From the Guidelines
Apixaban can cause drug-induced liver injury (DILI), although no signal for increased hepatotoxicity has been observed in any of the NOAC trials, including the 2018 European Heart Rhythm Association practical guide 1. When DILI from apixaban is suspected, the medication should be discontinued immediately and liver function tests monitored closely. Some key points to consider when managing DILI from apixaban include:
- Patients typically present with elevated liver enzymes (ALT, AST), sometimes accompanied by jaundice, fatigue, abdominal pain, or nausea.
- The liver injury pattern is usually hepatocellular but can be mixed or cholestatic.
- Most cases occur within the first few months of treatment.
- After discontinuation, liver function typically improves within weeks, though complete resolution may take months.
- Alternative anticoagulation should be considered based on the patient's indication, with options including warfarin, low molecular weight heparin, or other direct oral anticoagulants (though cross-sensitivity may occur). It is essential to note that patients with pre-existing liver disease, such as Child B liver cirrhosis, may be at higher risk and should be monitored more closely when starting apixaban therapy, as recommended by the 2018 European Heart Rhythm Association practical guide 1. Key considerations for managing apixaban in patients with liver disease include:
- Apixaban may be used with caution in patients with Child B cirrhosis.
- Rivaroxaban should not be used in AF patients with Child B liver cirrhosis due to increased drug exposure.
- Initiation and follow-up at a specialized centre in a multidisciplinary team (including a hepatologist and a hematologist) is recommended for patients with significant liver disease.
From the Research
Discontinuation of Apixaban
- Discontinuation rates of apixaban were found to be lower compared to warfarin in patients with atrial fibrillation, with a discontinuation rate of 21.4% for apixaban versus 23.4% for warfarin 2.
- A study comparing the discontinuation rates of apixaban, warfarin, dabigatran, and rivaroxaban in newly anticoagulated atrial fibrillation patients found that apixaban had the lowest discontinuation rate, with a hazard ratio of 0.57 compared to warfarin 3.
- The most common reasons for discontinuation of apixaban were patient request and adverse events, with no significant difference between treatment groups 2.
Clinical Outcomes After Discontinuation
- The cumulative incidence of clinical events ≤30 days after premature permanent discontinuation of apixaban for all-cause death, thromboembolism, myocardial infarction, and major bleeding was 5.8%, 2.6%, 0.9%, and 3.0%, respectively 2.
- No significant difference was seen between treatment groups with respect to clinical outcomes after discontinuation 2.
Comparison with Other Anticoagulants
- A systematic review and meta-analysis of subgroups found that apixaban, dabigatran, and rivaroxaban had a lower risk of intracranial bleeding compared to warfarin, but were not more effective in preventing non-hemorrhagic stroke and systemic embolic events 4.
- A study comparing the effectiveness of apixaban, dabigatran, and rivaroxaban found that apixaban was noninferior to vitamin K antagonists in the prevention of stroke and venous thromboembolism, with a good safety profile 5.