135 CLINICAL CONSEQUENCES OF OFF-LABEL REDUCED DOSING OF NOACS IN AF What is already known on this topic · Postmarketing studies reported that many patients with atrial fibrillation receive a reduced dose of non-vitamin K antagonist oral anticoagulants (NOACs) without a clear indication. · To what extent patients experience clinical consequences of such off-label reduced dosing (OLRD) is not yet known. What this study adds · While other studies have compared patients with OLRD to patients with on-label dosing (i.e. both on-label reduced and on-label non-reduced), we compared OLRD to on-label non-reduced dosing (OLNRD), which is clinically the most relevant comparison. · Our systematic review and meta-analysis showed that there is no statistically significant increased risk of stroke/thromboembolism, nor a decreased bleeding risk, nor a difference in risk of all-cause mortality in patients with OLRD of NOACs compared with OLNRD of NOACs. How this study might affect research, practice or policy · This study summarises all observational studies on the clinical outcomes of OLRD of NOACs, thereby informing clinicians that they, in close discussion with their patients, should decide on the best treatment regimen in the specific situation of each patient. INTRODUCTION Oral anticoagulants are of critical value for stroke prevention in atrial fibrillation (AF). Despite the effectiveness of the oldest form of anticoagulation, vitamin K antagonists (VKA), studies have repeatedly shown that historically patients with AF often do not receive anticoagulants or antiplatelet therapy. Such ‘underuse’ of anticoagulants in patients with AF at high risk of stroke was in the order of 50%.1 With the introduction of non-VKA oral anticoagulants (NOAC) in 2009, underuse of anticoagulants for AF decreased considerably given that randomised trials showed that NOACs are at least as effective as VKAs, have fewer drug and food interactions, and overall a lower risk of serious bleeding, notably intracranial bleeds.2 Moreover, NOACs do not require INR monitoring: a fixed dose can be used.3 Currently, four NOACs have been approved for patients with AF,4–8 and these agents rapidly became recommended as first-line agents for most AF patients in clinical guidelines. While this initially alleviated the concerns about underuse of anticoagulants, a new pitfall has arisen. For each NOAC, besides a non-reduced dose, a reduced dose is available for specified subgroups of 8
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