In this episode, I’ll discuss a study about the safety of apixaban in patients with renal insufficiency.
The US FDA and the European Medicines Agency have discordant recommendations for apixaban dosing in chronic kidney disease.
The US labeling states:
Anti-FXa activity adjusted for exposure to apixaban was similar across renal function categories.
Dosing is only adjusted downwards if a patient has at least two of the following 3 characteristics: age 80 or greater, weight 60 kg or less, and serum creatinine 1.5 or greater.
The European labeling states:
In patients with severe renal impairment…[taking apixaban] for the prevention of stroke and systemic embolism in patients with NVAF, patients should receive the lower dose of apixaban 2.5 mg twice daily.
A recent retrospective analysis published in Circulation attempted to compare the two dosing schemes.
Over 4000 elderly patients with a mean eGFR of 24 were analyzed. Using inverse probability of treatment weighting analysis, the US labeling recommendation of apixaban 5 mg was associated with a higher risk of bleeding at an incidence rate 4.9 per 100 person-years compared with just 2.9 per 100 person-years for the European labeling recommendation of apixaban 2.5 mg.
There was no difference between apixaban 5 mg and 2.5 mg groups in the risk of stroke/systemic embolism or death.
The authors concluded:
Compared with 2.5 mg, use of 5 mg apixaban was associated with a higher risk of bleeding in patients with atrial fibrillation and severe chronic kidney disease, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing recommendations on the basis of kidney function by the European Medicines Agency, which differ from those issued by the US Food and Drug Administration.
As the recommendations in the US labeling are based only on PK/PD studies and not direct outcomes, this data may eventually result in an adjustment to the US labeling for apixaban dosing for patients with severe renal impairment.
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