Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

Abstract

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.

Non‐vitamin K antagonist oral anticoagulant (NOAC) use and dosing in Canadian practice: Insights from the optimising pharmacotherapy in the management approach to lowering risk in atrial fibrillation (OPTIMAL AF) Programme

“…7 Use of a reduced-dose NOAC which is discordant with product labelling is associated with increased cardiovascular hospitalisation while not using a reduced dose in those who qualify is associated with increased allcause mortality and risk for bleeding. 2,6 Consistent with previous reports, [2][3][4]6,8,9 the proportion of patients apparently "underdosed" was higher than the proportion "overdosed." Clinicians may lean towards use of a reduced dose of NOAC in patients where some, but perhaps not all of the reduced-dose criteria are met.…”

“…6 Further, NOAC "overdosing" was associated with increased all-cause mortality and bleeding while "underdosing" was associated with increased cardiovascular hospitalisation and risk of stroke. 6 Clinical reasons for prescribing the reduced dose, particularly in cases where criteria for use of the reduced dose was not met, have not been fully explored.…”

“…In Canadian registries, there appears to be a 7%‐16% incidence of reduced‐dose NOAC use not consistent with Health Canada product labelling 3‐5 . A systematic review of 75 observational studies showed that, while most patients treated with NOACs for stroke prevention in AF received doses in accordance with guidelines, as many as 25%‐50% received “off‐label” doses 6 . Further, NOAC “overdosing” was associated with increased all‐cause mortality and bleeding while “underdosing” was associated with increased cardiovascular hospitalisation and risk of stroke 6 .…”

“…A systematic review of 75 observational studies showed that, while most patients treated with NOACs for stroke prevention in AF received doses in accordance with guidelines, as many as 25%‐50% received “off‐label” doses 6 . Further, NOAC “overdosing” was associated with increased all‐cause mortality and bleeding while “underdosing” was associated with increased cardiovascular hospitalisation and risk of stroke 6 . Clinical reasons for prescribing the reduced dose, particularly in cases where criteria for use of the reduced dose was not met, have not been fully explored.…”

Response to “Direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease”

“…Of those who received inappropriate dosing, the majority were underdosed rather than overdosed, consistent with findings from other real-world studies and registries. 1 This would be expected to potentially reduce efficacy and bleeding rates, although neither finding was apparent in our cohort of patients with moderate to severe renal insufficiency. We believe that further studies will be essential to help guide the treatment of this underrepresented group of patients.…”