Key Points
- Ultrasound-facilitated, catheter-directed fibrinolysis (USCDT) plus anticoagulation significantly reduced the primary composite endpoint compared with anticoagulation alone (4.0% vs. 10.3%; relative risk 0.39; 95% CI, 0.20–0.77; p=0.005).
- The benefit was primarily driven by a reduction in cardiorespiratory decompensation or collapse (3.7% vs. 10.3%; relative risk 0.40; 95% CI, 0.20–0.70), with no significant difference in mortality or recurrent pulmonary embolism.
- Major bleeding rates were numerically higher but not statistically different between groups at 30 days (4.1% vs. 3.0%; relative risk 1.4; 95% CI, 0.6–3.4; p=0.64), and no intracranial hemorrhage occurred.
Acute pulmonary embolism (PE) remains a leading cause of cardiovascular morbidity and mortality, particularly in patients with intermediate-risk disease characterized by right ventricular dysfunction and elevated biomarkers. While systemic fibrinolysis reduces hemodynamic collapse, its use has been limited by bleeding risk. The HI-PEITHO trial (NCT04790370) was designed to evaluate whether ultrasound-facilitated, catheter-directed fibrinolysis using low-dose alteplase could improve clinical outcomes while mitigating bleeding risk in this population. The trial was published in New England Journal of Medicine simultaneously.
HI-PEITHO was a multinational, randomized, open-label trial sponsored by Boston Scientific, with blind endpoint adjudication that enrolled 544 patients with acute intermediate-risk PE across 59 sites. Patients were randomized 1:1 to receive USCDT plus anticoagulation (n=273) or anticoagulation alone (n=271). The primary endpoint was a composite of PE-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of PE within 7 days.
At 7 days, the primary composite outcome occurred in 11 patients (4.0%; 95% CI, 2.3–7.1) in the USCDT group compared with 28 patients (10.3%; 95% CI, 7.2–14.5) in the anticoagulation-alone group (relative risk 0.39; 95% CI, 0.20–0.77; p=0.005). This effect was largely driven by a reduction in cardiorespiratory decompensation or collapse (3.7% vs. 10.3%; relative risk 0.40; 95% CI, 0.20–0.70). Rates of PE-related death were low and not significantly different (1.1% vs. 0.4%; relative risk 3.0; 95% CI, 0.3–28.5), and recurrence of PE was rare in both groups (0.4% vs. 0.4%; relative risk 1.0; 95% CI, 0.1–15.8).
Safety outcomes showed no statistically significant increase in major bleeding. Within 7 days, major bleeding occurred in 4.1% of the USCDT group versus 2.2% in the control group (p=0.32), and at 30 days in 4.1% versus 3.0% (relative risk 1.4; 95% CI, 0.6–3.4; p=0.64). Importantly, no intracranial hemorrhage occurred in either group. Rates of death at 30 days (1.8% vs. 1.1%) and serious adverse events (14.8% vs. 16.2%; p=0.64) were similar between groups. Additional findings demonstrated lower use of rescue therapy in the intervention group (2.9% vs. 9.2%), consistent with improved early hemodynamic stability. Hospital length of stay and functional outcomes at 30 days were similar between groups, though there was a trend toward shorter hospitalization with USCDT.
Dr. Stavros V. Konstantinides, the study’s lead investigator, stated: “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. If the right patients are selected, it can prevent deterioration at an acceptably low risk of bleeding.”