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

From the Guidelines

Anticoagulation is essential for treating pulmonary embolism (PE) to prevent clot extension and recurrence, and the most recent guidelines recommend initiating anticoagulation with low molecular weight heparin (LMWH) or unfractionated heparin without delay in patients with high-risk PE 1. For initial treatment, LMWH such as enoxaparin 1 mg/kg twice daily or 1.5 mg/kg once daily is recommended, or unfractionated heparin with a bolus of 80 units/kg followed by 18 units/kg/hour infusion, adjusted to maintain aPTT at 1.5-2.5 times normal. Some key points to consider in the management of PE include:

• The use of direct oral anticoagulants (DOACs) is preferred for most patients without cancer for long-term treatment, with options including rivaroxaban, apixaban, edoxaban, or dabigatran 1.
• For cancer-associated PE, LMWH or specific DOACs like edoxaban or rivaroxaban are preferred 1.
• Standard treatment duration is 3 months for provoked PE and at least 6-12 months for unprovoked PE, with consideration for indefinite therapy in recurrent or high-risk cases 1.
• 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. It is also important to note that:
• Rescue thrombolytic therapy is recommended for patients with haemodynamic deterioration on anticoagulation treatment 1.
• As an alternative to rescue thrombolytic therapy, surgical embolectomy or percutaneous catheter-directed treatment should be considered for patients with haemodynamic deterioration on anticoagulation treatment 1.
• Routine use of primary systemic thrombolysis is not recommended in patients with intermediate- or low-risk PE 1. Overall, the goal of anticoagulation therapy in PE is to prevent new clot formation and allow the body's natural fibrinolytic system to dissolve existing clots, reducing the risk of recurrent thromboembolism and death.

From the FDA Drug Label

To reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation (1. 1) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in adult patients who have been treated with a parenteral anticoagulant for 5 to 10 days (1.2) To reduce the risk of recurrence of DVT and PE in adult patients who have been previously treated (1. 3)

Anticoagulation for PE can be achieved with dabigatran etexilate capsules.

• The recommended dose is 150 mg orally, twice daily after 5 to 10 days of parenteral anticoagulation for patients with CrCl >30 mL/min.
• It is essential to note that dabigatran etexilate capsules are not substitutable on a milligram-to-milligram basis with other dabigatran etexilate dosage forms.
• Patients should be closely monitored for signs and symptoms of bleeding, as dabigatran etexilate capsules can cause serious and fatal bleeding 2.

Alternatively, rivaroxaban can also be used for the treatment of pulmonary embolism (PE), however the provided label does not specify the exact dosage for this particular use case, only that initiation of XARELTO is not recommended acutely as an alternative to unfractionated heparin in patients with pulmonary embolism who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy 3.

From the Research

Anticoagulation for Pulmonary Embolism (PE)

• Anticoagulation is a crucial treatment for patients with pulmonary embolism (PE), aiming to prevent death, reduce morbidity, and prevent thromboembolic pulmonary hypertension 4, 5.
• The choice of anticoagulant agent depends on the patient's clinical probability of PE, with unfractionated heparin (UFH) used in hemodynamically unstable patients and low molecular weight heparins (LMWH) or fondaparinux in normotensive patients 4.
• Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, rivaroxaban, and dabigatran are non-inferior to heparin combined with a vitamin K antagonist for treating PE and have a lower rate of bleeding 6, 7.

Duration of Anticoagulation

• The duration of anticoagulation should be individualized, considering both the risk of PE recurrence and the risk of bleeding 4.
• Patients with a strong transient risk factor have a low risk of recurrence and can discontinue anticoagulation after three months, while those with a strong persistent risk factor (such as active cancer) have a high risk of recurrence and should receive anticoagulant treatment of indefinite duration 4.

Comparison of Anticoagulants

• Dabigatran has been shown to be comparable in effectiveness to warfarin, with a greater safety profile in terms of bleeding events 8.
• Rivaroxaban has been demonstrated to be non-inferior to standard of care (enoxaparin/VKA) for the treatment of patients with acute symptomatic PE, with significantly lower rates of major bleeding 6.

Treatment Guidelines

• The European Society of Cardiology (ESC) recommends that all eligible patients with PE be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA) 4.
• The American College of Chest Physicians (ACCP) recommends the use of DOACs as first-line therapy for patients with PE, with thrombolysis reserved for patients with systolic blood pressure lower than 90 mm Hg 7.