Over the last decade there has been a shift in the prescription of oral anticoagulants, with NOACs now by far the most preferred anticoagulants [
16‐
18]. Evaluating the prescription policy within our hospital over several years revealed important learning points to optimise prescribing but also monitoring of stroke prevention after initiation. Of all 3,231 AF patients who started on an NOAC, 10.7% received an inappropriate dose and the appropriateness of the prescription could not be determined in 14.1%. All incorrect prescriptions were actionable, meaning that the prescription had to be corrected to optimise stroke prevention, with 5.4% of the prescriptions requiring a higher dose and 4.5% of all prescriptions requiring a lower dose. The remaining actionable 0.8% were prescriptions for doses not registered for stroke prevention, dabigatran 75 mg and rivaroxaban 10 mg, and would also require a dose increase. The error rate is fairly low compared with rates found in other studies, possibly because most patients with AF are seen at our specialised AF nurse-led clinic providing integrated chronic care supervised by a cardiologist [
19]. Nurse-led structured care of patients with AF has been associated with significantly improved guideline adherence [
20]. Another study demonstrated that patient outcomes (cardiovascular-related hospitalisations and death) with nurse-led care were at least as good as in clinical trials [
21]. Good outcomes in nurse-led care could very well be due to higher guideline-adherent antithrombotic treatment [
22]. The percentage of patients with reduced renal function was relatively low with <10% of the patients having a renal function (eGFR) <50 ml/min. This could indicate that patients with impaired renal function are still typically prescribed a vitamin K antagonist. A reduced dose NOAC was a significant predictor for an incorrect prescription and percentage-wise this was the highest for apixaban 2.5 mg. The same pattern in prescription errors was seen in previous studies [
23‐
26]. In our study, the prescription of a reduced dose was underdosed in 10.4–41.4% of the reduced dose prescriptions. Patients who were prescribed an NOAC in a reduced dose had an OR of 2.97 for receiving an incorrect prescription. This could indicate that prescribers are hesitant to prescribe the full NOAC dose. The use of a reduced dose NOAC without the presence of any dose-reduction criteria could lead to a sub-optimal reduction of the stroke risk, although this has not been studied extensively [
13,
27]. Noteworthy, a study in Korean AF patients demonstrated that guideline-discordant dabigatran 110 mg (
n = 183) had a similar efficacy and safety compared with dabigatran 150 mg (
n = 294) [
28]. The effect of age on receiving an incorrect dose in apixaban and dabigatran prescriptions also illustrates that physicians tend to choose the low dose. The finding that patients aged ≥80 years had lower odds of receiving an inappropriate dose reduction compared with younger patients confirms this hypothesis. This result was mainly driven by the large proportion of dabigatran prescriptions. Age is not a single criterion for apixaban dose reduction and was found to be indicative for an incorrect dose. The high OR for age in incorrect apixaban prescriptions shows that age is often used as a single criterion for dose reduction in apixaban while this is only true in the presence of a low body weight or renal dysfunction (2 out of 3 criteria). Because age is a single dose reduction criterion for dabigatran, a low OR for incorrect prescriptions was found for advanced age. A high bleeding risk, HAS-BLED score ≥3, was not identified as a significant predictor for incorrect apixaban or dabigatran prescription. The ESC explicitly mentions that the bleeding risk should be evaluated; however, a high bleeding risk should not be a reason to withhold oral anticoagulation [
14]. With the prescription of NOACs shifting more towards primary care, there will be a transition period in which more attention has to be paid to the prescribing and monitoring. The same tailor-made monitoring tools within a hospital can also be used in primary care.
Recommendations for improving prescribing
The key to correct prescribing of NOACs in AF patients is the full availability of patient information and the incorporation of all these patient-specific characteristics into the decision making. Ideally, the NOAC can only be prescribed if all necessary information is available. The physician should at least have information on age, weight, comorbidities, renal function (serum creatinine) and concomitant medication. The pharmacist responsible for checking the medication should also have full access to this information, which is required for them to check the prescription before dispensing. Preferably, the patient’s medical history and comorbidities should be registered in the electronic system in such a way that these factors can be computerised into categorical variables and used to monitor the appropriateness of the NOAC dose at a population level. One of the variables most commonly unavailable was renal function, although this is an important factor for determining the correct dose and also for determining a possible contraindication. The renal function can decrease rapidly, especially in older patients, hence periodic monitoring is important to determine if dose adjustment is necessary. Guideline adherence to treatment initiation can still be improved and is a good starting point to decrease the extent of undertreatment and overtreatment [
29].
All physicians who prescribe NOACs should be aware of the most common prescription mistakes reported in the present study, namely: 1) inappropriate dose reduction in apixaban patients, especially in those >80 years; 2) inappropriate full-dose dabigatran in patients with using either verapamil or with an impaired renal function. A pharmacist could also assist in the prescription process to further reduce drug-related problems [
30]. With the experience of several years of NOAC prescribing, more attention now needs to be paid to achieving and maintaining optimal stroke prevention in the future.