B67-19 Real-world Comparative Effectiveness of Systemic Thrombolysis Versus Ultrasound-assisted Catheter-directed Thrombolysis, With and Without Escalation Strategy, in Massive Pulmonary Embolism

Rationale Massive pulmonary embolism (PE) remains a life-threatening emergency with persistently high short-term mortality despite advances in reperfusion therapy. Systemic thrombolysis is the current first-line treatment but is limited by major bleeding and incomplete hemodynamic recovery. Ultrasound-assisted catheter-directed thrombolysis (EKOS) allows targeted fibrinolysis with lower systemic thrombolytic exposure and potentially improved safety. However, comparative real-world data assessing outcomes between systemic thrombolysis, EKOS alone, and escalation strategies combining both approaches remain limited—particularly with respect to longer-term mortality. Methods We performed a multicenter retrospective cohort analysis using the TriNetX Research Network, a global database of de-identified electronic health records. Adults hospitalized with massive PE were identified using ICD-10-CM code I26.0x (PE with acute cor pulmonale). Systemic thrombolysis was identified through procedural and medication codes for alteplase (J2997), tenecteplase (J3101), or urokinase (J3360). EKOS therapy was captured via catheter-directed thrombolysis procedure codes (CPT 37211-37214) without concurrent systemic infusion, whereas escalation therapy was defined as both interventions performed within 24-48 hours. The primary outcome was 90-day all-cause mortality; secondary outcomes included ICU admission and right-sided heart failure. Propensity-score matching (1:1, caliper 0.2 SD) adjusted for demographics and comorbidities including CVA, liver disease, heart failure, chronic kidney disease, COPD, and malignancy. Results Two propensity-matched comparisons were conducted: (1) systemic thrombolysis versus EKOS alone (143 patients per group), and (2) systemic thrombolysis escalated to EKOS versus systemic thrombolysis alone (633 patients per group). At 90 days, mortality was 12.6% in the EKOS group versus 20.1% with systemic thrombolysis (p = 0.08), and 10.9% versus 22.4% for escalation therapy compared with systemic thrombolysis alone (p < 0.001). ICU admission occurred in 19.6% of EKOS versus 27.3% of systemic thrombolysis patients, and 2.5% versus 3.5% in the escalation cohort. Right-sided heart failure was observed in 5.1% of patients in both escalation and thrombolysis-only groups (p = 1.0). Overall, EKOS-based strategies were consistently associated with lower 90-day mortality and reduced ICU utilization, with mortality benefit reaching statistical significance in the escalation cohort. Conclusion In this large real-world study, EKOS-based reperfusion strategies were linked to lower 90-day mortality and reduced ICU utilization compared with systemic thrombolysis alone in patients with massive PE. The survival benefit was statistically significant when EKOS was employed as an escalation therapy, while rates of right-sided heart failure remained similar. These findings highlight the potential value of integrating catheter-directed reperfusion within escalation pathways for high-risk PE and underscore the need for prospective validation in future trials.