Clinical characteristics of patients with direct oral anticoagulant (DOAC) levels outside expected ranges: A retrospective chart study

Background: Routine monitoring direct oral anticoagulants (DOAC) is not recommended, yet DOAC levels are frequently measured in clinical practice. Interpretation of levels, especially those outside expected ranges, is challenging. Until now it's unclear which patients are at risk for these levels. Aim: Identify clinical characteristics of patients with DOAC levels outside expected ranges. Methods: Patients of 2 Dutch academic medical centers with a DOAC concentration measured between 2012 and 2019 were included. DOAC levels above upper limit peak and below lower limit trough ranges, based on DOAC registration trials, were assigned outside expected range. Differences between patients were evaluated using Chi-square, independent sample-T tests and multivariable logistic regression analysis. Results: Of 597 patients with DOAC measurement, 108 (18.1%) had levels outside expected ranges. Compared to patients with levels within range, patients with levels above range (n = 64) were older (71.1 vs. 60.6 years), more often had creatinine clearance <50 ml/min (32.8% vs. 13.9%). and used more often interacting (17.2% vs. 6.7%) and/or antiplatelet co-medication (25.0% vs. 13.1%). Patients with levels above (62.5%) and below range (61.4%) more often had atrial fibrillation as DOAC indication versus patients with levels within range (39.1%). Age (OR 1.046 [1.025–1.068]) was associated with levels above range, while dabigatran versus apixaban was associated with levels below range (OR 6.060 [1.836–19.996]). Conclusion: Particularly older aged patients with additional comorbidity and co-medication had DOAC levels outside expected ranges. Prospective studies are essential to investigate whether identification of patients with levels outside expected ranges is necessary to reduce the risk of clinically relevant adverse events.