HI-PEITHO
Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism
Presented by Stavros Konstantinides — Johannes Gutenberg University
Subspecialty: Pulmonary Embolism
Published in NEJM
Key Result
Ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduced the composite of PE-related death, cardiopulmonary decompensation, or symptomatic recurrence by 61% vs anticoagulation alone (4.0% vs 10.3%; RR 0.39, 95% CI 0.20-0.77, P=0.005) with no increase in major bleeding.
What did this trial find?
The HI-PEITHO trial (N=544) showed that ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation reduced the composite of PE-related death, cardiorespiratory decompensation, or symptomatic recurrence by 61% vs anticoagulation alone (4.0% vs 10.3%; P=0.005) in acute intermediate-risk PE, with no increase in major bleeding or intracranial hemorrhage. This is the first large RCT to demonstrate superiority of a catheter-based strategy over anticoagulation alone in this population. There is meaningful debate about generalizability given strict enrollment criteria (~87% screened out), the reliance on the NEWS score to define decompensation, and cautions against extrapolating to lower-risk intermediate PE patients.
Why does this trial matter?
Real controversy and meaningful interpretation debate. While the primary endpoint was clearly positive, there is substantial expert discussion about: (1) generalizability given ~87% of screened patients were excluded, (2) reliance on the NEWS score to define decompensation rather than traditional hard endpoints, (3) no mortality benefit or functional status difference at 30 days, (4) resource utilization concerns, and (5) cautions from guideline writers and editorialists against extrapolating to less severe intermediate-risk PE. This trial has rich, multi-perspective coverage with genuine disagreement about clinical significance.
Study Design
Multinational, adaptive-design, randomized controlled trial with blinded outcome adjudication
Clinical Implications
In patients with acute intermediate-risk PE who have signs of cardiorespiratory distress, catheter-directed fibrinolysis significantly reduces the risk of clinical deterioration without increasing major bleeding or intracranial hemorrhage. This may shift practice toward earlier intervention in this population.
Abstract
Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of >=1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of <=110 mm Hg, a heart rate of >=100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group). The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean age was 58.2+/-13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%) in the intervention group and 28 (10.3%) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P=0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P=0.32). No intracranial hemorrhage occurred.