Underdosing of Direct Oral Anticoagulants\u3000- Pros or Cons?

Abstract

and other drugs, thereby making it difficult to maintain optimal therapeutic intensity. DOACs were expected to reduce under-/overdosing, because they are prescribed at a fixed dose and do not require routine or frequent laboratory monitoring. Optimal doses of each DOAC are determined according to age, renal function, and body weight, and the efficacy of these doses has been confirmed by the large-scale randomized clinical trials (RCT). However, inappropriate dosing of DOAC-treated patients is commonly seen in current daily clinical practice. ORBIT-AF II, a large-scale observational study of AF patients in the USA, showed that 9.7% of DOAC-treated patients were underdosed, and 3.4% were overdosed.3 The Fushimi AF Registry, a cohort study of AF patients in Japan, also showed that nearly half of patients receiving low-dose regimens of DOAC were off-label underdosed.4 The main problem of prescribing an inappropriate dose of DOAC is that it may be associated with poor outcomes. In ORBIT-AF II, overdosing was associated with increased all-cause death compared with recommended doses (adjusted hazard ratio: 1.91; 95% confidence interval [CI]: 1.02–3.60), and underdosing was A trial fibrillation (AF) is a cardiovascular disorder that continues to increase in incidence in the 21st century. In patients with AF, stroke is one of the most serious complications, which leads to substantial morbidity and mortality. Thus, stroke prevention is the cornerstone in managing patients with AF1 and anticoagulation is the most effective treatment to prevent stroke. However, the risk of bleeding is a drawback of this therapy, and it is important to strike a balance between the thromboembolic and bleeding risks. In this issue of the Journal, Murata et al demonstrate the effectiveness and safety of off-label underdosing of direct oral anticoagulants (DOAC) using data from the SAKURA AF Registry, a prospective multicenter observational registry in Japan.2 They report that approximately 26% of DOAC users received an inappropriate dose of DOAC (4% over-dose and 22% underdose); net clinical events were higher in the overdosed DOAC group, whereas they were equivalent (or might be better because of the decrease in major bleeding events) in the underdosed group. Inappropriate dosing of anticoagulant drugs has been a problem in real-world clinical practice. With regard to warfarin, underor overdosing was common because of the narrow therapeutic range and interactions with food Article p 727