What are the further treatment options for a patient with heart failure (HF) with an ejection fraction (EF) of 5-10%, who has biventricular thrombi while on heparin (Heparin) infusion and develops a stroke, previously noncompliant with Apixaban (apixaban), and now requiring alternative anticoagulation?

From the Guidelines

For patients with severe heart failure (EF 5-10%) who have biventricular thrombi while on heparin infusion and who have developed a stroke, therapeutic anticoagulation with factor Xa inhibitors, such as apixaban or rivaroxaban, is recommended over warfarin due to their more predictable anticoagulation effects and fewer drug-drug interactions. In this case, measuring factor Xa levels is suggested to ensure therapeutic anticoagulation, especially given the patient's previous non-compliance with apixaban 1. The 2022 AHA/ACC/HFSA guideline for the management of heart failure supports the use of factor Xa inhibitors, such as apixaban, rivaroxaban, and edoxaban, as they do not require routine anticoagulation monitoring or dose adjustment, simplifying patient management 1.

Key Considerations

• Factor Xa inhibitors provide a more predictable anticoagulation effect compared to warfarin, with fewer drug-drug interactions and no need for regular INR monitoring.
• Measuring factor Xa levels can help confirm that therapeutic anticoagulation is achieved, particularly important in high-risk patients with biventricular thrombi and stroke despite heparin therapy.
• Resuming apixaban at a dose of 5mg twice daily (or 2.5mg twice daily if dose-reduction criteria are met) would be appropriate, with close monitoring of adherence.
• Addressing the underlying severe heart failure with optimization of guideline-directed medical therapy, consideration for advanced therapies like LVAD or heart transplantation evaluation, and implementing strategies to improve medication adherence are essential components of management.

Anticoagulation Therapy

The choice of anticoagulant therapy should be based on the risk of thromboembolism, irrespective of whether the AF pattern is paroxysmal, persistent, or permanent 1. For patients with AF, anticoagulant therapy should be individualized on the basis of shared decision-making after discussion of the absolute risks and relative risks of stroke and bleeding, as well as the patient’s values and preferences 1.

Monitoring and Adherence

Regular monitoring of factor Xa levels and adherence to anticoagulation therapy is crucial in patients with severe heart failure and biventricular thrombi, especially those with a history of non-compliance 1. Implementing strategies to improve medication adherence, such as patient education and counseling, can help ensure that patients receive the full benefits of anticoagulation therapy.

From the FDA Drug Label

The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the particular patient’s PT/INR response to the drug. The dose of warfarin should be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations.

For a patient with heart failure (HF) and biventricular thrombi who developed a stroke while on heparin, and was previously noncompliant with apixaban, warfarin may be considered as a treatment option.

• The patient's INR levels should be monitored and the warfarin dose adjusted accordingly to maintain a target INR of 2.0-3.0.
• The decision to use warfarin should be based on the patient's individual risk-benefit assessment, taking into account their history of stroke, heart failure, and noncompliance with previous anticoagulation therapy 2.
• Xa levels may not be directly relevant to warfarin therapy, as warfarin works by inhibiting vitamin K-dependent clotting factors, whereas Xa levels are more relevant to factor Xa inhibitors such as apixaban.

From the Research

Treatment Options for Patients with HF (EF 5-10)

• For patients with heart failure and reduced ejection fraction, the use of anticoagulation therapy is a topic of ongoing research and debate 3, 4.
• The novel oral anticoagulants (NOACs) have been shown to have at least equivalent efficacy in reducing stroke as warfarin while exposing patients to a lower risk of bleeding 3.
• Rivaroxaban, a factor Xa inhibitor, has been studied in patients with heart failure and nonvalvular atrial fibrillation, and has been found to be noninferior to warfarin for the prevention of stroke and systemic embolic events 5.
• However, in patients with heart failure and sinus rhythm, the use of rivaroxaban has not been shown to significantly reduce the risk of death, myocardial infarction, or stroke compared to placebo 6.

Monitoring and Adjusting Anticoagulation Therapy

• The attending's suggestion to get Xa levels may be related to the fact that the patient was previously on apixaban, a NOAC, and was noncompliant 3.
• Monitoring Xa levels can help determine the effectiveness of anticoagulation therapy and adjust the dose as needed 3.
• However, the decision to use warfarin or a NOAC, such as rivaroxaban, should be based on individual patient factors, including the risk of stroke and bleeding, and the patient's ability to adhere to the prescribed treatment regimen 7, 4.

Considerations for Patients with Biventricular Thrombi and Stroke

• The presence of biventricular thrombi and a history of stroke increases the risk of further thromboembolic events, and anticoagulation therapy should be carefully considered 3, 4.
• The choice of anticoagulant and the intensity of anticoagulation should be individualized based on the patient's risk factors and clinical presentation 5, 7.
• Close monitoring and follow-up are essential to ensure the effectiveness and safety of anticoagulation therapy in these high-risk patients 6, 4.