Comparative Efficacy and Safety of Reperfusion Strategies for Acute Intermediate-Risk Pulmonary Embolism: A Systematic Review and Network Meta-Analysis of Randomised Trials

Background: The optimal initial reperfusion strategy for acute intermediate-risk pulmonary embolism remains uncertain. We compared anticoagulation, systemic thrombolysis, catheter-directed thrombolysis, ultrasound-assisted catheter-directed thrombolysis, large-bore aspiration thrombectomy, and catheter-assisted aspiration thrombectomy in a risk-stratified network meta-analysis of randomised trials.<br><br>Methods: The protocol was registered with PROSPERO (CRD420261417361).We searched PubMed/MEDLINE, Embase, CENTRAL, Web of Science, CNKI, Wanfang, VIP, SinoMed, ClinicalTrials.gov, and WHO ICTRP from inception to May 11, 2026, without language restrictions. Eligible studies were randomised controlled trials in adults with acute intermediate-risk pulmonary embolism. NMA-2 was the primary intermediate-high-risk network; NMA-3 was an all-intermediate-risk validation network. Frequentist random-effects network meta-analysis estimated odds ratios (ORs) and 95% CIs for five core binary outcomes. Certainty was assessed with RoB 2.0 and CINeMA/GRADE.<br><br>Findings: Nineteen trials including 3548 participants were included. In NMA-2, systemic thrombolysis and ultrasound-assisted catheter-directed thrombolysis reduced clinical deterioration versus anticoagulation alone (systemic thrombolysis: OR 0.36, 95% CI 0.17-0.76; ultrasound-assisted catheter-directed thrombolysis: OR 0.33, 0.16-0.66) and treatment escalation or rescue reperfusion (systemic thrombolysis: OR 0.28, 0.09-0.85; ultrasound-assisted catheter-directed thrombolysis: OR 0.29, 0.10-0.82). No strategy showed a robust mortality reduction. Systemic thrombolysis increased major bleeding (OR 4.69, 2.63-8.34) and intracranial haemorrhage (OR 10.04, 1.28-78.73); ultrasound-assisted catheter-directed thrombolysis increased major bleeding (OR 2.83, 1.29-6.20). Large-bore aspiration thrombectomy ranked favourably for efficacy outcomes, but this signal was sparse, indirect versus anticoagulation, and PEERLESS-sensitive. Catheter-assisted aspiration thrombectomy ranked favourably for bleeding safety, but efficacy evidence was limited and uncertain. NMA-3 broadly supported the primary efficacy findings.<br><br>Interpretation: Systemic thrombolysis and ultrasound-assisted catheter-directed thrombolysis reduce early clinical deterioration and treatment escalation in intermediate-high-risk pulmonary embolism, but mortality benefit is unproven. Systemic thrombolysis has an important bleeding penalty. Among device-based strategies, large-bore aspiration thrombectomy showed favourable efficacy rankings but PEERLESS-sensitive evidence, whereas catheter-assisted aspiration thrombectomy showed favourable bleeding-safety rankings but less certain efficacy evidence. Current evidence supports selective, risk-adapted reperfusion rather than routine escalation for all intermediate-risk pulmonary embolism.