HI-PEITHO Trial Reports Lower Early PE Events with Fibrinolysis

Key Takeaways

• The 7-day composite event rate was lower with catheter-directed fibrinolysis plus anticoagulation than with anticoagulation alone, with a relative risk of 0.39.
• The trial enrolled patients with intermediate-risk pulmonary embolism, right ventricular strain, elevated troponin, and at least two indicators of cardiorespiratory distress, then randomized them to the two prespecified strategies.
• Major bleeding was reported in both groups, no intracranial hemorrhage occurred, and other serious adverse events were not substantially different through 30 days.

In HI-PEITHO, ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation was associated with fewer 7-day composite events than anticoagulation alone in acute intermediate-risk pulmonary embolism. The composite primary outcome occurred in 4.0% of patients assigned to the intervention and 10.3% assigned to anticoagulation alone.

The randomized trial enrolled patients with acute pulmonary embolism who met the study's intermediate-risk criteria and had evidence of right ventricular strain. It compared an interventional strategy with anticoagulation alone and focused on early clinical events during the first 7 days after randomization. In this population, the 7-day outcome favored the intervention strategy.

HI-PEITHO was a multinational, adaptive-design randomized trial with blinded outcome adjudication. Eligible patients had intermediate-risk pulmonary embolism, elevated troponin, and a right ventricular end-diastolic diameter to left ventricular end-diastolic diameter ratio of at least 1.0. They also had at least two indicators of cardiorespiratory distress before randomization. The intention-to-treat population included 544 patients, with 273 assigned to intervention and 271 to control; mean age was 58.2 years, and 42.6% were women. The trial compared ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation against anticoagulation alone.

The primary endpoint combined pulmonary embolism-related death, cardiorespiratory decompensation or collapse, and symptomatic recurrence of pulmonary embolism within 7 days. Events occurred in 4.0% of the intervention group and 10.3% of the control group. The reported 95% confidence intervals were 2.3 to 7.1 and 7.2 to 14.5, with a relative risk of 0.39 and P = 0.005. Investigators said the between-group difference was driven primarily by less cardiorespiratory decompensation or collapse in the intervention group than by other components. Overall, the intervention plus anticoagulation was associated with a lower risk of the composite outcome than anticoagulation alone during the 7-day assessment.

Major bleeding within 7 days was reported in 4.1% of the intervention group and 2.2% of the control group, with P = 0.32. Within 30 days, major bleeding was reported in 4.1% and 3.0%, respectively, with P = 0.64. No intracranial hemorrhage occurred, and no substantial between-group differences in other serious adverse events were observed through 30 days. These safety findings included major bleeding in both groups but no intracranial hemorrhage and no substantial difference in other serious adverse events through 30 days after randomization.