Determinants for under‐ and overdosing of direct oral anticoagulants and physicians' implementation of clinical pharmacists' recommendations

Abstract

To analyse the appropriateness of direct oral anticoagulant (DOAC) dosing and determinants for under-and overdosing as well as acceptance and implementation rates of pharmacists' interventions. Methods: Cross-sectional study in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs in 2019 (n = 1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists' recommendations and determination of reasons for nonacceptance/nonimplementation. Results: Inappropriate prescribing was observed in 16.9% of patients (n = 286) with underdosing (9.7%) being more prevalent than overdosing (6.9%). For all DOACs considered together, body weight<60 kg (odds ratio [OR] 0.46 [0.27-0.77]), edoxaban use (OR 0.42 [0.24-0.74]), undergoing surgery (OR 0.57 [0.37-0.87]) and being DOAC naïve (OR 0.45 [0.29-0.71]) were associated with significantly lower odds of underdosing. Bleeding history (OR 1.86 [1.24-2.80]) and narcotic use (OR 1.67[1.13-2.46]) were associated with significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment ) and body weight<60 kg ), whereas dabigatran use (OR 0.24 [0.08-0.71]) and apixaban (OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists' advice in 179 cases (79.2%) consisting of 92 (51.4%) recommendations for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. Conclusion:Inappropriate DOAC prescribing remains common, although there is a slight improvement compared to our study of 2016. Clinical services led by pharmacists help physicians to reduce the number of inadequate prescriptions for high-risk medications such as DOACs.

Improving appropriate use of anticoagulants in hospitalised patients: A pharmacist‐led Check of Medication Appropriateness intervention

“…propriate NOAC therapy of which the acceptance rate ranged from 58.3% to 92.6% (with an overall acceptance rate of 71.3%). In their analyses on pharmacist recommendations for NOAC prescriptions, Perlman et al 13 and Moudallel et al 16 found a similar acceptance of more than 70% and 79.2%, respectively. Most of our recommendations pertained to inappropriate NOAC dosing (68.6%).…”

“…This was also observed in other studies evaluating pharmacist-led interventions for NOAC treatments. [13][14][15][16] The clinical rules on NOAC dosing considered a multitude of decision modifiers, including indication, renal function and age, but also contraindications and clinically relevant drug interactions. These many factors add to the difficulty of selecting the correct dose.…”

“…12 Also, pharmacistled clinical services including reviewing all orders for NOACs can reduce the number of inappropriate prescriptions of these drugs. [13][14][15][16] Such interventions are, however, time and personnel intensive, limiting their efficacy to change hospital-wide prescribing behaviours.…”

“…The S‐team study recently showed that implementation of hospital‐based anticoagulant stewardship programmes had a significant impact on bleeding and thrombotic events and resulted in lower all‐cause mortality 12 . Also, pharmacist‐led clinical services including reviewing all orders for NOACs can reduce the number of inappropriate prescriptions of these drugs 13–16 . Such interventions are, however, time and personnel intensive, limiting their efficacy to change hospital‐wide prescribing behaviours.…”

Expert Recommendations on the Usage of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) from India: Current Perspective and Future Direction

“…Underdosing of NOACs has been observed in several countries [74,[76][77][78][79][80]. Dosing of rivaroxaban (adjusted according to kidney function) may be simpler than that of other NOACs, which is slightly more limited by various factors (creatinine, weight, age, treatment with P-glycoprotein inhibitors).…”