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 the preferred first-line agents over warfarin and low-molecular-weight heparin combinations. 1, 2

Risk Stratification Determines Treatment Approach

Treatment intensity must be guided by hemodynamic status and right ventricular function:

High-Risk PE (Hemodynamically Unstable):

• Characterized by systolic hypotension or cardiogenic shock requiring vasopressors 1, 2
• Immediately administer unfractionated heparin (UFH) intravenously without waiting for diagnostic confirmation: 80 U/kg IV bolus followed by continuous infusion at 18 U/kg/h 1, 3
• Adjust subsequent doses based on aPTT to maintain 1.5-2.5 times control value (46-70 seconds) 1, 3
• Systemic thrombolytic therapy is mandatory unless absolute contraindications exist 1, 2
• Surgical pulmonary embolectomy is recommended when thrombolysis is contraindicated or has failed 2

Intermediate-Risk PE (Hemodynamically Stable with RV Dysfunction):

• Defined by hemodynamic stability but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 1, 2
• Initiate anticoagulation with a DOAC or LMWH 1

Low-Risk PE (Hemodynamically Stable without RV Dysfunction):

• Characterized by hemodynamic stability without right ventricular dysfunction or myocardial injury 1, 2
• Initiate anticoagulation with a DOAC or LMWH 1

First-Line Anticoagulation Strategy

DOACs are preferred over vitamin K antagonists for all eligible patients 1, 2:

Rivaroxaban (FDA-approved for PE treatment):

• 15 mg orally twice daily for 3 weeks, then 20 mg once daily 3, 4
• No parenteral lead-in required 3

Apixaban (FDA-approved for PE treatment):

• Higher dose during the first week, then maintenance dosing 3, 5
• Particularly effective in cancer patients 3

Dabigatran:

• Requires at least 5-10 days of parenteral anticoagulation (LMWH or UFH) before initiation 3
• Non-inferior to warfarin with fewer bleeding episodes 3

Alternative Anticoagulation When DOACs Are Not Suitable

For patients ineligible for DOACs, use LMWH or fondaparinux followed by warfarin:

• Overlap parenteral anticoagulation with warfarin until INR reaches 2.5 for 2 consecutive days 3, 2
• Target INR range: 2.0-3.0 6
• Enoxaparin and tinzaparin are LMWH options; fondaparinux is used in a weight-adjusted manner 1

DOAC contraindications include:

• Severe renal impairment (creatinine clearance <30 mL/min for rivaroxaban, dabigatran, edoxaban; <25 mL/min for apixaban) 6, 2
• Pregnancy or lactation 2
• Antiphospholipid antibody syndrome 2

Special Populations Requiring Modified Approaches

Cancer Patients:

• LMWH is the preferred initial and long-term treatment 1, 2
• Dalteparin dosing: 200 IU/kg once daily for 1 month, then 150 IU/kg once daily for 5 months 6, 3
• Apixaban is an effective alternative 1, 3
• Cancer patients have approximately 20% recurrence rate during the first 12 months, making them candidates for indefinite anticoagulation 6

Pregnant Patients:

• Use therapeutic fixed doses of LMWH based on early pregnancy weight 1, 2
• All pregnant women with suspected or confirmed PE should be reviewed by a consultant and discussed with maternity services prior to discharge 1

Severe Renal Dysfunction:

• UFH is preferred when creatinine clearance is severely reduced 3

Duration of Anticoagulation

All patients require therapeutic anticoagulation for at least 3 months 6, 2:

Provoked PE (associated with transient/reversible risk factors):

• Discontinue anticoagulation after 3 months, provided the transient risk factor no longer exists 6, 1, 2
• Recurrence rate approximately 2.5% per year after discontinuation 6

Unprovoked PE:

• Continue anticoagulation indefinitely 1, 2
• Recurrence rate approximately 4.5% per year after discontinuation, up to 10% in the first year 6

Recurrent VTE or Antiphospholipid Antibody Syndrome:

• Indefinite anticoagulation is mandatory 1, 2
• For antiphospholipid antibody syndrome, use a vitamin K antagonist (not DOACs) 1, 2

Critical Pitfalls to Avoid

Never delay anticoagulation while awaiting diagnostic confirmation in patients with high or intermediate clinical probability 1, 3:

• The risk of withholding treatment outweighs the risk of bleeding in these scenarios 1

When using warfarin, never stop parenteral anticoagulation before achieving therapeutic INR for 2 consecutive days 1, 3:

• Warfarin initially creates a hypercoagulable state before achieving therapeutic anticoagulation 3

Avoid aggressive fluid resuscitation in high-risk PE:

• Fluid boluses can worsen right ventricular failure and hemodynamic collapse 1, 3

Do not routinely use inferior vena cava filters:

• Only consider filters for absolute contraindications to anticoagulation or recurrent PE despite therapeutic anticoagulation 1
• Filters are not indicated for patients who can be treated with anticoagulation 6