What are the recommendations for anticoagulation therapy in patients with recurrent Pulmonary Embolism (PE)?

From the Guidelines

For recurrent pulmonary embolism (PE), indefinite anticoagulation therapy is strongly recommended. According to the most recent guidelines, direct oral anticoagulants (DOACs) are the preferred first-line agents, including apixaban, rivaroxaban, edoxaban, or dabigatran 1. The recommended dosages are apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) after 6 months of therapeutic anticoagulation 1. Low molecular weight heparins (LMWH) such as enoxaparin or warfarin are alternatives when DOACs are contraindicated.

For patients with recurrent PE despite therapeutic anticoagulation, options include:

• Switching to a different anticoagulant class
• Increasing the DOAC dose (e.g., apixaban to 10mg twice daily)
• Adding an inferior vena cava filter, although this is generally not recommended 1 Patients with active cancer should receive LMWH (enoxaparin 1mg/kg twice daily) or specific DOACs (rivaroxaban or edoxaban) for at least 6 months, then reassess 1. Antiphospholipid syndrome patients typically require warfarin with a higher target INR of 2.5-3.5.

Regular monitoring for bleeding complications, medication adherence assessment, and evaluation for underlying causes of recurrence are essential components of management. The rationale for indefinite therapy is that recurrent PE indicates a significant ongoing thrombotic risk that outweighs bleeding risks in most patients. The patient’s bleeding risk should be assessed to identify and treat modifiable bleeding risk factors, and it may influence decision-making on the duration and regimen/dose of anticoagulant treatment 1.

From the FDA Drug Label

1.5 Reduction in the Risk of Recurrence of DVT and PE

Apixaban tablets are indicated to reduce the risk of recurrent DVT and PE following initial therapy.

• The recommended use of apixaban is to reduce the risk of recurrent DVT and PE.
• Apixaban can be used for the treatment of recurrent PE as part of the reduction in the risk of recurrence of DVT and PE following initial therapy 2.

From the Research

Recommendations for Anticoagulation for Recurrent PE

• The use of antithrombotic therapy can prevent recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE), but it is associated with an increased risk for major bleeding 3.
• For the primary treatment of unprovoked VTE, VTE provoked by chronic risk factors or transient risk factors, treating patients with a longer course (>6 months) of anticoagulation probably reduces recurrent PE and DVT, but it is associated with increased mortality and a higher risk for major bleeding 3.
• For the secondary prevention of unprovoked VTE and VTE provoked by chronic risk factors, indefinite anticoagulation therapy is associated with decreased mortality, a reduction in recurrent PE and DVT, and an increase in the risk for bleeding 3.
• Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for the treatment of patients with acute pulmonary thromboembolism (PTE) 4.
• Anticoagulant treatment reduces recurrent venous thromboembolism (VTE) by about 90% after index pulmonary embolism, but the main counterbalance for life-long anticoagulation is the risk for anticoagulants-associated bleeding 5.
• The choice of anticoagulation management includes direct oral anticoagulants, with vitamin K antagonists and low-molecular-weight heparin preferred in special populations or selected patients 6.
• Outpatient treatment with LMWH has been shown to be feasible in many patients, and offers the potential for cost-savings and improvements in health-related quality of life 7.

Anticoagulant Options

• Direct oral anticoagulants are the preferred choice of anticoagulation management 6.
• Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients 6.
• Low-molecular-weight heparin is at least as effective as unfractionated heparin in the treatment of PE, with a similar risk of bleeding 7.

Considerations for Anticoagulation Management

• The risk for non-major clinically relevant bleeding with direct oral anticoagulants is not negligible and is probably higher than the risk for recurrence over time in several patient categories 5.
• The choice of extended anticoagulation should be carefully based on the balance between the estimated risk of recurrent VTE and that of bleeding 5.
• Special patient populations and risk factor considerations should be taken into account when making decisions about anticoagulation management 6.