Early vs later non-vitamin K antagonist oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation: A meta-analysis and systematic review of randomized trials

Fu et al., 2025 | Heart Rhythm | Meta Analysis

Citation

Fu Linghua, Hu Jinzhu, ... Chen Qi. Early vs later non-vitamin K antagonist oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation: A meta-analysis and systematic review of randomized trials. Heart Rhythm. 2025-Mar;22(3):629-636. doi:10.1016/j.hrthm.2024.12.008

Abstract

BACKGROUND: There are conflicting published data on the optimal timing of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with acute ischemic stroke. OBJECTIVE: To compare the efficacy and safety of early initiation of NOACs with later initiation of NOACs in those patients, we conducted a meta-analysis of phase 3 or phase 4 randomized controlled trials. METHODS: We systematically searched the Cochrane Library, PubMed, and Embase databases. A random effects model was selected to pool the effect measurement estimates (risk ratios [RRs] and 95% confidence intervals [CIs]). RESULTS: Three randomized controlled trials with 6442 enrolled patients with AF and acute ischemic stroke were included. Compared with later NOAC therapy, early NOAC therapy was associated with nonsignificant reductions in the risk of primary outcomes (RR, 0.82; 95% CI, 0.65-1.05). Subgroup analysis found that in reducing risk of primary outcomes, early anticoagulation may benefit female patients more than male patients (0.54 [0.35-0.83] vs 0.97 [0.63-1.50]; P for interaction, .06). Numerically lower rates of recurrent ischemic stroke (RR, 0.80; 95% CI, 0.56-1.15), death (RR, 0.96; 95% CI, 0.81-1.15), and systemic embolism (RR, 0.43; 95% CI, 0.16-1.11) were observed in early initiation of NOACs in comparison with later initiation of NOACs. There was no difference in major bleeding (RR, 0.98; 95% CI, 0.55-1.74), symptomatic intracranial hemorrhage (RR, 0.93; 95% CI, 0.43-1.96), or major extracranial bleeding (RR, 0.73; 95% CI, 0.28-1.95) between groups. CONCLUSION: In AF patients with acute ischemic stroke, early initiation of NOACs is not inferior to later initiation of NOACs in reducing composite events, without increased hazard of bleeding, especially in female patients.

Key Findings

Three randomized controlled trials with 6442 enrolled patients with AF and acute ischemic stroke were included. Compared with later NOAC therapy, early NOAC therapy was associated with nonsignificant reductions in the risk of primary outcomes (RR, 0.82; 95% CI, 0.65-1.05). Subgroup analysis found that in reducing risk of primary outcomes, early anticoagulation may benefit female patients more than male patients (0.54 [0.35-0.83] vs 0.97 [0.63-1.50]; P for interaction, .06). Numerically lower rat

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population acute ischemic stroke
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Atrial Fibrillation
  • Anticoagulants
  • Ischemic Stroke
  • Administration, Oral
  • Randomized Controlled Trials as Topic

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Systematic Review, Meta-Analysis
  • Vertical: vitamin-k

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09