Effects of omitting antiplatelet agent in anticoagulation-treated AF patients with stable CAD

In a systematic review and meta-analysis of 4 open-label RCTs among patients with AF and stable coronary artery disease (CAD), OAC monotherapy was associated with reduced bleeding risk but no increased risk of ischemic events compared with OAC plus antiplatelet therapy.

This summary is based on the publication of Rashedi S, Keykhaei M, Sato A, et al. - Anticoagulation and Antiplatelet Therapy for Atrial Fibrillation and Stable Coronary Disease: Meta-Analysis of Randomized Trials. J Am Coll Cardiol. 2025 Mar 25;85(11):1189-1203. doi: 10.1016/j.jacc.2024.12.030.

Introduction and methods

Background

For patients with AF and stable coronary artery disease (CAD), both oral anticoagulation (OAC) and single antiplatelet therapy (SAPT) are indicated [1-4]. However, the best long-term antithrombotic strategy for balancing ischemic and bleeding risks remains uncertain [5]. Recent RCTs have shown conflicting results on the risk of ischemic events and were not individually powered for this outcome [6-9]. Previous pooled analyses also had their limitations, such as lack of prespecified methods, exclusion of some relevant RCTs, and inability to evaluate results in subgroups [10,11].

Aim of the study

The study aim was to compare the effectiveness and safety of OAC monotherapy versus OAC plus SAPT in patients with AF and stable CAD and prespecified potential prognostic subgroups, based on pooled RCT results.

Methods

In a systematic review and study-level meta-analysis based on a prespecified protocol and rigorous statistical methods, a collaborative group of researchers performed systematic searches in PubMed, Embase, and ClinicalTrials.gov until September 9, 2024, to identify RCTs investigating OAC monotherapy versus OAC plus SAPT in patients with stable CAD and AF. Of the 690 screened records, 4 published open-label RCTs, all conducted in East Asia, were included (total n=4092): EPIC-CAD (Edoxaban vs Edoxaban with Antiplatelet agent in Patients with Atrial Fibrillation and Chronic Stable Coronary Artery Disease; OAC monotherapy was edoxaban), PRAEDO-AF (Prospective Randomized Study of Safety Outcomes Treated with Edoxaban in Patients with Stable Coronary Artery Disease and Atrial Fibrillation; edoxaban), AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease; rivaroxaban), and OAC-ALONE (Optimizing Antithrombotic Care in Patients With Atrial Fibrillation and Coronary Stent; warfarin, dabigatran, rivaroxaban, apixaban or edoxaban) [8-11]. Median follow-up durations ranged from 12 to 30 months (overall estimated weighted mean follow-up time: 21.9 months).

Outcomes

The primary effectiveness endpoint was a composite outcome of MI, ischemic stroke, systemic embolism, or all-cause mortality. Secondary effectiveness endpoints were the individual components of the primary effectiveness endpoint, CV death, and unplanned coronary revascularization.

The primary safety endpoint comprised major bleeding events according to the International Society on Thrombosis and Haemostasis (ISTH) definition. An additional safety endpoint was a composite outcome of major or clinically relevant nonmajor bleeding events according to the ISTH definitions.

Main results

Effectiveness

• The occurrence of the primary effectiveness endpoint did not differ between patients treated with OAC monotherapy (n=2049) and those receiving OAC plus SAPT (n=2043) (7.3% vs. 8.2%; HR: 0.90; 95%CI: 0.72–1.12; P=0.34), with moderate heterogeneity between trials (I²=45%).
• There were also no differences in the risks of MI (1.0% vs. 0.7%; HR: 1.51; 95%CI: 0.75–3.04; P=0.25; I²=0%), ischemic stroke (1.9% vs. 2.1%; HR: 0.89; 95%CI: 0.57–1.37; P=0.59; I²=0%), systemic embolism (0.15% vs. 0.15%; HR: 0.94; 95%CI: 0.81–1.09; P=0.43; I²=0%), all-cause mortality (4.2% vs. 5.3%; HR: 0.94; 95%CI: 0.49–1.80; P=0.84; I²=65%), CV death (2.4% vs. 3.0%; HR: 0.79; 95%CI: 0.54–1.15; P=0.22; I²=22%), and unplanned coronary revascularization (1.4% vs. 1.4%; HR: 0.98; 95%CI: 0.58–1.64; P=0.93; I²=0%) between the OAC monotherapy and OAC plus SAPT groups.

Safety

• The use of OAC monotherapy was associated with lower risks of major bleeding events (3.3% vs. 5.7%; HR: 0.59; 95%CI: 0.44–0.79; P<0.001; I²=0%) and major or clinically relevant nonmajor bleeding events (10.0% vs. 18.4%; HR: 0.53; 95%CI: 0.44–0.63; P<0.001; I²=58%) compared with OAC plus SAPT.

Subgroup analyses

• Subgroup analysis indicated consistent results for the primary effectiveness endpoint across subgroups stratified by age, sex, presence of diabetes, CHA₂DS₂-VASc score, prior PCI, or antiplatelet agent (all P for interaction>0.05).
• For the primary safety endpoint, subgroup analysis did not show effect modification in the prespecified subgroups, except for a larger reduction in bleeding risk with OAC monotherapy compared with OAC plus SAPT in men (HR: 0.46; 95%CI: 0.34–0.62) than women (HR: 0.92; 95%CI: 0.52–1.63; P for interaction=0.03) and in patients with diabetes (HR: 0.44; 95%CI: 0.26–0.73) than those with no diabetes (HR: 0.86; 95%CI: 0.57–1.30; P for interaction=0.04).

Conclusion

In this systematic review and meta-analysis of 4 open-label RCTs among patients with AF and stable CAD, OAC monotherapy was associated with a reduced risk of major bleeding events but no increased risk of ischemic events compared with OAC plus SAPT. The magnitude of bleeding risk reduction with OAC monotherapy seemed to be greater in men and patients with diabetes.

Find this article online at J Am Coll Cardiol.

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