What are the risks of bleeding vs clotting in patients taking Eliquis (apixaban) at a dose of 2.5 mg twice daily?

From the Guidelines

Eliquis (apixaban) at a dose of 2.5 mg twice daily poses a significant risk of bleeding, including gastrointestinal bleeding and intracranial hemorrhage, which outweighs the risk of clotting in most patients, particularly those with at least two of the following factors: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. The primary risk associated with Eliquis at this dose is increased bleeding due to its anticoagulant effects that inhibit Factor Xa in the clotting cascade. This reduced dose is typically prescribed for patients with higher bleeding risk, as evidenced by the 2024 guideline for the diagnosis and management of atrial fibrillation 1. Despite anticoagulation, breakthrough clotting events can still occur, particularly if the dose is insufficient for the patient's condition or if they have very high thrombotic risk factors. Patients should be vigilant for signs of bleeding (unusual bruising, blood in urine/stool, severe headache) and clotting (swelling, pain, redness in limbs, chest pain, shortness of breath), as supported by the study on the use of direct oral anticoagulants for primary thromboprophylaxis in ambulatory cancer patients 1. Regular monitoring by healthcare providers is essential, and patients should inform all healthcare providers about taking this medication, especially before procedures. Patients should avoid NSAIDs when possible and limit alcohol consumption to reduce bleeding risk while maintaining consistent dosing without skipping doses to prevent clotting complications, as recommended in the update on antithrombotic therapy and body mass 1. Additionally, the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation provides further guidance on the use of apixaban in patients with atrial fibrillation, including dosing recommendations for patients with severe kidney disease 1. Key considerations for patients taking Eliquis at a dose of 2.5 mg twice daily include:

• Monitoring for signs of bleeding and clotting
• Avoiding NSAIDs and limiting alcohol consumption
• Informing all healthcare providers about taking this medication
• Maintaining consistent dosing without skipping doses
• Regular monitoring by healthcare providers.

From the FDA Drug Label

Apixaban can cause bleeding which can be serious and rarely may lead to death. You may have a higher risk of bleeding if you take apixaban tablets and take other medicines that increase your risk of bleeding... Apixaban lowers your chance of having a stroke by helping to prevent clots from forming If you stop taking apixaban, you may have increased risk of forming a clot in your blood.

The risk of bleeding vs clotting in patients taking Eliquis (apixaban) at a dose of 2.5 mg twice daily is that apixaban can cause bleeding which can be serious, but it also lowers the chance of having a stroke by preventing clots from forming.

• Bleeding risks are increased if patients take other medicines that increase the risk of bleeding.
• Clotting risks are increased if patients stop taking apixaban without talking to their doctor. 2

From the Research

Risks of Bleeding vs Clotting with Eliquis (Apixaban) at 2.5 mg

The risks of bleeding vs clotting in patients taking Eliquis (apixaban) at a dose of 2.5 mg twice daily have been evaluated in several studies.

• The study by 3 found that during 30 months of treatment with low-dose apixaban, 14 patients (7.6%) experienced recurrent venous thromboembolism (VTE), 6 patients (3.1%) experienced major bleeding, and 16 patients (8.1%) experienced clinically relevant non-major bleeding.
• Another study by 4 compared the effectiveness and safety of low-dose (2.5 mg twice daily) versus full-dose (5 mg twice daily) apixaban during extended phase oral anticoagulation in patients with VTE, and found no detected differences in recurrent VTE or major bleeding events between the two groups.
• A study by 5 evaluated the efficacy and safety of apixaban versus enoxaparin for thromboprophylaxis in medically ill patients, and found that apixaban was associated with significantly more major bleeding events than enoxaparin.
• The study by 6 found that the 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively, whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively.
• The study by 7 found that patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared to patients without these characteristics.

Key Findings

• Low-dose apixaban (2.5 mg twice daily) may be an alternative option for extended phase therapy for risk reduction of VTE recurrence compared to full-dose apixaban (5 mg twice daily) 4.
• Apixaban is associated with a higher risk of major bleeding events compared to enoxaparin in medically ill patients 5.
• The risk of recurrent VTE and major bleeding events is higher in patients with advanced age, low body weight, or renal dysfunction 7.
• Clinically relevant bleeding events are approximately 10-fold more frequent than stroke or systemic embolism among patients with atrial fibrillation and end-stage kidney disease on hemodialysis 6.