BACKGROUND: Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain.
METHODS: 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) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days.
RESULTS: The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) 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%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) 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); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred.
CONCLUSIONS: In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Hospital Doctor/Hospitalists |  |
| Internal Medicine | |
| Hemostasis and Thrombosis | |
The decision to pursue catheter-directed fibrinolysis of acute pulmonary embolism (either moderate or severe) is generally not isolated to the emergency department. For severe PE, many hospitals have developed PE Response Teams (PERT) and the decision is shared between Interventional Radiology (IR), Cardiology, and Critical Care Medicine. The moderate risk PEs of HI-PEITHO are likely less urgent than the severe PE subset and would more likely be a decision between IR, Cardiology, and the inpatient team.
This is a well-done trial of patients with intermediate-risk pulmonary embolism (PE) (with a ratio of right to left ventricular end-diastolic diameter =1.0 and elevated troponin) and =2 of cardio-respiratory distress indicators (systolic blood pressure =110, pulse =100, or respiratory rate >20) who were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (intervention group) or anticoagulation alone (control group). There was no difference in PE-related mortality or recurrence, but there was benefit in prevention of cardiorespiratory decompensation or collapse (defined as =1 of: cardiac arrest, indication for cardiopulmonary resuscitation, signs of shock, extracorporeal membrane oxygenation, intubation, noninvasive mechanical ventilation, or National Early Warning Score = 9). The number needed to treat was 15 (95% confidence interval 9, 41). There were no significant differences in major bleeding events.
Disappointing that there was no overall survival benefit.
Improved composite outcome with catheter-directed thrombolysis, although due to decreased decompensation with no impact on mortality.
well designed trial of ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation for patients with intermediate-risk pulmonary embolism. Prospective RCT of 544 patients. Criteria for eligibility well defined. They wanted to minimize risks of thrombolysis by using catheter-directed fibrinolysis along with high-frequency, low-power ultrasound energy to potentiate fibrinolytic effects. They were able to reduce the risk of deterioration with a non-significant increase in bleeding complications in the intervention group. Most of the benefit was seen in preventing cardiorespiratory decompensation or collapse (10/273 vs 28/271). Further study needed to confirm the findings. I expect to see future interventional adjuncts to thrombolytic therapy to reduce risks.
Ultrasound-facilitated catheter-directed thrombolysis in intermediate risk pulmonary embolism (PE) added to anticoagulation shows benefit in this patient population in terms of low PE-related complications.
I wonder about the choice of control. I would be interested in seeing systemic fibrinolytics included.