This study aims to compare the effectiveness and safety of three treatment strategies (Anticoagulation, Thrombolysis, and Mechanical Thrombectomy) for patients with intermediate-high risk acute pulmonary embolism (PE) in a real-world setting. Approximately 1,300 patients will be enrolled across multiple centers in China. Patients will be followed for 90 days to assess mortality, heart function recovery, bleeding risks, and quality of life. The results will help guide personalized treatment decisions and healthcare policy.

Background: Acute pulmonary embolism (PE) is a severe manifestation of venous thromboembolism (VTE). Intermediate-high risk PE accounts for 20-30% of all PE cases with significant mortality driven by right ventricular (RV) dysfunction. Current guidelines recommend anticoagulation for all, with thrombolysis or mechanical thrombectomy as rescue or alternative therapies. However, there is significant heterogeneity in real-world treatment selection and a lack of head-to-head comparative evidence among the three strategies in complex real-world populations.

Objective: To compare the 30-day and 90-day all-cause mortality and 48-hour RV/LV ratio improvement rate among three treatment strategies (Anticoagulation, Thrombolysis, Mechanical Thrombectomy) in patients with intermediate-high risk acute PE.

Design: This is a prospective, multicenter, non-randomized, pragmatic cohort study. Treatment allocation is based on routine clinical decision-making (natural allocation) without investigator intervention. Advanced statistical methods (Propensity Score Matching/Weighting, Instrumental Variable analysis) will be used to control for confounding factors.

Participants: 1,300 patients with confirmed acute intermediate-high risk PE (RV/LV ratio ≥0.9 and elevated cardiac biomarkers, hemodynamically stable). There are no age limits to reflect real-world diversity.

Interventions/Exposures:

1. Anticoagulation (AC): Standard anticoagulant therapy (LMWH, DOAC, UFH, or Warfarin).
2. Thrombolysis (TL): Systemic thrombolysis or Catheter-Directed Thrombolysis (CDT) using agents like Urokinase, Alteplase, etc.
3. Mechanical Thrombectomy (MT): Mechanical removal of thrombus using FDA/NMPA approved devices (e.g., Indigo, FlowTriever, Acoscream), with or without adjunctive anticoagulation/thrombolysis.

Outcomes:

• Primary: 30-day and 90-day all-cause mortality; 48-hour RV/LV ratio improvement rate (≥15% reduction).
• Secondary: Clinical deterioration, major bleeding (ISTH/GUSTO/BARC), functional status (6MWT, NYHA, PVFS), quality of life (PEmb-QoL, EQ-5D-5L), PE recurrence, and healthcare resource utilization.

Follow-up: Patients will be followed at 48 hours, 7 days, 30 days, and 90 days.

Inclusion Criteria:

• Age unlimited (reflecting real-world population).
• Symptom duration of acute PE ≤ 14 days.
• Confirmed acute PE by CTPA involving main or lobar pulmonary arteries.
• Defined as Intermediate-High Risk PE meeting all of the following:
• RV/LV ratio ≥ 0.9 (by CT or Echocardiography).
• Elevated cardiac biomarkers (Troponin > 99th percentile or BNP > 100 pg/mL).
• Hemodynamically stable (SBP ≥ 90 mmHg, no vasopressors required).
• Able to provide informed consent and complete follow-up.

Exclusion Criteria:

• Already received thrombolysis or mechanical thrombectomy for the current episode prior to enrollment.
• Unable to obtain baseline or follow-up CTPA imaging.
• (Note: Unlike strict RCTs, patients with cancer, renal insufficiency, or advanced age are NOT excluded to ensure real-world representativeness).

Patients diagnosed with intermediate-high risk acute pulmonary embolism admitted to participating tertiary hospitals with Pulmonary Embolism Response Teams (PERT).

De-identified individual participant data (IPD) and data dictionaries will be made available to researchers upon reasonable request after the publication of the primary results.

Starting 6 months after publication of the primary results, available for 5 years.

Data will be shared with researchers who provide a methodologically sound proposal and whose use of data is for legitimate research purposes. Requests should be directed to the Principal Investigator.