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Review
. 2025 Jun 9;17(6):e85615.
doi: 10.7759/cureus.85615. eCollection 2025 Jun.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Elderly Patients With Atrial Fibrillation: A Systematic Review

Hafsa Aman  1 , Ayesha Sikandar  2 , Faiza Khawar Dar  3 , Zayam Shahid  4 , Sharen Shibu  5 , Muhammad Usman  6 , Noor Abbas  7
Affiliations
Review

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Vitamin K Antagonists in Elderly Patients With Atrial Fibrillation: A Systematic Review

Hafsa Aman et al. Cureus. .

Abstract

Anticoagulant therapy plays a pivotal role in preventing stroke and thromboembolic complications in elderly patients with atrial fibrillation, a population at increased risk for both ischemic and bleeding events. This systematic review evaluates the comparative efficacy and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in elderly patients with nonvalvular atrial fibrillation. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included only English-language randomized controlled trials (RCTs) focusing on patients aged 70 years or older. Five high-quality RCTs met the eligibility criteria. The findings consistently support the non-inferiority or superiority of DOACs compared to warfarin in preventing stroke, with a significantly lower risk of intracranial hemorrhage. However, a higher incidence of extracranial bleeding, particularly gastrointestinal bleeding, was observed with certain DOACs, especially at higher doses in patients aged 80 years and older. The review also highlights a possible role of anticoagulation in cognitive protection, although current evidence is limited. Overall, DOACs appear to be an effective and generally safer alternative to VKAs in elderly patients, but individualized treatment decisions remain essential, particularly in those with advanced age, renal impairment, or elevated bleeding risk.

Keywords: anticoagulation; atrial fibrillation; bleeding risk; cognitive outcomes; direct oral anticoagulants; doacs vs vkas; elderly; randomized controlled trials; stroke prevention; warfarin.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. The PRISMA flowchart represents the study selection process.
PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; CENTRAL: Central Register of Controlled Trials; DOAC: direct oral anticoagulants
See this image and copyright information in PMC

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