The treatment of intermediate-risk pulmonary embolism (PE) continues to be an area of therapeutic uncertainty. The initial PEITHO study (2014) demonstrated a reduction in hemodynamic deterioration with systemic thrombolysis, at the cost of a significant increase in stroke and major bleeding. Since then, there has been sustained interest in more localized reperfusion strategies that may improve the safety profile.
The objective of the HI-PEITHO study was to evaluate whether ultrasound-facilitated catheter-directed thrombolysis (USCDT) with the EKOS system, combined with anticoagulation (AC), could improve clinical outcomes compared with AC alone (LMWH or UFH according to local protocols) in patients with intermediate-risk acute PE.
This was a multicenter, open-label, parallel-group study. A total of 544 patients were enrolled across 59 centers in the United States and Europe. The main inclusion criteria were age between 18 and 80 years, acute PE confirmed by CT angiography, RV/LV ratio ≥1.0, elevated troponin, and cardiorespiratory distress, while patients with hemodynamic instability were excluded.
Patients were randomized to USCDT + AC or AC alone. In the interventional arm, alteplase was administered at a dose of 9 mg per catheter, with a mean infusion duration of 7.2 hours, in combination with AC. The primary endpoint was a 7-day composite of PE-related mortality, PE recurrence, or cardiorespiratory decompensation/collapse.
The results showed a significant reduction in the primary endpoint in the USCDT group: 4.0% vs 10.3%, with a relative risk of 0.39 (p=0.005). The need for rescue therapy was also lower with the interventional strategy (2.9% vs 9.2%). Notably, 78.8% of patients requiring rescue therapy had previously met criteria for decompensation or cardiorespiratory collapse (according to NEWS score).
Regarding safety, no significant differences in major bleeding were observed between groups. Major bleeding according to ISTH criteria at 7 days was 4.1% with USCDT vs 2.2% with AC alone (p=0.32), while at 30 days it was 4.1% vs 3.0% (p=0.64). In addition, no intracranial hemorrhages were reported in either group up to 30 days. No relevant differences were observed in 30-day events, with all-cause mortality of 1.8% vs 1.1%, symptomatic recurrence of 0.4% vs 0.7%, and serious adverse events of 14.8% vs 16.2%.
Conclusions: HI-PEITHO Study Design: EKOS catheter-directed thrombolysis plus anticoagulation vs anticoagulation alone in intermediate-risk PE
In patients with intermediate-risk acute PE, USCDT reduced the composite endpoint of PE-related mortality, cardiorespiratory decompensation or collapse, and symptomatic PE recurrence at 7 days compared with anticoagulation alone, without significant differences in major bleeding complications.
Presented by Stavros V. Konstantinides at the Late-Breaking Clinical Trials, ACC.26, March 28–30, New Orleans, USA.
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