Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry

Aims

We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.

Methods

The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.

Results

At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA₂DS₂-VASc score?≥?1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age?≥?80 years in patients on rivaroxaban OR 2.90, 95% CI 1.05–7.9, P?=?0.04; n?=?29] or apixaban OR 3.24, 95% CI 1.04–10.1, P?=?0.04; n?=?22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age?≥?80 years OR 3.49, 95% CI 1.24–9.84, P?=?0.02; n?=?19]; apixaban under-dosing with body weight?≤?60 kg OR 0.06, 95% CI 0.01–0.47, P?<?0.01; n?=?56], CHA₂DS₂-VASc score OR per point 1.47, 95% CI 1.08–2.00, P?=?0.01], and HAS-BLED score OR per point 1.91, 95% CI 1.28–2.84, P?<?0.01].

Conclusion

At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.

Clinical trial registration

NCT02306824.