Patients who underwent ultrasound-facilitated, catheter-directed fibrinolysis for acute pulmonary embolism (PE) had significantly better outcomes than those who received standard systemic anticoagulants, according to a study presented today at the American College of Cardiology’s Annual Scientific Session (ACC.26; 28–30 March, New Orleans, USA). The targeted catheter-based approach reduced early PE-related death, circulatory collapse or PE recurrence by more than 60%.
HI-PEITHO is the first trial to directly compare clinical outcomes from a catheter-based strategy versus systemic anticoagulation alone in patients with elevated-risk forms of PE. The study was published online in the New England Journal of Medicine at the time of presentation at ACC.26.
“This trial shows that a catheter intervention can indeed be effective and improve the prognosis for patients with severe PE and elevated risk of early death or life-threatening complications,” said Stavros V Konstantinides (University Medical Center of the Johannes Gutenberg University, Mainz, Germany), the study’s lead author. “If the right patients are selected for this procedure, it can prevent patients from deteriorating and it can do so at an acceptably low risk of bleeding complications.”
The trial enrolled 544 patients at 59 sites in the USA and eight European countries (Austria, France, Germany, Ireland, Poland, Switzerland, the Netherlands and the UK). Participants had intermediate-risk PE with two additional indicators of clinical severity, including: tachycardia, low blood pressure (although not at a level indicating shock) and/or low oxygen saturation. Half of the patients were randomly assigned to ultrasound-facilitated catheter-directed thrombolysis, and the other half received standard systemic anticoagulation. Physicians used standardised protocols for administering the study medications in both treatment arms, and they also followed standard protocols for initiating rescue treatment if patients suffered cardiorespiratory decompensation or a repeat PE.
At 30 days, 4% of those in the catheter-based treatment group and 10.3% of those in the control group experienced the trial’s primary composite endpoint of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic PE recurrence within seven days of randomisation. The 61% between-group difference was significant in favour of the catheter-based treatment arm and was driven by a reduction in the rate of cardiorespiratory decompensation or collapse in this group. No brain bleeds occurred, and there were few deaths in either study arm; the results showed no significant difference in deaths of any cause or in major bleeding complications between groups.
Researchers said that the ultrasound-facilitated catheter-directed thrombolysis approach used in the study is feasible to perform for physicians experienced in cardiovascular interventions and in hospitals that are equipped with a catheterisation lab and a team qualified to support the procedure around the clock.
“The results regarding effectiveness are very convincing,” Konstantinides said. “In addition, the study offers a precedent for how to evaluate the effects of catheter treatments for PE. There are many types of catheter treatment, and as more trials are conducted, we hope that we will have increasingly strong evidence to inform guidelines on what strategies to recommend.”
Researchers are currently tracking patient outcomes up to 12 months to assess potential differences in long-term survival, late complications, functional outcomes, quality of life and healthcare utilisation. They said the results might differ in ethnologically more diverse populations, and that the study was not powered to exclude potential differences in bleeding risk between groups. They also said the study results should not be extrapolated to apply to all catheter-based PE treatment approaches, which include a wide range of devices and methods.
The recently published American Cardiology (ACC)/American Heart Association (AHA) guideline for the evaluation and management of acute PE in adults establishes a new clinical classification system to assess PE severity and guide treatment strategies.
The HI-PEITHO trial was an investigator-initiated study funded by Boston Scientific and conducted in partnership with the University Medical Center Mainz in Germany and the PERT Consortium in the USA.
“The real value lies in individualised care”: The vascular community react to HI-PEITHO
Speaking to Venous News, several voices weighed in on the significance of the HI-PEITHO trial data:
David Dexter (Sentara Vascular Specialists, Norfolk, USA) said: “Finally, in the world of randomised controlled trials [RCTs], comparing intervention to anticoagulation, we see a decompensation advantage. Most of our data to date on anticoagulation versus intervention have been on safety and long-term follow-up, but not in terms of true mortality advantage. So, seeing this through the prism of a 500-plus-strong RCT is a giant big deal.
“More data is coming in the PE space, including the nearly complete PE-TRACT, putting a real hold on the new guidelines. The guidelines suggest intervention in categories E and D2—and at least categories C3 and D1 are somewhat questionable—and now HI-PEITHO starts to answer that question to say: ‘Hey, maybe in what we used to call intermediate-high and now intermediate-high with normotensive shock or short-term hypotension, we’re going to see a real mortality and decompensation advantage with early intervention.'”
Nicolas Mouawad (McLaren Health, Bay City, USA) commented: “The data were long-awaited, most rigorous and, crucially, from a global RCT spanning Europe and North America. The goal has always been, what should we do with patients with intermediate-risk PE? That was an unmet answer. Is intervention important, or is anticoagulation the correct answer? And there was equipoise in this moving forward; there was no real answer. So, this is the first RCT—global—in over 500 patients showing that intervention with thrombolytic therapy plus anticoagulation did better than anticoagulation alone.”
Joseph Liechty (Texas Vascular Associates, Frisco, USA) shared: “The trial very clearly delineated two arms of patients and who to treat, seeing a great outcome with thrombolytics. Now, there are so many thrombectomy devices and so many ways to treat PE, having individual studies that look at the effectiveness of each device is probably the right place to start.”
“The thing everybody would love to see is a randomised trial where, once you decide the patient needs an intervention—most people don’t need to be convinced an intervention is going to help the sickest people—the question is then: which device? Which one gets you better faster and which one has the fewest complications while you’re still admitted, and which one requires the fewest reinterventions, which one is the most cost effective?”
Patrick Muck (TriHealth, Cincinnati, USA) said: “The trial’s importance is amplified by the evidence it adds to a growing body showing that embolus removal or dissolution is helpful for patients. This Boston Scientific collaboration with the PERT Consortium is only going to increase our knowledge of that disease process, how to treat it and how to increase patient survival in folks who suffer from pulmonary embolism.”
Raghu Kolluri (OhioHealth, Columbus, USA) said: “The HI-PEITHO results represent a meaningful step forward in refining the management of intermediate-high-risk PE. The signal toward reduction in clinical deterioration with catheter-based therapy is very encouraging. The trial once again highlights that the real value lies in individualised care.”
Marianne Brodmann (Medical University of Graz, Graz, Austria) stated: “Even if we are now able to achieve good results with large-bore thrombectomy devices, we still miss the narrower branches in the pulmonary arteries when it comes to clot removal. So, the addition of local thrombolytic therapy is a valid and necessary approach.”
