What is the recommended treatment for pulmonary embolism?

Treatment of Pulmonary Embolism

For most patients with confirmed pulmonary embolism, initiate immediate anticoagulation with a direct oral anticoagulant (DOAC)—specifically rivaroxaban or apixaban as single-drug regimens—which are now preferred over warfarin and low-molecular-weight heparin combinations. 1, 2

Risk Stratification Determines Treatment Intensity

Treatment selection depends critically on hemodynamic status at presentation:

• High-risk PE: Systolic hypotension (<90 mmHg), cardiogenic shock, or need for vasopressors 2, 3
• Intermediate-risk PE: Hemodynamically stable but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 2, 3
• Low-risk PE: Hemodynamically stable without RV dysfunction or myocardial injury 2, 3

High-Risk PE: Aggressive Intervention Required

For hemodynamically unstable patients, immediately administer unfractionated heparin (UFH) intravenously without waiting for diagnostic confirmation: 1, 2

• Initial bolus: 80 U/kg IV 2
• Continuous infusion: 18 U/kg/h 2
• Adjust based on aPTT to maintain 1.5-2.5 times control value (46-70 seconds) 2

Systemic thrombolytic therapy is mandatory for all high-risk PE patients unless absolute contraindications exist. 1, 3 Surgical pulmonary embolectomy should be performed when thrombolysis is contraindicated or has failed. 1, 3

Anticoagulation for Intermediate and Low-Risk PE

First-Line: Direct Oral Anticoagulants (DOACs)

DOACs are the preferred anticoagulant class over vitamin K antagonists for all eligible patients. 1, 2, 3

Rivaroxaban dosing (preferred single-drug regimen): 4, 5, 6

• 15 mg orally twice daily for 3 weeks
• Then 20 mg once daily for maintenance

Apixaban dosing (alternative single-drug regimen): 1, 2

• Higher dose during first week
• Then maintenance dosing

Dabigatran and edoxaban require at least 5-10 days of parenteral anticoagulation (LMWH or fondaparinux) before initiation. 4, 7

Alternative: Parenteral Anticoagulation Followed by Warfarin

If DOACs are not suitable, use LMWH or fondaparinux over UFH for hemodynamically stable patients: 1

• Enoxaparin: 1 mg/kg subcutaneously every 12 hours 8
• Fondaparinux (weight-adjusted): 8
  • <50 kg: 5 mg subcutaneously once daily
  • 50-100 kg: 7.5 mg subcutaneously once daily

  • 100 kg: 10 mg subcutaneously once daily

When transitioning to warfarin, overlap parenteral anticoagulation until INR reaches 2.5 (range 2.0-3.0) for 2 consecutive days. 1, 2, 4

Absolute Contraindications to DOACs

Do not use DOACs in the following situations: 1, 3

• Severe renal impairment (CrCl <30 mL/min)
• Pregnancy or lactation
• Antiphospholipid antibody syndrome (use warfarin indefinitely instead)

Special Populations

Cancer Patients

LMWH is the preferred initial and long-term treatment for cancer patients. 2, 3, 4 However, apixaban, edoxaban, and rivaroxaban are effective alternatives, except in patients with gastrointestinal cancer. 1, 7

Dalteparin dosing for cancer patients: 4

• 200 IU/kg once daily for 1 month
• Then 150 IU/kg once daily for 5 months

Pregnant Patients

Use therapeutic fixed doses of LMWH based on early pregnancy weight for hemodynamically stable pregnant women. 1, 3 Never use DOACs during pregnancy or lactation. 1

Critical timing considerations: 1

• Do not insert spinal/epidural needle within 24 hours of last LMWH dose
• Do not administer LMWH within 4 hours of epidural catheter removal

Duration of Anticoagulation

All patients with PE require therapeutic anticoagulation for at least 3 months. 1, 3, 7

After 3 months, duration depends on risk factors: 1, 2, 3

• Discontinue after 3 months: First PE secondary to major transient/reversible risk factor (e.g., surgery, trauma)
• Continue indefinitely:
  • Recurrent VTE (at least one previous episode of PE or DVT) not related to transient risk factor
  • Unprovoked PE
  • Active cancer or other persistent risk factors
  • Antiphospholipid antibody syndrome (must use warfarin, not DOAC)

For extended anticoagulation beyond 6 months, consider reduced-dose apixaban or rivaroxaban to balance efficacy and bleeding risk. 1, 7

Critical Pitfalls to Avoid

Never delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability. 1, 2, 4

Never stop parenteral anticoagulation before achieving therapeutic INR for 2 consecutive days when using warfarin. 2, 4

Avoid aggressive fluid resuscitation in high-risk PE, as it worsens right ventricular failure. 2, 4

Do not routinely use inferior vena cava filters—reserve only for absolute contraindications to anticoagulation or recurrent PE despite therapeutic anticoagulation. 1, 2

Multidisciplinary Management

For high-risk and selected intermediate-risk PE cases, establish multidisciplinary rapid-response teams (Pulmonary Embolism Response Teams) depending on hospital resources and expertise. 1, 3