Is Eliquis (apixaban) safe in patients with Chronic Kidney Disease (CKD) stage 4?

From the Guidelines

Eliquis (apixaban) can be used with caution in patients with CKD stage 4, but at a reduced dose of 2.5 mg twice daily, as recommended by the most recent guidelines 1. For patients with CKD stage 4 (estimated glomerular filtration rate of 15-29 mL/min), this dose adjustment is necessary to prevent excessive anticoagulation and bleeding risk. Additionally, patients should meet at least two of the following criteria to qualify for this reduced dose: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. Regular monitoring of kidney function is essential while on this medication. Compared to warfarin, Eliquis may offer a better safety profile in terms of bleeding risk for CKD patients, though the benefit-risk assessment should be individualized 1. Eliquis is primarily metabolized by the liver with partial renal excretion, which is why it can still be used in advanced kidney disease with appropriate dose adjustments, unlike some other direct oral anticoagulants that have higher renal clearance and may be contraindicated in severe CKD. Some key points to consider when using Eliquis in CKD stage 4 patients include:

• Close monitoring of renal function and adjustment of the dose as needed
• Assessment of the patient's overall clinical condition and individualized decision-making
• Consideration of the potential benefits and risks of anticoagulation therapy in the context of CKD
• Regular follow-up and reassessment of the patient's condition to ensure the safest and most effective use of Eliquis. It's also important to note that the use of Eliquis in patients with severe CKD (CrCl <15 mL/min) is not well established, and caution should be exercised when using this medication in these patients 1.

From the FDA Drug Label

The recommended dose is 2.5 mg twice daily in patients with at least two of the following characteristics [see Dosage and Administration (2.1)]: • age greater than or equal to 80 years • body weight less than or equal to 60 kg • serum creatinine greater than or equal to 1. 5 mg/dL

Clinical efficacy and safety studies with apixaban did not enroll patients with ESRD on dialysis or patients with a CrCl <15 mL/min; therefore, dosing recommendations are based on pharmacokinetic and pharmacodynamic (anti-FXa activity) data in subjects with ESRD maintained on dialysis [see Clinical Pharmacology (12.3)].

The safety of Eliquis (apixaban) in patients with Chronic Kidney Disease (CKD) stage 4 is not directly addressed in the drug label. However, the label provides dosing recommendations for patients with renal impairment, including those with serum creatinine greater than or equal to 1.5 mg/dL.

• For patients with nonvalvular atrial fibrillation, a reduced dose of 2.5 mg twice daily is recommended if they have at least two of the following characteristics: age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5 mg/dL.
• For patients with end-stage renal disease (ESRD) on dialysis, the label states that administration of apixaban at the usually recommended dose will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in clinical studies, but it is not known whether these concentrations will lead to similar stroke reduction and bleeding risk.
• The label also states that no dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis, for other indications such as prophylaxis of deep vein thrombosis following hip or knee replacement surgery, and treatment of DVT and PE. Based on the available information, it can be inferred that Eliquis may be used in patients with CKD stage 4, but the dosing recommendations should be individualized based on the patient's specific characteristics, such as age, body weight, and serum creatinine level 2.

From the Research

Safety of Eliquis in CKD Stage 4

The safety of Eliquis (apixaban) in patients with Chronic Kidney Disease (CKD) stage 4 has been evaluated in several studies.

• A meta-analysis published in 2018 3 found that apixaban was associated with a lower risk of major bleeding compared to warfarin in patients with advanced CKD or end-stage renal disease (ESRD).
• A retrospective cohort study published in 2018 4 found that patients with CKD stage 4 who took apixaban had similar bleeding rates at 3 months compared to those who took warfarin, but had lower major bleeding rates between 6 and 12 months.
• Another study published in 2020 5 found no difference in major bleeding between apixaban and warfarin in patients with CKD stage 4, but found increased rates of minor bleeding and composite bleeding in patients receiving warfarin.
• A systematic review published in 2022 6 found that apixaban had similar efficacy to warfarin for preventing stroke, systemic embolization, and recurrent venous thromboembolism, but had an equivalent or better safety profile concerning bleeding.
• A review of pharmacokinetic, interventional, and observational study data published in 2024 7 found that apixaban has a favorable clinical efficacy and safety profile compared to vitamin K antagonists for patients with atrial fibrillation or venous thromboembolism and comorbid kidney impairment.

Key Findings

• Apixaban is associated with a lower risk of major bleeding compared to warfarin in patients with advanced CKD or ESRD 3.
• Apixaban has similar efficacy to warfarin for preventing stroke, systemic embolization, and recurrent venous thromboembolism 6.
• Apixaban has an equivalent or better safety profile concerning bleeding compared to warfarin 4, 5, 6.
• Apixaban can be considered a reasonable alternative to warfarin in patients with CKD stage 4 or 5, including those on dialysis 5, 6.