Efficacy and safety of low-dose thrombolysis in intermediate-risk pulmonary embolism: a meta-analysis

Objective To systematically evaluate the efficacy and safety of low-dose thrombolysis in patients with intermediate-risk pulmonary embolism (PE). Methods A systematic search was conducted in PubMed, Embase, and the Cochrane Library up to December 6, 2025. Randomized controlled trials (RCTs), non-randomized controlled studies, and cohort studies investigating low-dose thrombolysis for intermediate-risk PE were included. Two researchers independently screened the literature, extracted data, and assessed study quality. A meta-analysis was performed using Stata software (version 16.0) to calculate pooled estimates of mortality, bleeding incidence, and recurrence rates. The efficacy and safety of low-dose thrombolysis were compared with those of anticoagulation alone or full-dose thrombolysis. Results This meta-analysis included 13 studies (1,018 patients with intermediate-risk PE). Low-dose thrombolysis yielded a 1-month and 1-year mortality of 2% (95% CI: 0.00–0.03; 0.00–0.05), recurrence of 1% (95% CI: 0.00–0.02), major bleeding of 1% (95% CI: 0.00–0.03), and minor bleeding of 7% (95% CI: 0.05–0.10). Subgroup analysis showed ultrasound-assisted catheter-directed thrombolysis (USAT) had 1-month and 1-year mortality rates of 2% (95% CI: 0.01–0.04) and 1% (95% CI: 0.00–0.03), respectively, vs. 1% (95% CI: 0.00–0.03) and 7% (95% CI: 0.01–0.16) for low-dose systemic thrombolysis. Compared to anticoagulation alone or full-dose thrombolysis, low-dose systemic thrombolysis showed no significant differences in mortality or recurrence, but had lower bleeding risk than full-dose thrombolysis (RD = −0.23, 95% CI: −0.44 to −0.01). USAT significantly reduced 1-month mortality vs. anticoagulation alone (RD = −0.09, 95% CI: −0.13 to −0.04); however, this stems from a single non-randomized study requiring RCT validation. Bleeding rates showed no significant difference. Conclusion In patients with intermediate-risk PE, low-dose thrombolysis yields low mortality and recurrence rates with an acceptable bleeding risk. Compared with full-dose thrombolysis, it offers a safety advantage by reducing the incidence of bleeding; however, its comparative efficacy regarding mortality and recurrence remains undetermined and may be equivalent. Further high-quality RCTs are warranted. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261284475 .