# Add-on antiplatelet therapy in anticoagulated patients with atrial fibrillation

**Authors:** Yuki Matsuoka, Hitoshi Minamiguchi, Daisuke Sakamoto, Akihiro Sunaga, Katsuki Okada, Daisaku Nakatani, Tetsuhisa Kitamura, Takashi Kanda, Ryuta Watanabe, Kouichi Nagashima, Yoshiharu Higuchi, Yasuo Okumura, Yohei Sotomi, Yasushi Sakata

PMC · DOI: 10.1016/j.ijcha.2026.101907 · 2026-03-20

## TL;DR

Adding antiplatelet therapy to anticoagulation in atrial fibrillation patients increases risks of both ischemic events and bleeding.

## Contribution

Large real-world data analysis shows increased risks of combined antiplatelet and anticoagulant therapy in AF patients.

## Key findings

- Add-on antiplatelet therapy increased ischemic event risk by 28% compared to anticoagulation alone.
- Bleeding risk was 26% higher in patients receiving combined therapy.
- Findings are not generalizable to the early post-PCI/CABG period.

## Abstract

The impact of add-on antiplatelet therapy in patients with atrial fibrillation (AF) on oral anticoagulants (OAC) in real-world clinical practice remains to be investigated.

We conducted DIRECT-Extend registry, a pooled analysis combining three large-scale real-world datasets of non-valvular AF patients treated with anticoagulation. We assessed clinical impacts of the add-on antiplatelet therapy using the inverse-probability-of-treatment weighting methods. Antiplatelet therapy included aspirin, P2Y12 inhibitors, and cilostazol (dual therapy included). The primary ischemic endpoint was a composite of all-cause death, ischemic stroke, systemic embolism, and myocardial infarction. The primary bleeding endpoint was any bleeding, defined as a composite of major bleeding and clinically relevant non-major bleeding according to the criteria of the International Society on Thrombosis and Hemostasis.

A total 7387 eligible patients (excluding those within 1 year after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)) were divided into two groups: the OAC alone group (N = 6096) and the OAC + APT group (treated with both OAC and antiplatelet therapy, N = 1291). The median follow-up period was 1012 [404, 1344] days. The risk for both the primary ischemic and bleeding endpoint was higher in patients in OAC + APT group than those in OAC alone group (ischemic endpoint, weighted hazard ratio (wHR): 1.28, 95%CI [1.17 – 1.40], p < 0.001; bleeding endpoint, wHR: 1.26 [1.19–1.33], p < 0.001).

The large-scale real-world data demonstrated that, in AF patients treated with OAC, add-on antiplatelet therapy was associated with a higher risk for both ischemic and bleeding endpoints. These findings may not be generalizable to the early post-PCI/CABG period.

## Linked entities

- **Chemicals:** aspirin (PubChem CID 2244), cilostazol (PubChem CID 2754)
- **Diseases:** atrial fibrillation (MONDO:0004981), ischemic stroke (MONDO:1060198), myocardial infarction (MONDO:0005068)

## Full-text entities

- **Diseases:** ischemic (MESH:D002545), AF (MESH:D001281), myocardial infarction (MESH:D009203), Thrombosis (MESH:D013927), systemic embolism (MESH:D004617), death (MESH:D003643), ischemic stroke (MESH:D002544), bleeding (MESH:D006470)
- **Chemicals:** aspirin (MESH:D001241), cilostazol (MESH:D000077407), Antiplatelet (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13018862/full.md

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Source: https://tomesphere.com/paper/PMC13018862