What is the latest guideline for diagnosing, risk‑stratifying, and treating pulmonary embolism, including anticoagulation choice, thrombolysis indications, and duration of therapy?

New Guidelines for Pulmonary Embolism

The 2026 European Society of Cardiology guidelines recommend immediate risk stratification based on hemodynamic stability, followed by direct oral anticoagulants (NOACs) as first-line therapy for eligible patients, with systemic thrombolysis reserved exclusively for high-risk PE presenting with shock or persistent hypotension. 1

Diagnosis

Clinical Probability Assessment

• Use validated prediction rules (Wells or Geneva score) to stratify patients into low, intermediate, or high clinical probability before ordering any diagnostic tests. 1
• Immediately assess for hemodynamic instability—defined as shock or systolic blood pressure < 90 mmHg for ≥15 minutes—to identify high-risk PE requiring urgent reperfusion therapy. 1, 2
• Both three-level (low/intermediate/high) and two-level (PE unlikely/PE likely) schemes are acceptable for clinical probability assessment. 1

D-dimer Testing

• Measure D-dimer only in patients with low or intermediate clinical probability using highly sensitive assays. 1
• Never measure D-dimer in patients with high clinical probability; proceed directly to imaging regardless of the result. 1, 3
• For patients over 50 years old, use age-adjusted D-dimer cutoffs (age × 10 ng/mL) to maintain >97% sensitivity while significantly increasing specificity. 2
• A normal D-dimer in low- or intermediate-probability patients safely excludes PE without further testing. 1

Imaging Strategy

• Computed tomography pulmonary angiography (CTPA) is the first-choice imaging test for hemodynamically stable patients with elevated D-dimer or high clinical probability. 1
• Accept a PE diagnosis when CTPA shows a segmental or more proximal filling defect in patients with intermediate or high clinical probability. 1
• Reject a PE diagnosis when CTPA is normal in patients with low or intermediate clinical probability. 1
• Ventilation-perfusion (V/Q) scintigraphy is a valid alternative when CTPA is contraindicated (e.g., severe renal impairment, contrast allergy); a normal perfusion scan excludes PE. 1, 2
• Do not perform CT venography as an adjunct to CTPA. 1
• Do not use magnetic resonance angiography (MRA) to rule out PE. 1
• Compression ultrasound demonstrating proximal deep-vein thrombosis in a patient with suspected PE confirms venous thromboembolism and justifies anticoagulation. 1

High-Risk PE Diagnostic Approach

• In suspected high-risk PE, perform bedside echocardiography or emergency CTPA depending on local availability. 1, 2
• Echocardiographic findings of right ventricular dysfunction (RV dilation, hypokinesis, or McConnell's sign) support the diagnosis in unstable patients. 1

Risk Stratification

Three-Tier Risk Classification

High-Risk (Massive) PE:

• Defined by shock, persistent systolic blood pressure < 90 mmHg, cardiac arrest, or pulselessness. 1, 2
• These patients have 15–25% early mortality and require immediate reperfusion therapy. 1

Intermediate-Risk PE:

• Hemodynamically stable patients with right ventricular dysfunction (on echocardiography or CTPA) and/or elevated cardiac biomarkers (troponin, BNP/NT-proBNP). 1, 4
• Subdivided into intermediate-high risk (both RV dysfunction and biomarker elevation) and intermediate-low risk (only one present). 1

Low-Risk PE:

• Hemodynamically stable without RV dysfunction or biomarker elevation. 1
• These patients are candidates for early discharge and outpatient treatment using tools like the Hestia criteria or simplified PESI score. 2

Treatment

High-Risk (Hemodynamically Unstable) PE

• Initiate intravenous unfractionated heparin (UFH) immediately with a weight-adjusted bolus (80 IU/kg or 5,000–10,000 units) followed by continuous infusion (18 IU/kg/h or 1,300 IU/h), even before imaging confirmation. 1, 3
• Target activated partial thromboplastin time (aPTT) of 1.5–2.5 times control (approximately 45–75 seconds), measured 4–6 hours after the bolus and then daily once therapeutic. 1, 3
• Administer systemic thrombolytic therapy immediately to all high-risk patients without a high bleeding-risk profile. 1, 2
• Alteplase dosing: 100 mg infused over 2 hours, or 0.6 mg/kg over 15 minutes (maximum 50 mg) in extreme cases. 1, 2
• Meta-analyses demonstrate a significant reduction in mortality or recurrence with thrombolysis in massive PE (OR 0.45; 95% CI 0.22–0.92), though major bleeding risk increases to 21.9% versus 11.9% with heparin alone. 1
• Surgical pulmonary embolectomy is indicated when thrombolysis is contraindicated or fails to improve hemodynamics within one hour. 1, 2
• Administer rescue thrombolytic therapy if hemodynamic deterioration occurs despite anticoagulation. 1, 3
• Catheter-directed embolectomy or thrombus fragmentation may be considered when surgery is unavailable, though evidence is limited. 1

Intermediate- and Low-Risk (Hemodynamically Stable) PE

• Start anticoagulation immediately in patients with high or intermediate clinical probability while diagnostic work-up proceeds. 1, 3
• For parenteral anticoagulation in stable patients, prefer low-molecular-weight heparin (LMWH) or fondaparinux over UFH. 1, 2
• Do not use systemic thrombolysis as routine primary treatment in intermediate- or low-risk PE. 1, 3
• Standard anticoagulation with close monitoring for deterioration is recommended for intermediate-high risk patients. 2

Oral Anticoagulation Choice

First-Line Therapy:

