Abstract
Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients. Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months. Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile. Results Of 100 enrolled patients, 82 came for a second visit, 55 of whom were treated with apixaban 5-mg BID. Seven (63.6%, 95% confidence interval [CI]: 35.4–84.8%) and nine (81.8%, 95% CI: 52.3–94.9%) of 11 patients with a baseline trough and peak level in the upper quintile, respectively, had a subsequent level that remained within this range. Only one (9.1%, 95% CI: 1.6–37.7%) patient had a subsequent level that fell just lower than the median. Conclusion The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months. Accordingly, the finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg BID dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis.
Highlights
Direct-acting oral anticoagulants (DOACs) have revolutionized oral anticoagulant therapy because they were shown to be safe and effective without the need for routine monitoring of their anticoagulant activity.[1]
The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months
The finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg twice daily (BID) dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis
Summary
Direct-acting oral anticoagulants (DOACs) have revolutionized oral anticoagulant therapy because they were shown to be safe and effective without the need for routine monitoring of their anticoagulant activity.[1]. In the randomized trials that led to its approval, apixaban was given in a standard dose of 5-mg twice daily (BID) in most patients and in a reduced dose of 2.5-mg BID in patients who met at least two of three “ABC” criteria (age !80 years, body weight 60 kg, and serum creatinine !133 μmol/L).[3,5] 2.5-mg BID is recommended for patients who meet these criteria.[4,6,7] Despite these recommendations, in daily practice approximately 50% of patients are treated with the 2.5-mg dose without meeting the labeled criteria for dose reduction (i.e., “off-label” dose reduction),[8,9] presumably because treating physicians are concerned with the risk of bleeding. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients
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