Effects of direct oral anticoagulants on cardiac outcomes in atrial fibrillation: a systematic review and network meta-analysis
In brief
Edoxaban reduces myocardial infarction risk by roughly 30% versus warfarin in AF
In a network meta-analysis of nearly 1.8 million atrial-fibrillation patients, all DOACs lowered heart-attack rates compared with vitamin K antagonists, with edoxaban showing the greatest benefit-about a one-third reduction. Apixaban modestly cut major adverse cardiac events, especially in the first year, but benefits waned in patients over 75. The findings rely on indirect evidence, so prospective trials are still needed.
- Journal
- Internal and emergency medicine (Q1)
- Published
- 3 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Danilo Menichelli, Daniele Malatesta, Arianna Pannunzio, Alessio Farcomeni, Francesco Violi, Pasquale Pignatelli, et al.
- PMID
- 42547732
- DOI
- 10.1007/s11739-026-04480-1
Why clinicians should know about it
- Picked for Emergency Medicine (top studies of the week, 9 August 2026).
- Picked for Internal Medicine (top studies of the week, 9 August 2026): DOACs lower MI and MACE risk versus VKAs in AF
- Picked for Hematology (top studies of the week, 9 August 2026).
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) reduce thromboembolism in atrial fibrillation (AF), but their effect on cardiac outcomes is less studied. METHODS: Systematic review and network meta-analysis were performed on AF patients on DOACs/vitamin K antagonists (VKAs). Both observational studies and randomized clinical trials (RCTs) were included. Endpoints were myocardial infarction (MI) and major adverse cardiac events (MACE). Rankograms and SUCRA were performed. Sub-group analysis included age (</≥ 75 years) and length of follow-up (</≥ 12 months). RESULTS: 50 studies (3 RCTs, 4 post hoc analyses of RCTs and 43 observational studies) with 1,769,987 patients were included (59.9% on DOACs and 45.3% women). The MI risk (46 studies with 1,554,704 patients) was lower in all DOACs compared to VKA (apixaban: hazard ratio [HR] 0.83, 95% credible interval [95%CI 0.72-0.96], edoxaban: HR 0.68, 95%CI 0.53-0.86, rivaroxaban: HR 0.84, 95%CI 0.74-0.95, dabigatran: HR 0.85, 95%CI 0.75-0.97). SUCRA showed edoxaban as first choice for preventing MI overall. In patients aged < 75 years, a lower MI risk was found for edoxaban (HR 0.60, 95%CI 0.41-0.85), while in those aged ≥ 75 years, no significant difference was found among anticoagulants. Heterogeneity was low in all analyses. Network meta-analysis showed no differences among DOACs. Compared to VKA, apixaban (HR 0.77, 95%CI 0.63-0.97) was associated with lower MACE risk. Analysis of SUCRA showed apixaban as first choice for preventing MACE overall and in patients treated for < 12 months. CONCLUSION: DOACs were associated with a lower risk of MACE/MI in AF. The effect of DOACs on cardiovascular risk differs according to aging and follow-up length. However, our findings are based on indirect evidence, and further studies are needed. PROSPERO REGISTRATION NUMBER: CRD42023407778.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.