• Prefer a non-vitamin-K oral anticoagulant (NOAC)—apixaban, dabigatran, edoxaban, or rivaroxaban—over a vitamin K antagonist (VKA) for initiating oral therapy. 1, 3

Rivaroxaban Regimen (Single-Drug Approach):

• 15 mg orally twice daily for the first 21 days, then 20 mg once daily thereafter. 3
• No initial parenteral anticoagulation required. 3
• EINSTEIN-PE trial demonstrated non-inferiority to enoxaparin/warfarin for preventing recurrent VTE (2.1% vs 1.8%) with significantly lower major bleeding (1.1% vs 2.2%; P = 0.003). 3
• Hospital length of stay is shorter: 45% of patients discharged ≤5 days versus 33% with conventional therapy (P < 0.001). 3

Apixaban Regimen (Single-Drug Approach):

• 10 mg orally twice daily for the first 7 days, then 5 mg twice daily thereafter. 3
• No initial parenteral anticoagulation required. 3

Dabigatran or Edoxaban:

• Require therapeutic LMWH for at least 5 days before switching to the oral agent. 3

Vitamin K Antagonist (Warfarin):

• If a VKA is chosen, overlap with parenteral anticoagulation until the INR reaches 2.0–3.0 on two consecutive measurements taken at least 24 hours apart. 1, 3
• Starting dose: 10 mg daily in younger adults (< 60 years) and ≤5 mg daily in older adults. 3
• No INR monitoring is required for NOACs. 3

Absolute Contraindications to NOACs

• Severe renal impairment (creatinine clearance < 25–30 mL/min). 1, 3
• Antiphospholipid antibody syndrome (especially triple-positive disease). 1, 3
• Pregnancy or lactation. 1, 3
• Concurrent use of strong P-glycoprotein and CYP3A4 inhibitors (e.g., ritonavir, ketoconazole). 3
• In these cases, use a VKA indefinitely. 1, 3

Duration of Anticoagulation

Minimum Duration

• All patients with PE require therapeutic anticoagulation for a minimum of 3 months. 1, 3, 5

Provoked PE

• Discontinue anticoagulation after 3 months if the PE was provoked by a major transient/reversible risk factor (e.g., surgery, trauma, immobilization, pregnancy). 1, 3

Unprovoked PE

• Consider extended anticoagulation beyond 3 months if bleeding risk is low or moderate; the annual recurrence risk exceeds 5% and outweighs bleeding risk. 1, 3, 5
• After 6 months of full-dose therapy, a dose reduction to apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily can be considered to lower bleeding risk while preserving efficacy. 3
• Reassess regularly for tolerance, adherence, organ function, and bleeding risk at 3–6 months and then yearly. 1, 3

Recurrent VTE

• Continue oral anticoagulation indefinitely in patients with ≥1 prior episode of PE or DVT not linked to a transient risk factor. 1, 3

Special Populations

Antiphospholipid Antibody Syndrome:

• Continue VKA indefinitely; NOACs are contraindicated. 1, 3

Pregnancy:

• Use therapeutic fixed-dose LMWH based on early-pregnancy weight throughout gestation and for at least 6 weeks postpartum or 3 months from the index PE, whichever is longer. 1, 3
• NOACs and warfarin are contraindicated during pregnancy. 1, 3
• Warfarin may be initiated postpartum and does not preclude breastfeeding. 3

Active Cancer:

• Extended monotherapy with therapeutic LMWH (minimum 6 months and continued as long as cancer is active) is preferred over warfarin or NOACs. 3
• Patients with active malignancy have a three-fold higher risk of recurrent VTE. 3

Inferior Vena Cava (IVC) Filter Placement

• Do not routinely place IVC filters. 1, 3
• IVC filters are reserved only for patients with absolute contraindications to anticoagulation or who experience recurrent PE despite adequate anticoagulation. 1

Follow-Up and CTEPH Screening

• Routinely re-evaluate all patients 3–6 months after acute PE to assess for persistent dyspnea, functional limitation, signs of chronic thromboembolic pulmonary hypertension (CTEPH), medication adherence, drug tolerance, and any bleeding events. 1, 3
• Schedule regular follow-up visits at yearly intervals for patients on extended anticoagulation. 1
• If persistent or new-onset dyspnea or functional limitation is present, perform ventilation-perfusion (V/Q) scintigraphy to detect mismatched perfusion defects. 1, 3
• Refer symptomatic patients with mismatched perfusion defects on V/Q scan beyond 3 months to a pulmonary hypertension/CTEPH expert center, considering echocardiography, natriuretic peptide, and/or cardiopulmonary exercise testing results. 1, 3

Critical Pitfalls to Avoid

• Never delay anticoagulation in high- or intermediate-probability cases while awaiting diagnostic confirmation. 1, 3
• Never measure D-dimer in patients with high clinical probability; proceed directly to imaging. 1, 3
• Never use NOACs in patients with severe renal impairment (< 25–30 mL/min) or antiphospholipid syndrome; a VKA is mandatory. 1, 3
• Never discontinue anticoagulation at 3 months in unprovoked PE without weighing bleeding risk; the annual recurrence exceeds 5%. 1
• Never lose patients to follow-up after acute PE; routine reassessment at 3–6 months is essential for detecting CTEPH and guiding anticoagulation duration. 1
• Never withhold thrombolysis in massive PE solely because of relative contraindications; the mortality risk from untreated PE exceeds bleeding risk in life-threatening situations. 1
• Never use INR to monitor rivaroxaban or other NOAC activity, as INR does not correlate reliably with drug levels. 3