This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and
stroke prevention in
atrial fibrillation with the new direct oral
anticoagulants (NOACs): 1. In patients prescribed a
NOAC, can the
anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut-off points" between which anticoagulation is therapeutic (i.e. the "therapeutic range") be defined? 2. In patients who are taking a
NOAC and
bleeding (e.g. intracerebral haemorrhage), can the
anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can
NOAC-associated
bleeding and complications be minimised and patient outcome improved? 3. In patients taking a
NOAC who experience an acute
ischaemic stroke, to what degree of anticoagulation or plasma concentration of
NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic
ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a
NOAC (or
warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a
NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have
atrial fibrillation and are at high risk of
stroke but also
bleeding)? 7. Can dose-adjusted
NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored
NOAC therapy? 8. Is there a dose or dosing regimen for each
NOAC that is as effective and safe as adjusted-dose
warfarin for patients with
atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?