What is the next best step for a patient with a history of atrial fibrillation (AF) who presents with a recurrent pulmonary embolus (PE) despite being on warfarin (coumarin) with a therapeutic International Normalized Ratio (INR) of 2.5?

From the Guidelines

The next best step for this patient is to switch from warfarin to a direct oral anticoagulant (DOAC) such as rivaroxaban, apixaban, or edoxaban. Despite being on therapeutic warfarin with an INR of 2.5, the patient has experienced recurrent pulmonary emboli, indicating treatment failure. According to the 2024 ESC guidelines for the management of atrial fibrillation 1, DOACs are preferred over vitamin K antagonists (VKAs) like warfarin, except in patients with mechanical heart valves and mitral stenosis. The guidelines recommend using full standard doses for DOACs unless the patient meets specific dose-reduction criteria. Rivaroxaban would typically be dosed at 15 mg twice daily for 21 days followed by 20 mg once daily, apixaban at 10 mg twice daily for 7 days followed by 5 mg twice daily, or edoxaban at 60 mg once daily (after initial parenteral anticoagulation). DOACs have been shown to be at least as effective as warfarin for preventing recurrent venous thromboembolism with a better safety profile and fewer drug interactions, as supported by the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.

Some key points to consider in the management of this patient include:

• Further evaluation to rule out underlying causes of anticoagulation failure, such as antiphospholipid syndrome, malignancy, or anatomical abnormalities
• Management of comorbidities and risk factors, such as hypertension, heart failure, diabetes mellitus, obesity, obstructive sleep apnoea, physical inactivity, and high alcohol intake, as recommended in the 2024 ESC guidelines 1
• Assessment of the risk of thromboembolism using locally validated risk tools or the CHA2DS2-VA score, with reassessment at periodic intervals to assist in decisions on anticoagulant prescription
• Consideration of other options, such as increasing the DOAC dose, adding an antiplatelet agent, or considering an inferior vena cava filter placement, if the patient continues to have recurrent emboli despite DOAC therapy.

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.

2.4 Converting from or to apixaban Switching from warfarin to apixaban: Warfarin should be discontinued and apixaban started when the international normalized ratio (INR) is below 2.0.

The next best step is to switch from warfarin to apixaban since the patient has had recurrent pulmonary emboli while on warfarin. However, the patient's current INR is 2.5, which is above the recommended threshold of 2.0 for switching to apixaban. Therefore, wait until the INR is below 2.0 before starting apixaban. The recommended dose of apixaban for reducing the risk of recurrent DVT and PE is 2.5 mg twice daily after at least 6 months of treatment for DVT or PE, but initially, the dose is 10 mg taken orally twice daily for the first 7 days of therapy, then 5 mg taken orally twice daily 2.

From the Research

Patient Profile

• The patient has a history of atrial fibrillation and has experienced 3 pulmonary emboli in the past 8 months.
• The patient has been on warfarin for the past year with a most recent INR of 2.5.

Current Treatment and Considerations

• Warfarin has been the most commonly prescribed oral anticoagulant, but it has disadvantages such as dietary interactions and frequent laboratory monitoring 3.
• Direct oral anticoagulants (DOACs) have been introduced as safer and equally effective alternatives to warfarin 3, 4, 5.
• The patient's history of recurrent pulmonary embolus despite being on warfarin suggests that switching to a DOAC may be considered.

Switching to DOACs

• Studies have shown that DOACs have superior efficacy and a better adverse effect profile compared to warfarin 5, 6.
• Factors that affect the time to switch from warfarin to a DOAC include female sex, age, history of prior stroke or transient ischemic attack, and insurance status 7.
• The patient's history of recurrent pulmonary embolus and atrial fibrillation may be indicative of a need to switch to a DOAC.

Next Best Step

• Considering the patient's history and current treatment, switching to a DOAC such as apixaban, dabigatran, or rivaroxaban may be the next best step 6.
• The choice of DOAC should be based on the patient's individual characteristics, such as renal function and bleeding risk 5.
• Close monitoring of the patient's response to the new anticoagulant and adjustment of the treatment plan as needed is crucial.