What are the current American College of Cardiology guidelines for risk‑stratified assessment and management of acute pulmonary embolism, including anticoagulation, thrombolysis, outpatient treatment, and therapy duration?

Latest ACC/ESC Pulmonary Embolism Guidelines: Risk-Stratified Management

Immediate Risk Stratification

The cornerstone of modern PE management is immediate hemodynamic assessment: patients with shock or persistent hypotension (systolic BP < 90 mmHg) constitute high-risk PE requiring urgent reperfusion therapy, while hemodynamically stable patients are further stratified by right ventricular dysfunction and cardiac biomarkers to guide anticoagulation strategy. 1

High-Risk (Massive) PE

• Shock, persistent hypotension, or cardiac arrest defines high-risk PE with 15–25% early mortality. 1, 2
• Initiate unfractionated heparin (UFH) immediately with weight-adjusted bolus even before imaging confirmation. 1
• Administer systemic thrombolysis without delay to all high-risk patients unless absolute bleeding contraindications exist; this significantly reduces mortality (OR 0.53, NNT 59). 1, 3
• Alteplase dosing: 100 mg over 2 hours, or 0.6 mg/kg over 15 minutes (maximum 50 mg) in extreme cases. 1
• If thrombolysis is contraindicated or fails within one hour, proceed to surgical pulmonary embolectomy. 1

Intermediate-Risk PE (Normotensive with RV Dysfunction)

• Hemodynamically stable patients with RV dysfunction on echo/CTPA and/or elevated troponin/BNP comprise intermediate-risk. 1, 2
• Subdivide into intermediate-high (both RV dysfunction AND biomarker elevation) versus intermediate-low (only one present). 1
• Do NOT use routine systemic thrombolysis in intermediate-risk PE; anticoagulation alone is standard. 1, 4
• Reserve thrombolysis for rescue therapy if hemodynamic deterioration occurs despite anticoagulation. 1

Low-Risk PE

• Hemodynamically stable without RV dysfunction or biomarker elevation. 1
• Candidates for early discharge and outpatient treatment using simplified PESI score or Hestia criteria combined with physician assessment. 1, 2

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Diagnostic Algorithm

Clinical Probability First

• Always apply a validated prediction rule (Wells or Geneva score) before any testing to stratify into low/intermediate/high probability. 1, 5
• In high clinical probability, proceed directly to CTPA—never measure D-dimer as a normal result does not exclude PE. 1, 5

D-dimer Strategy

• Measure D-dimer only in low or intermediate probability patients using highly sensitive assays. 1, 5
• A normal D-dimer excludes PE without further testing when clinical probability is low/intermediate (3-month VTE risk < 1%). 1, 5

Imaging

• CTPA is first-line imaging for stable patients with elevated D-dimer or high clinical probability. 1, 5
• Accept PE diagnosis when CTPA shows segmental or more proximal filling defect in intermediate/high probability patients. 1, 5
• V/Q scintigraphy is valid when CTPA is contraindicated; normal perfusion scan excludes PE. 1, 5
• Do NOT perform CT venography as adjunct to CTPA or use MRA to rule out PE. 1, 5
• In unstable patients when CT unavailable, bedside echocardiography showing RV overload justifies immediate treatment. 1, 5

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Anticoagulation Selection

Initial Parenteral Therapy

• UFH is mandatory for high-risk PE due to short half-life and reversibility with protamine. 1
• For intermediate- and low-risk PE, prefer LMWH or fondaparinux over UFH as they have lower bleeding risk and facilitate outpatient management. 1, 6
• Start anticoagulation immediately in high/intermediate clinical probability while diagnostic workup proceeds—never delay. 1

Oral Anticoagulation

• Direct oral anticoagulants (DOACs)—apixaban, rivaroxaban, edoxaban, or dabigatran—are preferred over warfarin for all eligible patients. 1, 6, 7
• Absolute DOAC contraindications: severe renal impairment (CrCl < 25–30 mL/min), antiphospholipid antibody syndrome, pregnancy/lactation. 1, 6, 7
• When warfarin is used, overlap with parenteral anticoagulation until INR 2.0–3.0 on two consecutive measurements ≥ 24 hours apart. 1

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Duration of Anticoagulation: Algorithmic Decision

Minimum 3 Months for All Patients

• Every PE patient requires at least 3 months of therapeutic anticoagulation, regardless of risk category. 1, 6, 7

Decision at 3–6 Month Reassessment

Provoked PE (major transient risk factor: surgery, trauma, immobilization):

• STOP anticoagulation at 3 months—recurrence risk is low. 1, 6

Unprovoked PE (no identifiable transient trigger):

• CONTINUE indefinitely if bleeding risk is low-to-moderate—annual recurrence exceeds 5% and outweighs bleeding risk. 1, 6
• Consider reduced-dose DOAC (apixaban 2.5 mg bid or rivaroxaban 10 mg daily) for extended therapy if bleeding risk is moderate. 1, 6

Recurrent VTE (≥ 1 prior unprovoked episode):

• CONTINUE indefinitely—recurrence risk is prohibitive. 1

Antiphospholipid antibody syndrome:

• CONTINUE warfarin indefinitely—DOACs are contraindicated. 1, 7

Active cancer:

• CONTINUE indefinitely; apixaban, edoxaban, or rivaroxaban are effective alternatives to LMWH. 6

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Follow-Up and CTEPH Screening

Mandatory 3–6 Month Reassessment

• All patients require clinical evaluation at 3–6 months to assess persistent dyspnea, functional limitation, bleeding events, and adherence. 1, 8
• If persistent dyspnea or functional limitation exists, perform V/Q scintigraphy to detect mismatched perfusion defects. 1, 8
• Refer to CTEPH expert center when V/Q shows persistent defects; chronic thromboembolic pulmonary hypertension develops in 2–4% of PE survivors. 8

Extended Anticoagulation Monitoring

• Patients on indefinite anticoagulation require yearly reassessment of bleeding risk, organ function, adherence, and drug tolerance. 1

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Critical Pitfalls to Avoid

• Never delay anticoagulation in high/intermediate probability PE while awaiting diagnostic confirmation—mortality risk exceeds bleeding risk. 1
• Never measure D-dimer in high clinical probability—proceed directly to CTPA. 1, 5
• Never use DOACs in severe renal impairment (< 25–30 mL/min) or antiphospholipid syndrome—warfarin is mandatory. 1, 7
• Never discontinue anticoagulation at 3 months in unprovoked PE without formal bleeding-risk assessment—annual recurrence exceeds 5%. 1, 6
• Never lose patients to follow-up—routine 3–6 month reassessment is essential for detecting CTEPH and guiding anticoagulation duration. 1, 8
• Never use routine IVC filters—reserve only for absolute anticoagulation contraindications. 1
• Never ignore persistent dyspnea—it may indicate CTEPH requiring specialized evaluation and lifelong anticoagulation. 8