NEW ORLEANS – A major advance for the treatment of intermediate-risk pulmonary embolism (PE) has come with HI-PEITHO’s landmark report on ultrasound-facilitated, catheter-directed thrombolysis (CDT).
In this difficult-to-treat group of acute PE patients, the composite endpoint of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of PE within 7 days significantly favored individuals who received CDT as opposed to anticoagulation alone (4.0% vs. 10.3%, RR 0.39, 95% CI 0.20–0.77).
The benefit of CDT administered in the study, particularly with alteplase delivered by the EKOS+ endovascular device, was clearly driven by a reduction in cardiorespiratory decompensation or warning signs of collapse in the intervention group, Stavros Constantinides, MD, of the University Medical Center Mainz in Germany, reported at the annual meeting of the American College of Cardiology (ACC).
HI-PEITHO was published simultaneously New England Journal of Medicine.
Importantly, safety also emerged in EKOS+ CDT and HI-PEITHOS between the control groups, whether in terms of major bleeding at 7 days (4.1% vs. 2.2%, P=0.32), major bleeding at 30 days (4.1% vs 3.0%, P=0.64), or intracranial hemorrhage at 30 days (0 for both). One ischemic stroke occurred in the intervention group (vs 0 with control) but this did not reach statistical significance.
“I think this is a really big day for the field of RCTs (randomized clinical trials) and PE,” commented Jay Giri, MD, MPH, of the University of Pennsylvania in Philadelphia. “For 15 years, we have had a hypothesis that by delivering the lytic locally with a much lower dose, we could maintain efficacy but reduce the risks of complications, bleeding.”
“(HI-PEITHO) is a very exciting trial, I would say the most important trial in patients hospitalized with PE in the last 12 years since the original PEITHO trial,” said Giri, who was not involved in the study. Medpage Today.
Patients selected for HI-PEITHO were in the intermediate-to-high-risk group who appeared stable but had some evidence of right ventricular dysfunction and were at risk for cardiorespiratory decompensation – a group long considered a difficult gray area to treat. Original in 2014 Peitho Trials, for example, of systemic, full-dose tenecteplase in the intermediate-risk setting had mixed results: it successfully prevented hemodynamic decompensation, albeit at the cost of additional major bleeding.
Meanwhile, EKOS+ and various catheter-based PE interventions have already reached the US market.
“Before[high-risk]there was insufficient data to support the CDT for this group and physicians were left to their best judgment on how to intervene. “Clinicians would be more willing to use advanced measures in[high-risk patients]because these patients may already be showing signs of cardiopulmonary insufficiency or collapse,” explains Mark Krieger, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire. Are.”
Essentially, by going the CDT route in HI-PEITHO, Constantinides and colleagues were able to replicate the PEITHO benefit while producing a lower risk of major bleeding.
Nevertheless, the clinical benefit observed in this trial may still be a source of controversy.
Giri highlighted the test’s reliance on the National Early Warning Score (NEWS), in which various points are scored for abnormal respiratory rate, oxygen saturation, use of supplemental oxygen, body temperature, systolic blood pressure (BP), heart rate and level of consciousness. This is a criterion for cardiorespiratory decompensation or collapse, which is not familiar to many people in clinical practice, who ultimately became HI-PEITHO positive.
Then there is also the argument that cardiovascular decompensation itself is not a patient-oriented outcome. “There was no significant difference in death, recurrent PE, or even a 6-minute walk at 30 days, which indicates functional status,” cautions Lauren Westfer, DO, MPH, of UMass Chan Medical School-Baystate in Springfield, Massachusetts, who was not involved in the study.
Giri pointed out two other caveats, namely that the patients included had an inherently low bleeding risk, and that this was a population affluent at risk. “It’s not that every patient is coming in with right ventricular dysfunction,” he said. “If we’re going to expand the therapy to slightly healthier patients, this trial is not necessarily telling us to do that, so I think we have to think about it more carefully.”
Still, “this is what we call the real beginning of the golden age of pulmonary embolism RCTs,” he said. He cited ongoing CDT trials in intermediate-risk PE. Prague-26 And pe-tractas well as his group’s mechanical thrombectomy trial Unique II.
study details
HI-PEITHO was a postmarket, open-label trial that examined patients in the US and Europe from 2021-2025. The investigators looked for individuals with intermediate-risk PE who had at least two indicators of cardiorespiratory distress (eg, systolic BP ≤110 mm Hg; heart rate ≥100 beats per minute, or respiratory rate >20 breaths per minute). Patients with persistent hemodynamic instability were excluded.
Notably, this arguably places HI-PEITHO patients somewhere between C3 and D2 New acute PE diagnostic categories.
The intention-to-treat analysis of the trial included a total of 544 patients (mean age 58.2, 42.6% women) who were randomized to anticoagulation with alteplase with or without ultrasound-facilitated, catheter-guided fibrinolysis.
As part of the primary outcome, cardiorespiratory decompensation or collapse was defined as a person requiring cardiac arrest/CPR, symptoms of shock, ECMO, intubation or non-invasive mechanical ventilation initiation, or reaching NEWS ≥9.
Unfractionated heparin was the most commonly used anticoagulant (71.6% of the EKOS+ group and 55.7% of controls), followed by low molecular weight heparin (50.6% and 53.9%, respectively). “It remains to be seen whether the results will be consistent with more effective and safer anticoagulants,” Westfer said. Medpage Today In an email.
The study authors reported that the intervention group received an average total alteplase dose of 8.9 mg for the 20 patients who had catheter placement on only one side, and 16.9 mg for the vast majority who had catheter placement in both the right and left pulmonary arteries.
Of note, the average total infusion duration was 7.2 hours – a huge strain on resources. According to Westfer, “Health systems and physicians must weigh the increased resource utilization (procedural costs and increased ICU admissions) against the potential benefit, which may be of marginal clinical significance.”
