The Importance of Appropriate Dosing of Nonvitamin K Antagonist Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation

Abstract

Preventing thromboembolic events, while minimizing bleeding risks, remains challenging when managing patients with atrial fibrillation (AF). Several factors contribute to current dosing patterns of nonvitamin K antagonist oral anticoagulants (NOACs), including patient characteristics, comorbidities, and physician judgment. Application of NOAC doses inconsistent with the drug labels may cause patients to receive either subtherapeutic (increasing stroke risk) or supratherapeutic (increasing bleeding risk) anticoagulant levels. In clinical practice, under- or over-dosing of NOACs in patients with AF is not uncommon. This analysis of prospective and retrospective registry and database studies on NOAC use in patients with AF (with at least 250 patients in each treatment arm) showed that under-dosing may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose. This may reflect underlying conditions and patient factors that increase bleeding despite NOAC dose reduction. Such factors could drive the observed overuse of reduced NOAC dosages, often making the prescription of reduced-dose NOAC an intentional label deviation. In contrast, over-dosing more likely occurs accidentally; instead of providing benefits, it may be associated with worse safety outcomes than the standard dose, including increased bleeding risk and higher all-cause mortality rates. This review summarizes the main findings on NOAC doses usually prescribed to patients with AF in clinical practice.

Effectiveness and Safety of Reduced and Standard Daily Doses of Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: A Cohort Study Using National Database Representing the Japanese Population

“…Our findings differed from those in studies from the United States (US), 14–16 Europe, 17–21 Israel, 22 and Asia 23–28 reporting the association between reduced-dose DOACs and the increased risk of S/SE. Some systematic reviews have also reported that use of reduced-dose DOACs produced less favorable outcomes than standard-dose DOACs.…”

“…Some systematic reviews have also reported that use of reduced-dose DOACs produced less favorable outcomes than standard-dose DOACs. 17 , 29–32 However, several reports, mainly from Asia 33–46 but also from the US 47–50 and Israel, 51 as well as international/global studies, 52 , 53 show that reduced-dose DOACs were not associated with an increased risk of S/SE; in some of these studies, investigators specified reduced-dose as “inappropriately reduced-dose” or “off-label underdose”. 39 , 47–49 , 51 , 53 In a recent systematic review, Choi et al reported that reduced-dose DOACs were not associated with an increased risk of S/SE in Asians, 54 and Shen et al reported the same conclusion in a systematic review that included a diverse population.…”

Appropriateness of Non-vitamin K Antagonist Oral Anticoagulants Dosing According to Different Prescription Guides Used in Belgian Ambulatory Care

“…One is that physicians correctly take more clinical factors into consideration and hence, both the SmPC and EHRA PG still fall short of guide clinical practice. However, prior retrospective and observational data have clearly shown that dosing that deviates from recommendations is associated with increased risk of adverse events and even mortality [ 7 , 27 ]. Therefore, the second explanation is that physicians still are falling short of making correct dosing decisions, which calls for more physician education to improve patient outcomes.…”

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

“…Doctors must not choose lower dose of NOACs just out of a fear of bleeding (thus ignoring the risk of stroke) [74]. Under-dosing of NOACs in patients with AF may be associated with reduced effectiveness for stroke prevention, with similar or even increased bleeding than with the standard dose [81]. Anticoagulation monitoring enables personalized and…”