1Universitätsklinikum Schleswig-Holstein Medizinische Klinik II / Kardiologie, Angiologie, Intensivmedizin Lübeck, Deutschland; 2Herzzentrum der Universität zu Köln Klinik III für Innere Medizin Köln, Deutschland; 3Herzzentrum der Universität zu Köln Klinik für Kardiologie, Angiologie, Pneumologie und Internistische Intensivmedizin Köln, Deutschland
Background: Catheter-directed therapy (CDT) has emerged as potential treatment option for patients with intermediate-high and high-risk pulmonary embolism (PE). The availability of an ever-increasing variety of catheter systems offers the possibility of removing thrombotic material quickly from the pulmonary arteries and their branches. aiming to restore pulmonary blood flow. The three CDT systems most frequently reported in the literature are the EKOS™, FlowTriever, and AngioJet™. However, to date there are no randomized head-to-head trials that directly compare the respective systems. Thus, this single-arm meta-analysis aims to evaluate and compare the safety and efficacy of ultrasound-assisted thrombolysis (USAT by EKOS™), mechanical and aspiration thrombectomy (FlowTriever), and rheolytic thrombectomy (AngioJet™) in the management of intermediate-high and high-risk PE.
Methods: Systematical search in MEDLINE and EMBASE yielded 34 observational retrospective studies and two randomized controlled trials evaluating the safety and efficacy of the EKOSTM USAT thrombolysis catheter, AngioJet™ rheolytic thrombectomy system or FlowTriever mechanical thrombectomy system and fulfilling the inclusion criteria for meta-analysis. The three efficacy endpoints were 30-day mortality, reduction in RV/LV ration, and reduction in sPAP. Major bleeding according to BARC 3a constitutes the safety endpoint.
Main Results: 4,653 patients were included, comprising 2,301 who underwent EKOSTM USAT, 304 who underwent AngioJet™ rheolytic thrombectomy, and 2,048 who underwent FlowTriever CDT. There were no significant differences between the groups considering median age, sex, pulmonary embolism severity indices (PESI), pre-procedural RV/LV ratio and pre-procedural sPAP. The 30-day mortality rate was significantly higher in the AngioJet™ group (9% [95% CI, 6-15%], p<0.01) than in the FlowTriever (4% [95% CI, 2-8%]) and EKOSTM (2% [95% CI, 1-4%]) groups (Figure A), whereby there was no significant difference between the latter two groups (p=0.11). Regarding hemodynamic efficacy parameters, the RV/LV ratio reduction was significantly higher for EKOSTM (0.41 [95% CI, 0.35-0.47], p<0.05) than with AngioJet™ (0.29 [95% CI, 0.13-0.45]) or FlowTriever treatment (0.29 [95% CI, 0.21-0.37], Figure B). Accordingly, EKOSTM treatment has led to a significant higher reduction of sPAP compared with FlowTriever (17.05 mmHg [95% CI, .11.65-22.45 mmHg] vs. 9.81 mmHg [95% CI, .7.89-11.73 mmHg], p=0.02, Figure C). Regarding sPAP, AngioJet™ displayed no significant differences compared with the other treatments. Furthermore, there were no significant differences considering major bleeding occurrence (5% [95% CI, 5-8%] for EKOSTM, 4% [95% CI, 1-12%] for AngioJet™, and 3% [95% CI, 1-7%] for FlowTriever (p=0.61, Figure D).
Conclusion: CDT is an effective and safe treatment strategy in patients with PE. However, AngioJet™ treatment is associated with a higher mortality rate than EKOSTM and FlowTriever CDT. AngioJet™ associated bradycardia, pulmonary vasospasm, and increased mortality could be attributed to the release of adenosine from disrupted platelets due to the rheolytic thrombectomy. While major bleeding events are equally rare, there is a greater reduction in the RV/LV ratio and the sPAP under EKOSTM treatment compared to the FlowTriever in terms of hemodynamic effectiveness parameters. Hence, future randomized trials should address a head-to-head comparison of the two systems.