Meta-Analysis of Direct-Acting Oral Anticoagulants Compared With Warfarin in Patients >75 Years of Age

https://doi.org/10.1016/j.amjcard.2019.02.060Get rights and content

Older patients with atrial fibrillation (AF) are at higher risk of thromboembolic events and oral anticoagulant (OAC)-related bleeding complications. This meta-analysis evaluates the efficacy and safety of direct-acting OACs (DOACs) compared with warfarin in older patients with nonvalvular AF. PubMed, Embase, and Cochrane Central databases were searched for randomized controlled trials assessing the efficacy and safety of DOACs compared with warfarin in AF patients who were >75 years old. Treatment effects and relevant standard errors were calculated from the available data. These values were imputed in software R to perform meta-analysis through generic inverse variance method. Additionally, we performed a network meta-analysis to compare the relative efficacy and safety of each OAC. Five substudies of randomized controlled trials, comprising 28,135 older participants, were included in the analysis. DOACs as a group were found to have superior efficacy compared with warfarin in reducing stroke or systemic embolization (hazard ratio 0.76, 95% confidence intervals 0.67 to 0.86, p <0.01). The rate of major bleeding was similar, but intracranial hemorrhage was significantly lower in patients randomized to a DOAC (hazard ratio 0.48, 95% confidence intervals 0.34 to 0.67, p <0.01). Apixaban was the only DOAC that significantly reduced all 3 outcomes of systemic embolization, major bleeding, and intracranial hemorrhage compared with warfarin (by 29%, 36%, and 66%, respectively). In conclusion, DOACs were found to be safer and more effective than warfarin for the treatment of nonvalvular AF in older patients. Apixaban appears to provide the best combination of efficacy and safety in this population.

Section snippets

Methods

A literature search was performed in PubMed, Embase, and Cochrane Central through December 12, 2018. The keywords utilized were “nonvitamin K antagonist oral anticoagulants” or “direct oral anticoagulants” or “dabigatran” or “rivaroxaban” or “apixaban” or “edoxaban” AND “stroke” or “systemic embolism” or “major bleeding” or “intracranial hemorrhage,” with the limits for humans and RCTs activated. No restriction for language or publication year was used. The studies were electronically and

Results

Our initial search yielded 1,409 articles. After electronic deduplication, 1,113 studies remained. A further title and the abstract review led to the exclusion of the least relevant articles, and 13 articles were selected for the final full-text review (Figure 1). On full-text review, 5 RCTs, including 27,639 older patients with nonvalvular AF randomized to a DOAC or warfarin, were selected for meta-analysis.9, 10, 11, 12, 13 Table 1 shows the baseline characteristics in the trials.

Figure 2

Discussion

In this comprehensive meta-analysis of data from RCTs evaluating the safety and efficacy of DOACs compared with warfarin, we report novel and important findings in the subgroup of older AF patients. First, DOACs as a class were superior to warfarin with respect to both efficacy and safety; second, individual DOACs demonstrated similar efficacy to each other in the prevention of SSE; third, apixaban was associated with the lowest risk of major bleeding; fourth, apixaban, edoxaban, and dabigatran

Disclosures

None of the authors have any conflicts of interest or funding sources to disclose.

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