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

• Published in: European heart journal. Cardiovascular pharmacotherapy Vol. 7; no. 4; pp. 334 - 345
• Main Authors: Bo, Mario, Corsini, Alberto, Brunetti, Enrico, Isaia, Gianluca, Gibello, Maddalena, Ferri, Nicola, Poli, Daniela, Marchionni, Niccolò, De Ferrari, Gaetano Maria
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 23.07.2021
• Subjects: Administration, Oral; Anticoagulants; Atrial Fibrillation - complications; Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Cardiac arrhythmia; Drug dosages; Factor Xa Inhibitors; Humans; Off-Label Use; Stroke; Stroke - diagnosis; Stroke - etiology; Stroke - prevention & control; Direct oral anticoagulants; Oral anticoagulant therapy; Off-label dosing; Non-valvular atrial fibrillation; Reduced doses; Underdosing
• ISSN: 2055-6837; 2055-6845; 2055-6845
• DOI: 10.1093/ehjcvp/pvaa103

Abstract In real-world clinical practice, underdosing, i.e. off-label use of reduced doses (RDs), of oral factor Xa inhibitors (oFXaIs) is quite common in stroke prevention in non-valvular 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-centred 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.