Appropriateness of the Direct Oral Anticoagulants Dosing in the Middle East Gulf Region

Abstract

Direct oral anticoagulants (DOACs) have proven efficacy to prevent cardioembolic strokes. Data are scarce about the appropriateness of DOAC dosing in the Middle East. We investigated the prevalence of inappropriate DOAC dosing in the region. A cross-sectional study was conducted at our hospital between April 2015 and February 2019 of patients receiving 1 of the 3 available DOACs. Patients with incomplete data sets, those prescribed DOACs for indications other than atrial fibrillation, on DOACs for <30 days, and dialysis patients were excluded. A total of 608 met the inclusion criteria. The mean age was 65.2 ± 13.9 years, and most were men (58.6%). The mean CHA2DS2-VASc score was 3.8 ± 2.0. There were 346 (56.9%) on apixaban, 123 (20.2%) on dabigatran, and 139 (22.9%) on rivaroxaban. The logistic regression model showed that for the 3 agents together, age, eGFR, major bleeding history, and history of prior stroke were significantly associated with the decision to inappropriately underdose (P < 0.05). Fifteen patients had an ischemic stroke after apixaban initiation (5 underdosed and 3 overdosed). Among patients with at least one follow-up encounter, major bleeding occurred in 13 patients (11.7%) with inappropriate dosing compared with 29 patients (6.0%) with appropriate dosing (P = 0.04). Ischemic stroke occurred in 11 patients (9.9%) with inappropriate dosing compared with 15 patients (3.1%) with appropriate dosing (P < 0.01). We concluded that inappropriate DOAC underdosing is common in our region, particularly with apixaban and rivaroxaban. It is associated with increased risk of stroke and bleeding. More education targeting prescribers is needed to encourage adherence to standard dosing criteria.

Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis

“…A history of minor bleed (HAS-BLED <3 vs HAS-BLED ≥3) was associated with an increased risk of underdosing 8 9 14 22 27 30–39. Similarly, an increased risk of underdosing was observed with age ≥65 years and age ≥75 years (reference category: ≤65 years) 8 9 14 22 27 30–39.…”

“…Fifteen studies conducted regression analyses on the drivers of inappropriate NOAC dosing, examining patient demographics (age, sex and weight), comorbidities (diabetes (type unspecified), hypertension and congestive heart failure), stroke risk factors (history of prior stroke, CHA 2 DS 2 -VASc score and CHADS 2 score), renal function (CrCl and estimated glomerular filtration rate (eGFR) and bleeding risk (HAS-BLED and history of minor bleed) 8 9 14 22 27 30–39…”

Prevalence, risk factors, and prediction of inappropriate use of non-vitamin K antagonist oral anticoagulants in elderly Chinese patients with atrial fibrillation: A study protocol

“…In particular, NOAC over-dosing was associated with increased all-cause mortality, while NOAC under-dosing was associated with higher rates of hospitalization for cardiovascular conditions ( 27 ). Another study demonstrated that inappropriate NOAC prescriptions were more likely to occur in the older adult population ( 28 ). This is the most worrisome finding because the risk of stroke increases significantly with age.…”

Real-World Effectiveness and Safety of Apixaban versus Warfarin in Patients with Acute Venous Thromboembolism: Experience of a Large Tertiary Hospital in Saudi Arabia

“…In addition to better safety outcomes with apixaban than warfarin, other factors should be considered before selection of anticoagulation agents, including drug–drug interactions, cost, and applicability of routine INR checks. In addition, apixaban dosing should follow the FDA recommendations, considering that Anouassi et al 21 reported subtherapeutic dosing among prescribers practicing in the Gulf region. In our study, apixaban was dosed according to FDA recommendations for treatment of VTE, which could explain the lower rates of VTE recurrence.…”