirm this hypothesis.”

This is a simple procedure that any interventional cardiologist worldwide can do easily. Viktor Kočka

Additionally, rates of BARC-defined clinically relevant bleeding were similar in the thrombolysis and anticoagulation alone groups (4.6% vs 5.0%; P = 0.85), as were the rates of GUSTO-defined major bleeding (1.4% vs 2.2%; P = 0.54), intracranial hemorrhage (0.7% vs 0; P = 0.50), and ischemic stroke (0 vs 0.4%; P = 0.50).

Median times from admission to discharge from the ICU were 2.1 days with thrombolysis and 2.8 days with anticoagulation alone, while the median hospital stays were 4.3 and 5.1 days, respectively. None of the patients randomized to thrombolysis experienced failure of their first-line therapy, as compared with 12 (4.3%) of those randomized to standard care.

Irene M. Lang, MD (Medical University of Vienna, Austria), the discussant for PRAGUE-26, said the rationale for PRAGUE-26 is clear. “Systemic thrombolysis in intermediate-high-risk pulmonary embolism is efficacious, but it is not safe,” in that it ups bleeding risk, she said, citing the 2014 PEITHO trial. 

In line with the more recent HI-PEITHO, however, the new study demonstrates the safety of the catheter-directed intervention, Lang continued. Despite some differences between the two trials, “PRAGUE-26 is a confirmation of HI-PEITHO, and it is an academic study that’s very valuable for patients, because it’s not driven by any interests,” she said.

What PRAGUE-26 doesn’t show, added Lang, is that ultrasound isn’t needed, since the trial was not designed to test that question. Moreover, she stressed that it’s necessary to wait on the forthcoming PEITHO-3 trial results “before we can definitely advertise catheter-directed thrombolysis as the primary treatment of intermediate-high-risk PE.”

How to Organize Care?

The investigators note in their paper that “wider access to interventional treatment for pulmonary embolism might be facilitated by adapting established regional networks and transfer pathways that are already used in the treatment of patients with ST-segment elevation myocardial infarction.”

In Europe, Kočka highlighted, new PE guidelines are expected in 2027.

Carlos Aguiar, MD (Hospital Santa Cruz, Lisbon, Portugal), who chaired the ESC media briefing, said that beyond clinical recommendations, the guidelines will help national policies move forward. “What implications does this [trial] have for the way we organize care for these patients?” he asked, referencing the success of STEMI networks in driving the adoption of primary PCI. “I think now we’re moving into an era where clearly the best treatment for these intermediate-risk patients, which is a large patient group, is interventional and so we’re going to need to structure that care.”

Kočka noted that so far this population has been “neglected” in this regard. “We’re used to cardiac patients being in cardiology wards, but patients with PE are on the gynecology ward, orthopedic ward, surgical ward, general med ward—they’re all over the hospital,” he said. “We’ve never felt the need to centralize the care because we did not have a lot to offer to them.”

The good news, though, is that existing cath lab infrastructure can now be used for PE, Kočka added. 

In the United States, the pulmonary embolism response team (PERT) model of collaborative, standardized care has taken off over the past decade. Anecdotally, he has the “clear impression” that Europe is behind the United States when it comes to PERTs, Kočka told TCTMD. “We have work to do.”

Aguiar pointed out that while his center in Portugal has a dedicated PE team, many others there do not. “The infrastructure, which is a huge major step that’s already been taken care of, is there, but the organization of people is still not there,” he commented to TCTMD, noting that fortunately the skills involved in catheter-directed thrombolysis are “very simple,” which will allow for change to come quickly.