Reperfusion treatment strategies in acute pulmonary embolism: Study protocol for a multicenter prospective observational study in the Nordic countries (PE-NORDIC)

<h2>Abstract</h2><h3>Background</h3> Guidelines recommend systemic thrombolysis (ST) as first-line reperfusion therapy for highrisk pulmonary embolism (PE), however, clinical concerns regarding bleeding risk frequently limit its use in clinical practice. Catheter-directed therapy (CDT) should be considered when ST is contraindicated or has failed but is increasingly used outside these recommendations despite limited guideline support. Prospective data on short- and long-term outcomes after CDT, particularly in relation to a concurrent ST–treated population, remain scarce. PE-NORDIC aims to evaluate short- and long-term outcomes after CDT and ST for PE in the Nordic countries. <h3>Methods</h3> In this multicenter prospective observational study conducted in the Nordics, 244 adult patients with confirmed acute PE treated with CDT or ST will be enrolled and followed for up to 1 year. The primary outcome is a composite of all-cause mortality or severe bleeding within 30 days. Secondary outcomes include the individual components of the primary composite, need for rescue treatment, recurrent PE, length of stay in intensive care unit and hospital, right ventricular function, functional capacity, dyspnea, health-related quality of life, health economics, and PE complications. Analyses will be performed using multivariable regression models adjusted for relevant clinical confounders, with complementary propensity score-based methods. <h3>Strengths and limitations of this study</h3> <ul><li>•Multicenter prospective real-world study with comprehensive short- and long-term data collection in a rare patient population.</li><li>•Broad inclusion criteria enhancing generalizability.</li><li>•Pragmatic inclusion reflecting routine clinical practice, combined with structured and active follow-up.</li><li>•Non-randomized design with risk of confounding by indication and residual confounding, despite statistical adjustment.</li></ul>