Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism.

BACKGROUND: Whether catheter-directed thrombolysis improves clinical outcomes in patients with intermediate-high-risk pulmonary embolism, as compared with anticoagulation alone, is uncertain. METHODS: In this multicenter, open-label, randomized trial, we randomly assigned patients with intermediate-high-risk acute pulmonary embolism (defined by hemodynamic stability, a simplified Pulmonary Embolism Severity Index score of ≥1, and right ventricular dysfunction plus an elevated level of cardiac troponin or natriuretic peptide) in a 1:1 ratio to receive catheter-directed thrombolysis with alteplase plus anticoagulation therapy (thrombolysis group) or anticoagulation therapy alone (standard-care group). The primary outcome was a composite of death from any cause, recurrence of pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization. Secondary outcomes included clinically relevant bleeding as defined by the Bleeding Academic Research Consortium, major bleeding as defined in the Global Use of Strategies to Open Occluded Coronary Arteries guidelines, and intracranial hemorrhage. RESULTS: A total of 558 patients underwent randomization; 280 were assigned to the thrombolysis group, and 278 to the standard-care group. The median age was 64 years, and 40.9% were female. A primary-outcome event occurred in 2 patients (0.7%) in the thrombolysis group and in 19 patients (6.8%) in the standard-care group (relative risk, 0.10; 95% confidence interval, 0.02 to 0.44; P<0.001); this difference was driven mainly by the lower incidence of cardiorespiratory decompensation or collapse in the thrombolysis group. By day 7, clinically relevant bleeding had occurred in 13 patients (4.6%) in the thrombolysis group and in 14 patients (5.0%) in the standard-care group (P = 0.85); major bleeding in 4 (1.4%) and 6 (2.2%), respectively (P = 0.54); and intracranial hemorrhage in 2 (0.7%) and none. One patient in the thrombolysis group died within 30 days, and 4 patients in the standard-care group died within 7 days. CONCLUSIONS: Among patients with intermediate-high-risk acute pulmonary embolism, catheter-directed thrombolysis with alteplase plus anticoagulation therapy led to a lower risk of death from any cause, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days after randomization than anticoagulation therapy alone. (Funded by the Ministry of Health of the Czech Republic and others; PRAGUE-26 ClinicalTrials.gov number, NCT05493163; EudraCT number, 2022-002218-18; European Union Clinical Trials number, 2024-516144-25-00.).