Highlight
– In ADAPT AF‑DES (N=960), NOAC monotherapy was noninferior to NOAC plus clopidogrel for net adverse clinical events at 12 months and demonstrated superiority (absolute difference −7.6 percentage points; HR 0.54).
– Major or clinically relevant nonmajor bleeding was markedly lower with NOAC alone (5.2% vs 13.2%; HR 0.38).
– The trial addresses a common clinical dilemma—long‑term antithrombotic strategy beyond 1 year after DES implantation in patients with atrial fibrillation—and provides high‑quality randomized data supporting de‑escalation to NOAC monotherapy.
Background and clinical context
Atrial fibrillation (AF) and coronary artery disease frequently coexist. After percutaneous coronary intervention (PCI) with drug‑eluting stents (DES), patients with AF require oral anticoagulation to reduce stroke risk in addition to antiplatelet therapy to prevent stent thrombosis and recurrent coronary events. Early after PCI, combination regimens (dual or triple antithrombotic therapy) are often necessary but increase bleeding. Contemporary trials have shown that among patients with AF undergoing PCI, regimens that include a non‑vitamin K antagonist oral anticoagulant (NOAC) plus a single P2Y12 inhibitor reduce bleeding compared with vitamin K antagonist–based triple therapy, without clear excess ischemic events.
However, the optimal long‑term management beyond the first year after stent implantation remains uncertain. Many clinicians continue combination therapy (anticoagulant plus single antiplatelet agent) long term out of concern for late stent thrombosis or recurrent ischemic events, while others favor anticoagulation alone to minimize bleeding. The ADAPT AF‑DES randomized trial directly addresses this gap by comparing NOAC monotherapy with NOAC plus clopidogrel in patients with AF who had a DES implanted at least 1 year earlier.
Study design and methods
ADAPT AF‑DES was a multicenter, randomized, open‑label, noninferiority trial conducted in South Korea. Eligible patients had atrial fibrillation and had undergone implantation of a drug‑eluting stent at least 1 year before enrollment. Patients were randomized 1:1 to receive either NOAC monotherapy or combination therapy (NOAC plus clopidogrel). The trial was pragmatic in design and inclusive of patients receiving standard NOAC therapy as per local practice; the protocol compared continuation of anticoagulation alone versus anticoagulation plus clopidogrel.
The primary end point was net adverse clinical events (NACE), a composite of death from any cause, myocardial infarction, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding at 12 months. The trial tested a noninferiority hypothesis with a prespecified margin of 3.0 percentage points for the absolute difference in 12‑month event rates. Secondary outcomes included individual components of the composite endpoint and safety events, particularly bleeding.
Key findings
A total of 960 patients underwent randomization: 482 to NOAC monotherapy and 478 to combination therapy. The mean age was 71.1 years; 21.4% were women.
At 12 months the Kaplan‑Meier estimate for the primary composite end point was 9.6% in the monotherapy group (46 events) and 17.2% in the combination‑therapy group (82 events). The absolute difference was −7.6 percentage points (95.2% confidence interval [CI], −11.9 to −3.3); the trial met the prespecified noninferiority criterion (P<0.001) and, on hypothesis testing, demonstrated superiority for NOAC monotherapy (hazard ratio [HR] 0.54; 95.2% CI, 0.37 to 0.77; P<0.001 for superiority).
Bleeding outcomes drove much of the difference between the groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 25 patients (5.2%) in the monotherapy group versus 63 patients (13.2%) in the combination‑therapy group (HR 0.38; 95% CI, 0.24 to 0.60). This represents a substantial absolute reduction in clinically important bleeding with discontinuation of single antiplatelet therapy.
Reported ischemic outcomes (myocardial infarction, stent thrombosis, stroke, systemic embolism) did not increase with NOAC monotherapy; the composite net outcome favored monotherapy driven primarily by fewer bleeding events. The trial was not large enough to provide precise estimates for rare events such as stent thrombosis, but no signal of excess ischemia was detected in the prespecified analyses.
Interpretation of effect sizes and clinical significance
The observed absolute reduction in the 12‑month NACE of 7.6 percentage points—driven mainly by bleeding—exceeds the trial’s noninferiority margin and is clinically meaningful. The bleeding hazard ratio (0.38) indicates a roughly 60% relative reduction in major or clinically relevant nonmajor bleeding when antiplatelet therapy is discontinued. For clinicians, these magnitudes suggest that, for many stable patients with AF and a DES implanted ≥1 year earlier, continuation of NOAC alone will reduce harm without apparent trade‑off in ischemic protection.
