Off-label use of reduced dose direct oral factor Xa-inhibitors in subjects with atrial fibrillation: a review of clinical evidence

In real-world clinical practice, underdosing, i.e. off-label use of reduced doses (RD), of oral factor Xa inhibitors (oFXaIs) is quite common in stroke prevention in nonvalvular atrial fibrillation, possibly reflecting the hope to increase safety without reducing efficacy in selected patients. To assess whether this strategy is associated with some clinical benefit, we used a physician-centered approach to evaluate whether current evidence supports the hypothesis that a substantial proportion of underdosing may be voluntary rather than casual, whether and to what extent oFXaIs’ dose rather than patients’ characteristics are associated with bleeding events, and which are the safety and efficacy clinical implications of oFXaIs’ underdosing. Our review found consistent evidence that underdosing is often an intentional strategy; however, available studies do not demonstrate a sizeable net clinical benefit of using off-label RD oFXaIs.