What is the treatment for pulmonary embolism (PE)?

Treatment of Pulmonary Embolism

For hemodynamically stable PE, initiate a direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban immediately, as these are superior to warfarin with 0.6% lower bleeding rates and noninferior efficacy; for hemodynamically unstable PE (systolic BP <90 mmHg), administer IV unfractionated heparin with an 80 units/kg bolus plus systemic thrombolysis with alteplase unless absolute contraindications exist. 1, 2, 3

Immediate Risk Stratification

Risk stratification must be performed immediately upon PE diagnosis to determine treatment approach 2:

• High-risk (massive) PE: Systolic BP <90 mmHg, cardiac arrest, hemodynamic collapse requiring vasopressors, or cardiogenic shock 2
• Intermediate-risk (submassive) PE: Hemodynamically stable but with right ventricular dysfunction on imaging or elevated cardiac biomarkers 2
• Low-risk PE: Hemodynamically stable without RV dysfunction 2

High-Risk PE Management

Initiate IV unfractionated heparin immediately without delay with an 80 units/kg bolus followed by continuous infusion of 400-600 units/kg daily, titrated to maintain APTT 1.5-2.5 times control values 1, 2. Do not use LMWH or fondaparinux in hemodynamically unstable patients—only unfractionated heparin has been studied in this setting 2.

Administer systemic thrombolysis unless absolute contraindications exist, as it reduces mortality from 3.9% to 2.3% (1.6% absolute reduction) 2, 3:

• If cardiac arrest is imminent: 50 mg alteplase IV bolus 2
• If patient is more stable: 100 mg alteplase over 90 minutes 2

Absolute contraindications to thrombolysis include hemorrhagic stroke at any time, ischemic stroke in preceding 6 months, CNS damage/neoplasms, recent major trauma/surgery/head injury, GI bleeding within last month, and known active bleeding 2.

If thrombolysis is contraindicated or fails, perform surgical pulmonary embolectomy 1. Catheter embolectomy or thrombus fragmentation may be considered if surgery is not immediately available 1.

Hemodynamically Stable PE: Anticoagulation Strategy

Initial Parenteral Anticoagulation (if not using DOAC monotherapy)

Prefer low molecular weight heparin (LMWH) or fondaparinux over unfractionated heparin for initial parenteral anticoagulation 1, 2:

• Enoxaparin: 1 mg/kg subcutaneously every 12 hours 2, 4
• Fondaparinux: 5 mg if <50 kg, 7.5 mg if 50-100 kg, 10 mg if >100 kg (all once daily subcutaneously) 2, 4

Oral Anticoagulation

Direct oral anticoagulants (DOACs) are preferred over warfarin 1, 2, 3:

• Apixaban: FDA-approved for PE treatment 5
• Rivaroxaban: 15 mg twice daily with food for 21 days, then 20 mg once daily with food 6
• Edoxaban or dabigatran are also options 1, 2

DOACs have 0.6% lower bleeding rates compared to warfarin with noninferior efficacy 2, 3.

If warfarin is used instead: Overlap with parenteral anticoagulation for minimum 5-7 days until INR reaches 2.0-3.0 for two consecutive days, then continue warfarin targeting INR 2.5 (range 2.0-3.0) 1, 4.

DOAC Contraindications

Do not use DOACs in 1, 2:

• Severe renal impairment (CrCl <15-30 mL/min depending on agent)
• Pregnancy
• Antiphospholipid antibody syndrome (use warfarin indefinitely in these patients) 1

Duration of Anticoagulation

All patients require minimum 3 months of therapeutic anticoagulation 1, 2, 4.

Provoked PE (secondary to major transient/reversible risk factor)

Discontinue anticoagulation after 3 months 1, 2.

Unprovoked PE

Consider indefinite anticoagulation if bleeding risk is low-to-moderate 2, 4:

• Low bleeding risk features: Age <70 years, no previous bleeding episodes, no concomitant antiplatelet therapy, no renal or hepatic impairment, good medication adherence 4
• Recurrence risk after stopping: >5% annually, with approximately 50% experiencing recurrence within 10 years 4

High-risk features favoring indefinite therapy 2:

• Second episode of unprovoked PE
• Documented antiphospholipid antibodies or multiple thrombophilic conditions
• Active cancer
• Deficiency of antithrombin, Protein C, or Protein S
• Factor V Leiden or prothrombin 20210 gene mutation

High bleeding risk features favor stopping at 3-6 months: Age ≥80 years, previous major bleeding episodes, recurrent falls, need for dual antiplatelet therapy, severe renal or hepatic impairment 4.

Special Populations

Cancer patients: Require LMWH monotherapy for minimum 3-6 months with consideration of indefinite therapy while cancer remains active, as cancer carries 20% recurrence rate in first 12 months 4.

Recurrent unprovoked PE: Strongly recommend indefinite anticoagulation 4.

Outpatient vs. Inpatient Management

Low-risk patients may be candidates for outpatient management using validated risk scores (PESI class I/II, sPESI 0, or Hestia criteria) 2.

Exclusion criteria mandating hospital admission 2:

• Heart rate >110 bpm or systolic BP <100 mmHg
• Oxygen saturation <90% on room air
• Active bleeding or high bleeding risk
• Severe pain requiring opiates
• Other medical comorbidities requiring admission

Follow-Up Care

Routine clinical re-evaluation at 3-6 months post-PE is essential to assess for persistent dyspnea or functional limitation that may indicate chronic thromboembolic pulmonary hypertension (CTEPH) 2, 7.

Reassess risk-benefit ratio at regular intervals during indefinite anticoagulation, including drug tolerance, adherence, hepatic and renal function, and bleeding risk 1.

Critical Pitfalls to Avoid

Never delay anticoagulation in high-risk PE while awaiting confirmatory imaging if clinical suspicion is high 2, 7. Initiate anticoagulation while diagnostic workup is in progress if clinical probability is high or intermediate 1.

Do not use LMWH or fondaparinux in hemodynamically unstable patients—only unfractionated heparin has been studied in this setting 2.

Avoid stopping anticoagulation prematurely in unprovoked PE, as recurrence risk persists indefinitely and benefit only continues while on therapy 4.

Do not use reduced-intensity anticoagulation routinely, as it is less effective than conventional intensity 4.

Monitor platelet count if heparin continued beyond 5 days due to risk of heparin-induced thrombocytopenia 2.

Do not routinely use inferior vena cava filters 1.

Avoid aggressive fluid challenges in PE patients with right ventricular dysfunction 7.