What is the treatment for pulmonary embolism (PE) in the acute setting?

Acute Treatment of Pulmonary Embolism

Immediately initiate anticoagulation upon suspicion of PE while diagnostic workup proceeds, with treatment stratified by hemodynamic stability: high-risk PE requires systemic thrombolysis, intermediate-risk PE requires anticoagulation with consideration for rescue thrombolysis if deterioration occurs, and low-risk PE is managed with anticoagulation alone, preferably using direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH) over unfractionated heparin. 1, 2, 3

Risk Stratification (Perform First)

Risk stratification must be completed immediately to guide treatment intensity 1, 2:

• High-risk PE: Sustained hypotension (systolic BP <90 mmHg for ≥15 minutes), cardiogenic shock, cardiac arrest, or requiring vasopressors 1, 2, 3
• Intermediate-risk PE: Hemodynamically stable but with evidence of right ventricular dysfunction on imaging or elevated cardiac biomarkers (troponin, BNP) 1, 2, 3
• Low-risk PE: Hemodynamically stable without RV dysfunction or myocardial injury 1, 2

High-Risk PE (Hemodynamically Unstable)

Systemic thrombolysis is the first-line treatment and should be administered immediately without delay 1, 2:

• Alteplase dosing: 100 mg IV over 90 minutes for stable patients, or 50 mg IV bolus for cardiac arrest 1
• Anticoagulation: Initiate unfractionated heparin (UFH) intravenously with weight-adjusted bolus (typically 80 U/kg bolus, then 18 U/kg/hour infusion) 4, 2, 3
• Supportive care: Norepinephrine and/or dobutamine should be considered for hemodynamic support 2

If thrombolysis is contraindicated or fails, surgical pulmonary embolectomy is recommended (operative mortality 20-50%, but acceptable for moribund patients) 4, 1, 2. Catheter-directed therapy should be considered as an alternative 2.

Critical caveat: DOACs (apixaban, rivaroxaban) are NOT recommended for initial treatment of hemodynamically unstable PE—UFH is mandatory 5, 6.

Intermediate-Risk PE (Hemodynamically Stable with RV Dysfunction)

Initiate anticoagulation immediately; routine primary thrombolysis is NOT recommended 1, 2:

• First-line anticoagulation: LMWH or fondaparinux preferred over UFH 1, 2, 3
• Monitoring: Continuous cardiac monitoring and serial vital signs every 4 hours minimum 3
• Rescue thrombolysis: Administer if hemodynamic deterioration occurs despite anticoagulation 1, 2

Low-Risk PE (Hemodynamically Stable, No RV Dysfunction)

Initiate anticoagulation without delay; DOACs are preferred over vitamin K antagonists 1, 2:

Preferred Anticoagulation Options (in order):

1. Direct Oral Anticoagulants (DOACs) - First choice 1, 2:

   • Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily 2
   • Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 2
   • Advantages: No need for parenteral overlap, predictable pharmacokinetics 7

2. LMWH or fondaparinux followed by oral anticoagulation 1, 2, 3

3. Unfractionated heparin - Reserved for specific situations only 3

When to Use UFH Instead of LMWH/DOACs:

UFH is preferred in the following situations 3, 7:

• Severe renal impairment (CrCl <30 mL/min)
• Hemodynamic instability
• High bleeding risk requiring rapid reversibility
• Severe obesity or extremes of body weight 8
• Patients being considered for thrombolysis 3

UFH dosing: 5000-10,000 U IV bolus, then continuous infusion at 18 U/kg/hour, adjusted to maintain aPTT 1.5-2.3 times control (corresponding to heparin level 0.30-0.60 anti-Xa U/mL) 4, 8

Absolute Contraindications to DOACs

Do NOT use DOACs in the following patients 2, 3, 5, 6:

• Severe renal insufficiency (CrCl <30 mL/min for apixaban; <15 mL/min avoid rivaroxaban)
• Pregnancy and lactation
• Antiphospholipid syndrome (especially triple-positive)
• Prosthetic heart valves
• Patients requiring thrombolysis or pulmonary embolectomy acutely

Early Discharge Considerations

Carefully selected low-risk PE patients should be considered for early discharge and home treatment 1, 2, 3:

• Must meet low-risk criteria at 48-hour reassessment 3
• No serious comorbidities or signs of heart failure 8
• Adequate home support and follow-up 1

Duration of Anticoagulation (Initial Phase)

• Acute phase: Continue therapeutic anticoagulation for at least 5-10 days 2
• Maintenance phase: Continue for minimum 3 months in all patients 1, 2, 3
• Provoked PE (transient risk factor): Discontinue after 3 months 1, 2
• Unprovoked PE or recurrent VTE: Consider indefinite anticoagulation 1, 2

Special Situations

Inferior vena cava (IVC) filters should be considered only in specific circumstances 1, 2:

• Acute PE with absolute contraindications to anticoagulation
• Recurrent PE despite therapeutic anticoagulation
• Routine use is NOT recommended 1, 2

Common Pitfalls to Avoid

• Never delay anticoagulation while awaiting diagnostic confirmation in patients with intermediate or high clinical probability 4, 3
• Do not use DOACs in hemodynamically unstable patients—this is explicitly contraindicated 5, 6
• Do not routinely thrombolyze intermediate-risk PE; reserve for hemodynamic deterioration 1, 2
• Monitor for bleeding continuously, especially in first 24-48 hours 3
• Avoid neuraxial procedures within 24 hours of last DOAC dose; wait 5 hours after catheter removal before next dose 5