Effectiveness and safety of vitamin K antagonists and new anticoagulants in the prevention of thromboembolism in atrial fibrillation in older adults - a systematic review of reviews and the development of recommendations to reduce inappropriate prescribing

Background: Oral anticoagulants are used for stroke prevention in patients with atrial fibrillation, the most common cardiac arrhythmia in older adults. The aim of our study was to identify the evidence on the risks and benefits of anticoagulant use among adults aged ≥65 years with atrial fibrillation and to develop recommendations to reduce inappropriate use with a primary focus on new oral anticoagulants. Methods: Systematic review (SR) with search in six databases (up to 12/2016). We included SRs/meta-analyses (MAs) with participants ≥65 years old with atrial fibrillation treated with oral anticoagulation. Two independent reviewers performed study selection, data extraction and quality appraisal. Recommendations were developed based on the evidence identified following a modified GRADE approach. Results: Thirty-eight SRs/MAs were included, drawing on evidence from 74 individual experimental studies. The mean age ranged from 68.2 to 73 years. Treatments investigated included vitamin K antagonists (VKA), new oral anticoagulants (NOACs), platelet aggregation inhibitors (PAI), placebo and no treatment. Comorbidities were reported in 23 SRs, but none reported on frailty status, cognitive status or polypharmacy. Sixteen SRs based on only 3–8 RCTs and thus conveying a significant overlap of studies evaluated the effectiveness of NOACs compared to warfarin. NOACs demonstrated at least equivalent ability to reduce stroke as VKA and a considerably lower risk (OR 0.37 to RR 0.50) of haemorrhagic stroke/intracranial bleeding. Seven SRs were identified comparing VKA to placebo. These revealed a substantial reduction in risk of stroke and mortality for VKA (RR 0.30–0.46)), outweighing an increased risk of bleeding (RR 1.04–3.63) associated with anticoagulation. Eight SRs evaluated the efficacy of VKA compared to PAI: overall, VKA were associated with a lower risk of stroke (OR 0.51–0.68)) and a comparable risk of major bleeding. Conclusions: Anticoagulation treatment using VKA in older people with atrial fibrillation appears beneficial in comparison to PAI and placebo. New oral anticoagulants appear to reduce haemorrhagic strokes and intracranial bleedings more effectively than VKAs and should be considered especially in patients with low TTR (time in therapeutic range)/labile INR (International Normalized Ratio). However, to determine if these results are applicable to all older people, further studies should provide information on frailty, significant impaired renal function, polypharmacy and cognitive status of the participants. The PRIMA-eDS study was supported by a grant from the European Commission within the 7th Framework Programme (Grant No. 305388–2). The work of YVM was also supported by a grant from the NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre. The publication charge was funded by the University of Witten/Herdecke.