Research LettersValidity of different dose reduction criteria for apixaban
Section snippets
Background
Oral anticoagulation is the cornerstone of managing thromboembolic risk in atrial fibrillation (AF). The non-vitamin K oral anticoagulants (NOACs) are as effective at reducing thromboembolic events as warfarin, with lower bleeding risk, and without need for coagulation monitoring. However, NOACs exhibit varying degrees of renal excretion and require dose adjustment in moderate to severe renal impairment to avoid excess anticoagulation and bleeding. The pivotal clinical trials of NOACs assessed
Methods
BC Renal is a provincial government organization that funds, coordinates, and monitors patients with CKD in British Columbia (defined by eGFR <60ml/min/1.73 m2, or structural abnormalities on imaging or kidney biopsy), a Canadian province of 5.1 million people. Registration is mandatory for funding of CKD medications, access to multidisciplinary care teams, and renal replacement therapy. Laboratory data recorded in the BC Renal health information system are auto-loaded via interfaces with both
Results
Among 18,209 non-dialysis CKD patients, 1064 had a diagnosis of AF. After exclusions, the final study cohort included 831 patients as previously published.3 Of note, 95 (11.4%) patients weighed ≤60kg. Applying the ARISTOTLE trial criteria identified 362 patients who should receive dose reduced apixaban.
Applying 1 of 2 criteria (either age or creatinine) to identify who should receive reduced-dose apixaban correctly classifies 458 (55.1%) patients (Figure 1 upper left panel, Online Table 1). 373
Discussion
We found using both creatinine and age (2 of 2 criteria) correctly classified apixaban dose requirements in 93.6% of patients with AF, with only 6.4% of patients misclassified as needing standard dose when actually requiring reduced-dose by trial criteria (overdosing). Substituting eGFR for creatinine increased this misclassification from 6.4% to 14.6%. On the other hand, using either creatinine or age (1 of 2 criteria) or creatinine alone misclassified 39.1% to 44.9% of patients for dose
Limitations
The provincial renal database over represents renal impairment compared to an unselected population with AF. This potentially shifts patients ≥80 years or weight ≤60kg from theoretically not needing dose reduction according to the 2 of 2 criteria to needing dose reduction, which would exaggerate the apparent concordance (Figure 2, shift from red to green segments as indicated by arrows). However, this would not change the conclusion that the 2 of 2 criteria represents the best compromise in
Conclusion
We recommend that observational analyses of apixaban dosing use serum creatinine ≥1.5 mg/dL combined with age ≥80 years to classify patients who require dose reduction in real world practice as this represents the best approximation to the ARISTOTLE trial criteria if weight is unavailable. This should not be used for clinical decision making where the complete trial criteria are recommended. The remaining 3 definitions potentially used by health services researchers misclassify apixaban dose
Funding
The authors received no financial support in preparation of the manuscript.
Conflict of interest
None declared.
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