Safety and efficacy of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: systematic review and meta-analysis of 22 studies and 440 281 patients

Aims: The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population.

Methods and results: MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70-0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85-1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38-0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48-0.79) and fatal bleeding (HR 0.46; 95% CI 0.30-0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30-1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39-2.08) and edoxaban (HR 1.37; 95% CI 1.14-1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18-1.85).

Conclusion: In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.