Abstract
Direct oral anticoagulants (DOACs) have been demonstrated to be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF). This meta-analysis aims to assess the effect of DOACS vs. VKA in patients ≥ 80 and AF. Primary endpoints were stroke or systemic embolism and all-cause death. Secondary endpoints included major bleeding, intracranial bleeding, and gastrointestinal bleeding. A random-effects model was selected due to significant heterogeneity. A total of 147,067 patients from 16 studies were included, 71,913 (48.90%) treated with DOACs and 75,154 with VKA (51.10%). The stroke rate was significantly lower in DOACs group compared with warfarin group (Relative risk (RR): 0.72; 95% confidence interval (CI): 0.63–0.82; p < 0.001). All-cause mortality was significantly lower in DOACs group compared with warfarin group (RR: 0.82; 95% CI: 0.70–0.96; p = 0.012). Compared to warfarin, DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) or gastrointestinal bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p = 0.678) but a 43% reduction of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) was observed. Our meta-analysis demonstrates that DOACs are effective and safe with statistical superiority when compared with warfarin in octogenarians with AF.
Highlights
The incidence of nonvalvular atrial fibrillation (AF) increases exponentially with age [1,2], and its prevalence varies from 0.1% among patients younger than 55 years to 9–17.7% in those aged 80 years or older [2,3,4,5,6]
The stroke rate was significantly lower in Direct oral anticoagulants (DOACs) group compared with warfarin group [Relative risk (RR): 0.72; 95% confidence interval (CI): 0.61–0.84; p < 0.001] (Figure 2)
DOACs were not associated with reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p = 0.108) (Figure 4) but reduced the risk of intracranial bleeding (RR: 0.47, IC 95% 0.36–0.60; p < 0.001) (Figure 5)
Summary
The incidence of nonvalvular atrial fibrillation (AF) increases exponentially with age [1,2], and its prevalence varies from 0.1% among patients younger than 55 years to 9–17.7% in those aged 80 years or older [2,3,4,5,6]. Octogenarians are growing faster than those above age 65, and the global population aged 80 years and over is projected to triple in 2050 [7]. DOACs overcome the limitations of VKA, showing fewer drug and dietary interactions and rapid onset of action. Based on these advantages over VKA, DOACs have been recommended as the first-choice therapy to prevent stroke in AF [15,16,17]. The potential benefits of DOACs have not been studied in octogenarians with AF because the elderly population was underrepresented in the pivotal randomized controlled trials (RCTs), which excluded these high-risk patients. The rate of patients aged ≥80 and ≥85 years in the pivotal RCTs was 13–17% and 4–7%, respectively [18,19,20,21,22,23]
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