Associate Professor of Radiology, Surgery, and Medicine Northwestern University Feinberg School of Medicine Chicago, Illinois, United States
Objective: Pulmonary embolism (PE) is a common and potentially life-threatening condition that often requires prompt and aggressive treatment. Anticoagulation, systemic thrombolysis, catheter-directed thrombolysis (CDT), ultrasound-accelerated thrombolysis (USAT), mechanical thrombectomy (mechanical, aspiration, or rheolytic) and surgical thrombectomy are all techniques associated with a published range of clinical outcomes. The aim of this analysis was to compare the in-hospital mortality rate of USAT to other treatments in PE patients.
Methods: A systematic literature review was conducted to identify randomized and non-randomized trials of the six treatment modalities prior to October 2021. A hierarchical random-effects model-based meta-analysis (MBMA) was applied to assess in-hospital mortality, the primary outcome, by incorporating the heterogeneity at three levels: treatment arm, clinical trial, and study design. A linear dose-response relationship was conducted to evaluate dose-effect modification. Patient risk was not included in the MBMA as a covariate due to lack of detailed reporting; however, a subpopulation analysis was performed within low, intermediate and high risk groups to assess the impact of risk stratification on the treatment effect.
Results: A total of 502 out of 2,173 retrieved abstracts were included for full-text review. Of these, one randomized controlled trial and 50 non-randomized (observational, prospective, retrospective) studies were pooled together in the MBMA. Among the included treatment options, USAT resulted in the lowest in-hospital mortality, significantly superior to standard CDT (HR=0.55 [0.46, 0.65]), surgical thrombectomy (HR=0.20 [0.16, 0.24]), and other mechanical thrombectomies (HR=0.44 [0.35, 0.56]). The lytic agent dose administered by USAT did not significantly impact mortality (p-value=0.775).A low dose of 8mg of rt-Pa resulted in a significant reduction of in-hospital mortality for USAT: vs. standard CDT (HR=0.67 [0.54, 0.84]); vs. surgical thrombectomy (HR=0.24 [0.19, 0.30]); vs. other thrombectomies (HR=0.55 [0.42, 0.72]). Retrospective studies had a much higher between-study variability in mortality data captured (standard deviation = 0.21 vs. 0.00 for other study types). Results of subpopulation analyses stratified by risk demonstrated that of the six treatment modalities, USAT provided the greatest impact in low risk PE patients (surface under the cumulative ranking curve (SUCRA) = 100%) and similar impact in intermediate & high risk PE patients, with CDT being non-significantly more effective (SUCRA = 89% for CDT and 84% for USAT, with HR=1.14 [0.83, 1.49] for USAT vs. CDT).
Conclusions: This meta-analysis demonstrated that USAT significantly reduced the risk of in-hospital mortality, regardless of lytic dose, with demonstrated safety and efficacy in general use outside the RCT setting. This study provides a systematic analysis of the available evidence on PE treatments to facilitate clinical treatment decision-making.