Abstract
Background: Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk–benefit profile. However, there are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients.Methods: After comprehensively searching Embase, PubMed, and Cochrane databases, five phase III randomized controlled trials involving 28,137 elderly participants were included in this study. The efficacy outcome was stroke or systemic embolism, and the safety outcome was major bleeding. We conducted a network meta-analysis by using a Bayesian random-effect model for the first time to evaluate the efficacy and safety of main DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran) and warfarin in elderly patients with AF. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were used to assess the effect of drugs on efficacy and safety. The rank probabilities were used to reflect the hierarchy of drugs, and a larger rank probability value symbolized a better rank of drugs.Results: In the prophylaxis of stroke or systemic embolism, apixaban was found to be the best among DOACs compared to warfarin (HR, 0.71; 95% CI: 0.33–1.50), though this finding was not statistically significant. Apixaban ranked the best (rank probabilities, 41.2%) in efficacy of drugs, followed by rivaroxaban, edoxaban, dabigatran, and warfarin (rank probabilities, 31.8, 15.9, 10.9, and 0.2%, respectively). In reducing the risk of major bleeding, apixaban was found to be the best among DOACs too, compared to warfarin (HR, 0.64; 95% CI: 0.33–1.30), though this finding was not statistically significant. In safety, apixaban ranked the best (rank probabilities, 71.4%), followed by edoxaban, dabigatran, warfarin, and rivaroxaban (rank probabilities, 21.0, 5.8, 0.9, and 0.8%, respectively).Conclusions: DOACs showed a lower incidence of stroke/systemic embolism and major bleeding compared with warfarin in antithrombotic therapy in elderly patients (aged ≥75 years), with apixaban being the best of those interventions. Therefore, apixaban should be given priority as an anticoagulant in stroke prevention for elderly patients with AF.
Highlights
Atrial fibrillation (AF) is one of the most common cardiovascular diseases worldwide
We searched studies by using keywords that included “Atrial fibrillation” or “AF” or “non-valvular AF” and “elderly patients” or “advanced age” or “older age” and “anticoagulation” or “antithrombotic” or “anticoagulants” or “warfarin” or “dabigatran” or “apixaban” or “rivaroxaban” or “edoxaban.” The electronic search strategies were provided in the online Supplementary S1
In the prophylaxis of stroke or systemic embolism, apixaban was the best among the Direct oral anticoagulants (DOACs) compared to warfarin (HR, 0.71; 95% confidence intervals (CIs): 0.33–1.50), though this result was not statistically significant
Summary
Atrial fibrillation (AF) is one of the most common cardiovascular diseases worldwide. AF is associated with an increased risk of stroke and increases the risk of heart failure and allcause mortality [2]. The prevalence of AF increases with age, and two-thirds of patients with AF are the elderly (aged ≥75 years) [6]. Older age is a known factor that can increase the risk of stroke/systemic embolism, which is one of the most common complications of AF; the occurrence of comorbidities is frequent in the elderly [6]. Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk–benefit profile. There are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients
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