Do off-label DOAC doses increase the risk of adverse clinical outcomes in patients with atrial fibrillation?
Off-label DOAC dosing in atrial fibrillation is common (25-50% in most studies) and is associated with increased risks of mortality, bleeding, stroke, and cardiovascular hospitalization compared to guideline-directed dosing.
AIMS: Worldwide observational studies are evidencing discordance between guidelines and real-world practice regarding direct oral anticoagulant drug (DOAC) doses. This systematic review summarizes and evaluate DOACs use in real-world practice. METHODS: This review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines searching PubMed (MEDLINE) and Medscape databases. RESULTS: Data from 75 studies showed that most of the patients treated with DOACs for stroke prevention in atrial fibrillation received doses in accordance to the guidelines. However, a significant number of patients received off-label doses (25-50% in most of the studies evaluated). DOAC overdosing was associated with increased all-cause mortality and worse bleeding events while underdosing was associated with increased cardiovascular hospitalization and, particularly for apixaban, with a nearly 5-fold increased risk of stroke. CONCLUSION: Patients prescribed with off-label DOAC doses did not receive the full benefit of anticoagulation and presented an increased risk of stroke, bleeding and/or adverse effects.
Santos et al. (Mon,) studied this question.