What are the contraindications for Direct Oral Anticoagulants (DOAC)?

From the Guidelines

Direct oral anticoagulants (DOACs) are contraindicated in several clinical scenarios, including active major bleeding, severe hypersensitivity, mechanical heart valves, and concurrent treatment with other anticoagulants, as well as in patients with severe renal impairment, moderate to severe hepatic impairment, and certain drug interactions, as evidenced by the most recent study 1. The contraindications for DOACs can be broken down into several key categories:

• Absolute contraindications: active major bleeding, severe hypersensitivity to the medication, mechanical heart valves (particularly for dabigatran), and concurrent treatment with other anticoagulants.
• Renal impairment: dabigatran is contraindicated when creatinine clearance is below 30 ml/min, while apixaban, rivaroxaban, and edoxaban require dose adjustments or avoidance in severe renal dysfunction.
• Hepatic impairment: moderate to severe hepatic impairment (particularly Child-Pugh B and C) is another contraindication, especially for rivaroxaban and edoxaban.
• Drug interactions: certain drug interactions pose significant risks, particularly with strong CYP3A4 and P-glycoprotein inhibitors like ketoconazole, itraconazole, and certain HIV protease inhibitors, as noted in 1 and 1. These contraindications exist because DOACs can increase bleeding risk in vulnerable populations, may not work effectively in certain conditions like mechanical valves, and their pharmacokinetics can be dangerously altered by organ dysfunction or drug interactions, as discussed in 1 and 1. Some specific considerations for individual DOACs include:
• Apixaban: should be avoided in patients with severe hepatic impairment, as it is primarily metabolized in the liver, as stated in 1.
• Edoxaban: renal clearance accounts for approximately 50% of the total clearance, and it should be used with caution in patients with moderate renal impairment, as noted in 1.
• Dabigatran: renal clearance is 80% of total clearance, and it should be avoided in patients with severe renal impairment, as discussed in 1.
• Rivaroxaban: primarily eliminated via the kidneys, and should be avoided in patients with severe renal impairment and used with caution in those with moderate impairment, as stated in 1.

From the FDA Drug Label

The use of dabigatran etexilate capsules are contraindicated in all patients with mechanical prosthetic valves Direct-acting oral anticoagulants (DOACs), including dabigatran etexilate capsules, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS) The safety and efficacy of apixaban tablets have not been studied in patients with prosthetic heart valves. Therefore, use of apixaban tablets is not recommended in these patients. Direct-acting oral anticoagulants (DOACs), including Apixaban Tablets, are not recommended for use in patients with triple-positive antiphospholipid syndrome (APS)

Contraindications for DOACs:

• Mechanical prosthetic valves 2
• Triple-positive antiphospholipid syndrome (APS) 2, 3
• Prosthetic heart valves for apixaban tablets 3

From the Research

DOAC Contraindications

• Patients with end-stage renal disease (ESRD) with or without dialysis are not approved for DOAC use 4
• Kidney transplant patients under immunosuppression with calcineurin inhibitors should not use DOACs, instead conventional therapy with vitamin K antagonists (VKA) is recommended 4
• Patients with severe renal impairment require careful monitoring of renal function before initiation and after start of DOAC therapy 4, 5
• DOACs are not recommended for patients with certain rare renal diseases and hypercoagulable states without careful consideration and monitoring 4
• Patients with advanced chronic liver disease require careful consideration before using DOACs due to increased risk of thromboembolism and bleeding 6

Special Considerations

• Accurate dosing of DOACs is crucial in patients with renal impairment to avoid ischemic events or bleeding 5, 7
• Patients with moderate to severe renal impairment may require dose adjustments for DOACs 5, 7
• Elderly patients, diabetics, and patients with preexisting kidney disease are at higher risk for acute renal failure and require careful monitoring 4