Management of high-risk acute pulmonary embolism: an emulated target trial analysis
Authors: Andrea Stadlbauer, Tom Verbelen, Leonhard Binzenhöfer, Tomaz Goslar, Alexander Supady, Peter M. Spieth, Marko Noc, Andreas Verstraete, Sabine Hoffmann, Michael Schomaker, Julia Höpler, Marie Kraft, Esther Tautz, Daniel Hoyer, Jörn Tongers, Franz Haertel, Aschraf El-Essawi, Mostafa Salem, Rafael Henrique Rangel, Carsten Hullermann, Marvin Kriz, Benedikt Schrage, Jorge Moisés, Manel Sabate, Federico Pappalardo, Lisa Crusius, Norman Mangner, Christoph Adler, Tobias Tichelbäcker, Carsten Skurk, Christian Jung, Sebastian Kufner, Tobias Graf, Clemens Scherer, Laura Villegas Sierra, Hannah Billig, Nicolas Majunke, Walter S. Speidl, Robert Zilberszac, Luis Chiscano-Camón, Aitor Uribarri, Jordi Riera, Roberto Roncon-Albuquerque, Elizabete Terauda, Andrejs Erglis, Guido Tavazzi, Uwe Zeymer, Maike Knorr, Juliane Kilo, Sven Möbius-Winkler, Robert H. G. Schwinger, Derk Frank, Oliver Borst, Helene Häberle, Frederic De Roeck, Christiaan Vrints, Christof Schmid, Georg Nickenig, Christian Hagl, Steffen Massberg, Andreas Schäfer, Dirk Westermann, Sebastian Zimmer, Alain Combes, Daniele Camboni, Holger Thiele, Enzo Lüsebrink, Tom Adriaenssens, Hugo Lanz, Nils Gade, Daniel Roden, Inas Saleh, Kirsten Krüger, Jochen Dutzmann, Jan Sackarnd, Benedikt Beer, Jeisson Osorio, Karsten Hug, Ingo Eitel, Evija Camane, Santa Strazdina, Līga Vīduša, Silvia Klinger, Antonia Wechsler, Sven Peterss, Nikolaus Kneidinger, Andrea Montisci, Karl Toischer
Journal: Intensive Care Medicine (2025)

High-risk acute pulmonary embolism (PE) is a life-threatening condition necessitating hemodynamic stabilization and rapid restoration of pulmonary perfusion. In this context, evidence regarding the benefit of advanced circulatory support and pulmonary recanalization strategies is still limited. In this observational study, we assessed data of 1060 patients treated for high-risk acute PE with 991 being included in a target trial emulation to investigate all-cause in-hospital mortality estimates with different advanced treatment strategies. The four treatment groups consisted of patients undergoing (I) veno-arterial extracorporeal membrane oxygenation (VA-ECMO) alone (n = 126), (II) intrahospital systemic thrombolysis (SYS) (n = 643), (III) surgical thrombectomy (ST) (n = 49), and (IV) percutaneous catheter-directed treatment (PCDT) (n = 173). VA-ECMO was allowed as bridging to pulmonary recanalization in groups II, III, and IV. Marginal causal contrasts were estimated using the g-formula with logistic regression models as the primary approach. Sensitivity analyses included targeted maximum likelihood estimation (TMLE) with machine learning, inverse probability of treatment weighting (IPTW), as well as variations of estimands, handling of missing values, and a complete target trial emulation excluding the VA-ECMO alone group. In the overall target trial population, the median age was 62.0 years, and 53.3% of patients were male. The estimated probability of in-hospital mortality from the primary target trial intention-to-treat analysis for VA-ECMO alone was 57% (95% confidence interval [CI] 47%; 67%), compared to 48% (95% CI 44%; 53%) for intrahospital SYS, 34% (95%CI 18%; 50%) for ST, and 43% (95% CI 35%; 51%) for PCDT. The mortality risk ratios were largely in favor of any advanced recanalization strategy over VA-ECMO alone. The robustness of these findings was supported by all sensitivity analyses. In the crude outcome analysis, patients surviving to discharge had a high probability of favorable neurologic outcome in all treatment groups. Advanced recanalization by means of SYS, ST, and several promising catheter-directed systems may have a positive impact on short-term survival of patients presenting with high-risk PE compared to the use of VA-ECMO alone as a bridge to recovery.