Should patients with chronic pulmonary embolism (PE) on Xarelto (rivaroxaban) be heparinized upon admission?

From the Guidelines

Patients with chronic pulmonary embolism (PE) on Xarelto (rivaroxaban) should not be heparinized upon admission, as the current anticoagulant therapy is already effective and heparinization is not recommended for patients on direct oral anticoagulants (DOACs) like rivaroxaban.

Rationale

• The Chest guidelines recommend apixaban, dabigatran, edoxaban, or rivaroxaban over vitamin K antagonists (VKAs) as treatment-phase anticoagulant therapy for patients with acute VTE, including PE 1.
• The guidelines also suggest that there is no need to change the choice of anticoagulant after the first 3 months of treatment 1.
• Initial parenteral anticoagulant therapy is recommended for acute DVT or PE, but this is not applicable to patients already on rivaroxaban, a DOAC that does not require heparinization 1.

Key Points

• Rivaroxaban is a direct oral anticoagulant (DOAC) that does not require heparinization.
• The Chest guidelines recommend DOACs over VKAs for treatment-phase anticoagulant therapy in patients with acute VTE.
• Patients with chronic PE on rivaroxaban should continue their current anticoagulant therapy without the need for heparinization.

From the FDA Drug Label

1. 9 Acute PE in Hemodynamically Unstable Patients or Patients Who Require Thrombolysis or Pulmonary Embolectomy 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.

Patients with chronic pulmonary embolism (PE) on Xarelto (rivaroxaban) should be heparinized upon admission if they present with hemodynamic instability or require thrombolysis or pulmonary embolectomy. However, the label does not provide direct guidance for patients with chronic PE who are stable. Therefore, a conservative approach would be to consider heparinization in these patients, but the decision should be made on a case-by-case basis, taking into account the individual patient's risk factors and clinical presentation 2.

Key points:

• Heparinization is recommended for patients with PE who present with hemodynamic instability or require thrombolysis or pulmonary embolectomy.
• The label does not provide direct guidance for stable patients with chronic PE.
• A conservative approach would be to consider heparinization in stable patients with chronic PE, but the decision should be made on a case-by-case basis.

From the Research

Heparinization in Patients with Chronic Pulmonary Embolism on Xarelto

• The decision to heparinize patients with chronic pulmonary embolism (PE) on Xarelto (rivaroxaban) upon admission is a complex one, and the available evidence provides some insights into this issue.
• A study published in 2014 3 found that "safe dose" thrombolysis plus rivaroxaban is highly safe and effective in the treatment of moderate and severe PE, leading to favorable early and intermediate-term outcomes and early discharge. In this study, heparin was given for a total of 24 hours and rivaroxaban was started at 15 or 20 mg daily 2 hours after termination of heparin infusion.
• Another study published in 2020 4 compared the efficacy and safety of rivaroxaban versus warfarin for the treatment of acute pulmonary embolism and found that there was no significant difference in thrombus absorption between rivaroxaban and standard therapy (which included low-molecular-weight heparin combined with warfarin).
• A study published in 2016 5 found that patients with acute pulmonary embolism who were treated with rivaroxaban had a shorter duration of hospitalization compared to those treated with standard therapy (which included unfractionated heparin, low-molecular-weight heparin, or vitamin K antagonists).
• However, a study published in 2022 6 found that patients with severe PE who received off-label rivaroxaban (i.e., delayed start or low doses) had a worse outcome than those on labeled rivaroxaban, with higher rates of major bleeding and death.

Key Findings

• The use of heparin in combination with rivaroxaban may be beneficial in certain patients with chronic PE, particularly those with severe disease or those who require thrombolysis.
• Rivaroxaban monotherapy may be a viable option for patients with chronic PE, with a shorter duration of hospitalization and similar efficacy and safety compared to standard therapy.
• However, the use of off-label rivaroxaban (i.e., delayed start or low doses) may be associated with a worse outcome, and therefore should be used with caution.

Clinical Implications

• Clinicians should carefully consider the individual patient's risk factors and clinical presentation when deciding whether to heparinize patients with chronic PE on Xarelto upon admission.
• The use of rivaroxaban monotherapy or in combination with heparin should be guided by the patient's specific clinical needs and the availability of evidence-based guidelines.