Expert commentary, mechanisms, and guideline context
ADAPT AF‑DES extends the evidence base provided by prior randomized trials of antithrombotic strategies in AF patients undergoing PCI (PIONEER AF‑PCI, RE‑DUAL PCI, AUGUSTUS, ENTRUST‑AF‑PCI), which primarily addressed the early post‑PCI period and supported NOAC‑based strategies with reduced bleeding compared with VKA‑based triple therapy. Those studies largely focused on the initial weeks to months after PCI; ADAPT AF‑DES specifically tests the late post‑PCI management strategy, a clinically important question given the chronic nature of AF and the prolonged antiplatelet use that persists in many patients.
Biologic plausibility for de‑escalation after 1 year is strong. By 12 months most stents are fully endothelialized and the risk of device‑related thrombosis is low in the absence of other prothrombotic conditions. Long‑term antiplatelet therapy therefore offers diminishing marginal benefit for prevention of stent‑related events but continues to add bleeding risk when combined with systemic anticoagulation.
Current international guidelines recommend balancing ischemic and bleeding risks and generally favor minimizing the duration of combination therapy after PCI in patients requiring anticoagulation. However, explicit guidance about routine discontinuation of antiplatelet therapy beyond the first year has been limited by lack of randomized data until now. ADAPT AF‑DES provides randomized evidence supporting NOAC monotherapy as a reasonable standard approach in appropriately selected patients at ≥1 year after DES implantation.
Limitations and considerations
Several limitations should be considered when applying these results to practice. The trial was open‑label, which may influence reporting of subjective outcomes, although hard events (death, MI, stroke) are less susceptible. The study was conducted in South Korea, and the enrolled population, antiplatelet responsiveness, genetic factors, and practice patterns may differ from other regions; external validity should be considered, though biologic effects are likely generalizable.
Notably, the trial compared NOAC monotherapy to NOAC plus clopidogrel only; other antiplatelet agents (e.g., prasugrel, ticagrelor) were not part of the randomized comparison. High‑ischemic‑risk subgroups—extensive stent thrombosis history, recent acute coronary syndrome, complex bifurcation stenting, or left main stenting—may merit individualized decisions and were likely underrepresented. The trial report does not provide full detail on the breakdown of NOAC agents, dosing strategies, or strict criteria for high ischemic risk; clinicians should review the full manuscript and supplementary materials when applying results to patients with higher baseline ischemic risk or competing indications for antiplatelet therapy.
Finally, rare events such as late stent thrombosis are uncommon and even randomized trials of this size remain underpowered for definitive statements about very low‑frequency ischemic complications. Ongoing post‑marketing surveillance and meta‑analyses incorporating ADAPT AF‑DES with prior trials will refine absolute risk estimates further.
Implications for practice and next steps
For patients with atrial fibrillation who have been >1 year out from uncomplicated DES implantation and who have no other indication for antiplatelet therapy, ADAPT AF‑DES supports stopping clopidogrel and continuing a NOAC alone. This approach substantially lowers bleeding without evidence of increased ischemic events at 12 months and should be discussed with patients when weighing risks and benefits.
Where uncertainty remains—recent ACS, high‑burden left main or complex stenting, prior stent thrombosis, or coexisting high thrombotic risk—individualized decisions remain prudent and shared decision‑making is essential. Future guideline updates will likely incorporate these data and may give firmer recommendations on routine de‑escalation to anticoagulant monotherapy beyond 1 year after DES implantation.
Conclusion
ADAPT AF‑DES provides randomized evidence that, among patients with atrial fibrillation and a drug‑eluting stent implanted at least one year earlier, NOAC monotherapy is noninferior to NOAC plus clopidogrel for a composite of ischemic and bleeding outcomes at 12 months and is associated with substantially less bleeding. These findings support clinician consideration of NOAC monotherapy as a standard long‑term strategy in appropriately selected stable patients.
Funding and trial registration
The trial was funded by the Cardiovascular Research Center and Samjin Pharmaceutical. ClinicalTrials.gov number: NCT04250116.
References
1. Lee SJ, Yu HT, Lee YJ, et al.; ADAPT AF‑DES Investigators. Therapy for Atrial Fibrillation in Patients with Drug‑Eluting Stents. N Engl J Med. 2025 Nov 8. doi:10.1056/NEJMoa2512091. Epub ahead of print. PMID: 41211917.
2. Gibson CM, Mehran R, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med. 2016; (PIONEER AF‑PCI).
3. Cannon CP, et al. Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation. N Engl J Med. 2017; (RE‑DUAL PCI).
4. Lopes RD, et al. Antithrombotic Therapy After Acute Coronary Syndromes or PCI in Patients with Atrial Fibrillation. N Engl J Med. 2019; (AUGUSTUS).
5. Vranckx P, et al. Edoxaban-based Regimen vs Vitamin K Antagonist in Patients with AF after PCI. N Engl J Med. 2019; (ENTRUST‑AF PCI).
6. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation. Eur Heart J. 2020; (ESC AF Guidelines).
Note: For full reference details and page numbers consult the individual publications and guideline documents.
