Usual On-therapy Ranges of Drug Concentrations in Patients with Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

Background:  Although most patients with atrial fibrillation (AF) receiving a direct oral anticoagulant (DOAC) do not require drug concentration measurements, there are situations where such information could be useful. Existing guidance documents provide usual on-therapy ranges for drug concentrations, but these have important limitations.

Methods:  This is a systematic review and meta-analysis of studies reporting trough and peak levels of DOAC regimens approved for stroke prevention in AF. We used random effects models and the quantile estimation method to estimate the median and a usual on-therapy range (10^th and 90^th percentiles).

Results:  Of 4,822 unique publications, 53 studies met eligibility (29,266 trough and 12,103 peak levels). Usual on-therapy ranges for trough levels were 38 to 155 and 58 to 206 ng/mL for apixaban 2.5 and 5 mg twice daily; 35 to 138 and 33 to 151 ng/mL for dabigatran 110 and 150 mg twice daily; 8 to 54 and 13 to 66 ng/mL for edoxaban 30 and 60 mg daily; and 16 to 74 and 19 to 72 ng/mL for rivaroxaban 15 and 20 mg daily. The corresponding range for peak levels were 96 to 251 and 132 to 343; 65 to 223 and 76 to 285; 57 to 219 and 127 to 407; 131 to 384, and 169 to 313 ng/mL, respectively.

Conclusion:  This systematic review and meta-analysis provides updated and more representative usual on-therapy ranges of DOAC levels in patients with AF.