Optimal antithrombotic therapy for patients with atrial fibrillation and prior stent
Monica Botros1
, Shalini Mani2, Debabrata Mukherjee1
Keywords: Antithrombotic; atrial fibrillation (AF); coronary stent; direct acting oral anticoagulant; antiplatelet
Submitted Apr 14, 2026. Accepted for publication Jun 05, 2026. Published online Jul 20, 2026.
doi: 10.21037/jtd-2026-1005
Current guidelines recommend oral anticoagulation (OAC) therapy for prevention of stroke and systemic thromboembolism in patients with atrial fibrillation (AF) and a calculated annual thromboembolic risk of ≥2% per year [e.g., congestive heart failure or left ventricular dysfunction, hypertension, age ≥75 years (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 years, sex category (CHA2DS2-VASc) score of ≥2 in men and ≥3 in women] (1). Among OAC agents, direct oral anticoagulants (DOACs) are favored over warfarin for lower risk of stroke, systemic embolism, and intracranial hemorrhage (2-4). Although DOACs are preferred over warfarin in case of no contraindication, a non-negligible number of patients are still receiving warfarin therapy due to cost/insurance barriers but details or magnitude of this patient population for recent years are not available (5). Of note, AF commonly coexists with chronic coronary disease (CCD), and seeing patients with AF at an increased risk for stroke who undergoes percutaneous coronary intervention (PCI) for CCD or acute coronary syndrome (ACS) is common in medical practice. Guidelines recommend a brief duration of triple antithrombotic therapy (TAT) (e.g., 1–4 week), followed by dual therapy with an OAC and antiplatelet monotherapy for 6 months in patients undergoing elective PCI for CCD and 12 months in patients with ACS for most patients (1). A network meta-analysis of several randomized controlled trials (RCTs) assessed the optimal duration of TAT for patients with AF and ACS or undergoing PCI and reported that short-term TAT (1 week) was associated with less bleeding, with no significant differences in ischemic episodes between treatment durations (6). However, longer term TAT may be a reasonable option for those at a high risk of stent thrombosis after PCI (e.g., complex revascularization, multivessel PCI, or a previous history of stent thrombosis) (6). Furthermore, to minimize the risk for major bleeding, guidelines recommend OAC monotherapy over combination therapy of OAC plus a single antiplatelet [aspirin or purinergic receptor P2Y, G-protein coupled, 12 (P2Y12) inhibitor] in patients with AF and CCD beyond 1 year after revascularization or CCD and without history of stent thrombosis (1). An older meta-analysis of several randomized clinical trials had demonstrated that rivaroxaban was associated with a significantly reduced risk of MI across broad range of patients including a study of patients with AF demonstrating anti-ischemic effects of a DOAC (7). Despite guideline recommendations, real-world data suggest that dual therapy with antiplatelet and OAC remains commonly prescribed beyond one year of stenting instead of OAC monotherapy (8).
Lee et al., recently evaluated monotherapy with two DOACs, either apixaban or rivaroxaban, as compared with combination therapy with a DOAC and clopidogrel, in patients with AF and CCD ≥1 year after PCI (9). The trial by Lee and colleagues reported that monotherapy with DOAC was noninferior to combination therapy for the composite of death from any cause, MI, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding at 12 months (the primary end point) (9). In a prespecified analysis, monotherapy was also found to be superior to combination therapy for this same end point. Of note, this superiority of monotherapy was primarily driven by lower major or clinically relevant nonmajor bleeding which occurred in 5.2% patients in the monotherapy group and in 13.2% in the combination therapy group (hazard ratio, 0.38; 95% confidence interval: 0.24 to 0.60). As compared to prior studies investigating optimal antithrombotic therapy in patients with AF and CCD (10-12), this trial solely enrolled patients with AF who underwent implantation of a second- or third-generation drug-eluting stent and received DOACs as the oral anticoagulant, and patients in the combination-therapy group were prescribed clopidogrel instead of aspirin as the antiplatelet agent. Table 1 enumerates major trials evaluating optimal antithrombotic therapy for stroke and ischemic risk reduction in patients with AF and CCD.
Table 1
| Study | Design | Results | Comments |
|---|---|---|---|
| OAC-ALONE Study (11) | Prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion | During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group | This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. |
| AFIRE study (12) | Multicenter, open-label trial conducted in Japan evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease | Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively | The trial was stopped early because of increased mortality in the combination-therapy group |
| EPIC-CAD study (10) | Multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease | The incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI: 0.22 to 0.53) | DOAC monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual therapy. Study included patients with bare-metal stents, who had undergone previous CABG or received medical therapy without revascularization |
| ADAPT AF-DES (9) | Multicenter, randomized, open-label, noninferiority trial in South Korea comparing DOAC monotherapy or combination therapy (DOAC+ clopidogrel) | At 12 months, a primary end-point event had occurred in 46 patients (Kaplan-Meier estimate, 9.6%) in the monotherapy group and in 82 patients (Kaplan-Meier estimate, 17.2%) in the combination-therapy group | Contemporary design with use of second- or third-generation drug-eluting stent for PCI |
ADAPT AF-DES, Appropriate Duration of Anti-Platelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug Eluting Stents; AFIRE, Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study; APT, antiplatelet therapy; CABG, coronary artery bypass surgery; CI, confidence interval; DOAC, direct acting oral anticoagulant; EPIC-CAD, Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease; OAC, oral anticoagulant; OAC-ALONE study, Optimizing Antithrombotic Care in Patients With Atrial Fibrillation and Coronary Stent; PCI, percutaneous coronary intervention.
Despite contemporary trial design, several important limitations of the study by Lee et al., should be considered while interpreting the results, including the open-label trial design, reduced statistical power due to fewer primary outcome events than anticipated, inclusion of only East Asian patients from a single country who may have different risks for ischemic events than other populations, and the relatively short follow-up (9). A prespecified secondary analysis with follow-up of up to 2 years is currently ongoing and will provide additional insight. Another limitation is the high rate of inappropriate DOAC underdosing in the ADAPT AF-DES trial that may have influenced the study’s outcomes by narrowing the difference in safety outcomes i.e., bleeding between the two groups since nearly a third of the combination-therapy patients were underdosed on DOAC (13).
Regardless of the limitations, the trial by Lee et al. adds to the growing evidence that OAC monotherapy is the preferred strategy for most patients with AF and CCD ≥1 year after PCI and is consistent with prior studies such as the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease Study (AFIRE) (12), Optimizing Antithrombotic Care in Patients With Atrial Fibrillation and Coronary Stent (OAC-ALONE study) (11), and the Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD) trials which previously showed that combination therapy in patients with CCD and AF increased risk for bleeding as compared to OAC monotherapy, with no reduction in risk for ischemic events (10). Based on the totality of the evidence, it seems reasonable to prescribe DOAC monotherapy for vast majority of patients with AF and CCD with PCI more than a year ago (14) but may not apply to patients with very high ischemic risk, recurrent stent thrombosis, complex PCI, or recent ACS. Additional studies are needed to define the ideal antithrombotic strategy for these very select patients with AF and CCD who underwent stent implantation and have the highest ischemic risk or those with prior history of stent thrombosis.
Acknowledgments
None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Thoracic Disease. The article has undergone external peer review.
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