Prescriber compliance to direct oral anticoagulant labels and impact on outcomes in Thailand

Abstract

Aims This study aimed to evaluate the prescriber compliance to the approved labels of direct oral anticoagulants (DOACs) and impact of appropriateness of dosing on clinical outcomes. Methods A retrospective study was conducted using simple‐stratified random sampling of adult patients receiving ≥6 months of DOACs for various indications during 2013–2017 in 10 tertiary care hospitals. Patients were classified into 3 dosing groups including approved dose, underdosing and overdosing based on the Thai Food and Drug Administration‐approved labels. Cox proportional hazard models were used to evaluate the impact of different dosings on thromboembolic and bleeding events. Results From 1200 patients included in the data analysis, prescribing of DOACs was consistent with the approved indications in 1130 cases (94.2%) while 70 patients (5.8%) received DOACs despite having contraindications or with off‐label usage. Among 1026 cases of dosing evaluation cohort, 688 patients (67.1%) received approved doses. There were 227 (21.9%) and 110 (10.7%) cases of underdosing and overdosing, respectively. Multivariate analysis showed that underdosing was associated with an increased risk of thromboembolism 3.023 (95% confidence interval [CI]: 1.291–7.080; P = .011) while overdosing was associated with an increased risk of bleeding requiring hospitalization (adjusted hazard ratio, 3.045; 95% CI, 1.501–6.178; P = .002) and Bleeding Academic Research Consortium type 2 or more (adjusted hazard ratio, 2.196; 95% CI, 1.083–4.452; P = .029). Conclusion Prescribers’ compliance to approved indications were high. However, 1/3 of DOAC prescriptions were inconsistent with approved dosing. Dosing deviation was associated with an increase in adverse clinical outcomes.

Comparison of the HAS‐BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct‐acting oral anticoagulants

“…We used data from the recent study by Wattanaruengchai et al for which the original design and the results of the main study have been published previously 17 . Briefly, the study was a multicentre study conducted in 10 public, tertiary care hospitals from four provinces (Bangkok, Chiang Mai, Nakhon Nayok and Nakhon Ratchasima) in Thailand to evaluate the appropriateness of DOAC use in mixed indications.…”

“…Risk was classified into two levels for low‐ (score 0‐2) and high‐ (score ≥3) risk groups. For the evaluation of DOAC, the labile INR criteria of HAS‐BLED was set to 0 in all patients except those receiving an overdose of DOAC, where it was set to 1, given that inappropriate DOAC overdosing has been shown to increase the risk of bleeding 17 . The ORBIT bleeding risk score comprises five risk factors: age ≥75, anaemia, bleeding history, estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 (calculated by the modification of diet in renal disease equation) and use of antiplatelet drugs 11 .…”

“…For the evaluation of DOAC, the labile INR criteria of HAS-BLED was set to 0 in all patients except those receiving an overdose of DOAC, where it was set to 1, given that inappropriate DOAC overdosing has been shown to increase the risk of bleeding. 17 The ORBIT bleeding risk score comprises five risk factors: age ≥75, anaemia, bleeding history, estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 (calculated by the modification of diet in renal disease equation) and use of antiplatelet drugs. 11 While the risk was originally classified into three levels for low-(score 0-2), intermediate-(score 3), and high-(score ≥4) risk groups, we opted to divide patients into two groups, low versus intermediate/high risk.…”

“…All authors approved the final manuscript. We would like to thank the University Hospital Network, Thailand (UHOSNET) for their contribution in a previous study by Wattanaruengchai et al 17 which made this present study possible.…”

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy

“…Although prescribers may have valid reasons for using off-label DOACs, no studies have yet demonstrated an association between this practice and improved outcomes. Some studies have documented an association between off-label use and increased risk of adverse events, [ 12 , 13 ] but others have not [ 9 , 15 , 16 , 17 ].…”