Ultrasound facilitated catheter directed thrombolysis versus anticoagulation alone for intermediate risk pulmonary embolism: a systematic review and meta-analysis with trial sequential analysis

Ultrasound-facilitated catheter directed thrombolysis (USAT) is increasingly used for intermediate risk pulmonary embolism, but prior syntheses pooled ultrasound facilitated and conventional catheter devices together, precluding device specific conclusions, and none tested pooled estimates against trial sequential analysis (TSA). This is the first meta-analysis restricted exclusively to USAT, incorporating the newly published HI-PEITHO trial and applying both TSA and prespecified subgroup analysis by design and follow-up duration. Four databases were searched from inception through July 2026 per PRISMA 2020. Six studies, two randomized trials and four observational comparisons totaling 1,646 patients, comparing USAT with anticoagulation alone in intermediate or intermediate high risk pulmonary embolism were included. Dichotomous outcomes were pooled as risk ratios (RR) and continuous outcomes as mean differences using random effects models, with risk of bias assessed via RoB 2 and Newcastle Ottawa Scale and certainty via GRADE. USAT was associated with a non-significant reduction in overall all-cause mortality (RR 0.60, 95% CI 0.36 to 1.02; p = 0.06), and with lower mortality at one year (RR 0.40, 95% CI 0.19 to 0.84; p = 0.02; Very Low certainty), but not at thirty days (RR 0.76, 95% CI 0.14 to 4.14; p = 0.75). This benefit was significant in observational studies (RR 0.50, 95% CI 0.29 to 0.86; p = 0.01) but not in randomized trials (RR 1.43, 95% CI 0.36 to 5.65; p = 0.61), and leave-one-out analysis showed the overall mortality estimate remained non-significant on removal of any single study except Rosenfield 2026/HI-PEITHO, whose removal alone restored significance (RR 0.50, 95% CI 0.29 to 0.85; p = 0.01). Major bleeding (RR 1.96, 95% CI 0.62 to 6.23) and minor bleeding (RR 2.26, 95% CI 0.80 to 6.36) trended higher with USAT without reaching significance. Recurrent pulmonary embolism and length of hospital stay showed no significant difference between arms, and right ventricular dysfunction improvement was numerically higher with USAT (RR 1.29, 95% CI 0.48 to 3.44) without reaching significance. Pulmonary artery pressure showed no significant difference (MD − 1.37 mmHg, 95% CI − 4.97 to 2.24) when analyzed using follow up absolute measurements from the two eligible observational studies, excluding one randomized trial that reported a non-comparable 24 h change from baseline value. No outcome, including mortality, reached its Required Information Size on TSA. This first device specific synthesis, incorporating trial sequential analysis, found no significant overall mortality benefit of USAT when HI-PEITHO’s mortality outcome is analyzed on an intention-to-treat basis; a significant reduction was observed only in observational comparisons and at one year. Routine use over anticoagulation cannot be recommended pending adequately powered trials.