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ADAPT AF-DES

Appropriate Duration of Antiplatelet and Thrombotic Strategy after 12 Months in Patients with Atrial Fibrillation Treated with Drug-Eluting Stents

Year of Publication: 2025

Authors: S.-J. Lee, H.T. Yu, Y.-J. Lee, ..., and J.-S. Kim

Journal: New England Journal of Medicine

Citation: Lee S-J, Yu HT, Lee Y-J, et al. Therapy for Atrial Fibrillation in Patients with Drug-Eluting Stents. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2512091

Link: https://doi.org/10.1056/NEJMoa2512091

Clinical Question

Is NOAC monotherapy noninferior to combination therapy with NOAC plus clopidogrel in patients with atrial fibrillation who had drug-eluting stent implantation at least 1 year earlier?

Bottom Line

In patients with atrial fibrillation and drug-eluting stents implanted at least 1 year earlier, NOAC monotherapy was noninferior and superior to combination therapy for net adverse clinical events, primarily due to reduced bleeding risk without increased ischemic events.

        Major Points
        Multicenter, randomized, open-label noninferiority trial in South Korea
960 patients with atrial fibrillation and drug-eluting stents ≥1 year post-implantation
NOAC monotherapy vs NOAC plus clopidogrel combination therapy
Primary endpoint: net adverse clinical events at 12 months
Monotherapy was both noninferior (P<0.001) and superior (P<0.001) to combination therapy
Significant reduction in bleeding events with monotherapy (5.2% vs 13.2%)
No significant difference in ischemic events between groups

      

Design

Study Type: Multicenter, randomized, open-label, noninferiority trial

Randomization: 1

Blinding: Open-label (no blinding), but independent clinical-events committee was blinded to treatment assignments

Enrollment Period: April 2020 through May 2024

Follow-up Duration: 12 months

Centers: 32

Countries: South Korea

Sample Size: 960

Analysis: Intention-to-treat analysis using Kaplan-Meier method for primary endpoint and Fine-Gray subdistribution hazard model for treatment effects. SAS software version 9.4 and R software version 4.2.2

Inclusion Criteria

Age 19-85 years
Diagnosis of atrial fibrillation
PCI with second- or third-generation drug-eluting stent implantation ≥1 year before enrollment
High risk for thromboembolism (CHA2DS2-VASc score ≥2)

Exclusion Criteria

Age >85 years
Anticoagulation therapy after mechanical prosthetic valve surgery
Moderate-to-severe mitral stenosis
Deep-vein thrombosis
PCI with first-generation drug-eluting stent
History of previous intracranial hemorrhage
Recent gastrointestinal bleeding
High bleeding risk
Severe anemia or thrombocytopenia
Active cancer or life expectancy <1 year

Arms

Field	NOAC Monotherapy	Control
Intervention	Apixaban 5mg twice daily or rivaroxaban 20mg once daily (with dose reductions per prespecified criteria)	Apixaban 5mg twice daily or rivaroxaban 15mg once daily plus clopidogrel 75mg once daily (with dose reductions per prespecified criteria)
Duration	12 months	12 months

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Net adverse clinical events: composite of death from any cause, myocardial infarction, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding at 12 months	Primary	82 patients (17.2%)	46 patients (9.6%)	0.54	<0.001 for noninferiority and superiority
Death from any cause	Secondary	19 patients (4.0%)	14 patients (2.9%)	0.73
Cardiovascular death	Secondary	11 patients (2.3%)	7 patients (1.5%)	0.63
Myocardial infarction	Secondary	6 patients (1.3%)	4 patients (0.8%)	0.66
Stent thrombosis	Secondary	2 patients (0.4%)	2 patients (0.4%)	0.99
Stroke	Secondary	4 patients (0.8%)	5 patients (1.0%)	1.24
Major bleeding	Secondary	29 patients (6.1%)	11 patients (2.3%)	0.37
Clinically relevant nonmajor bleeding	Secondary	34 patients (7.1%)	14 patients (2.9%)	0.4
Major bleeding or clinically relevant nonmajor bleeding	Adverse	63 patients (13.2%)	25 patients (5.2%)	0.38

Subgroup Analysis

Subgroup analyses showed consistent results across age groups, sex, time since PCI, clinical presentation, NOAC type, CHA2DS2-VASc score, HAS-BLED score, complex PCI status, and drug-eluting stent generation

Criticisms

Open-label trial design may introduce bias
Lower-than-anticipated event rates may have reduced statistical power
Trial designed for noninferiority, so superiority findings should be interpreted with caution
Only apixaban and rivaroxaban used, limiting generalizability to other NOACs
Higher incidence of inappropriate NOAC underdosing in combination group (29.0% vs 11.3%)
Single-country study in East Asian population may limit generalizability to other populations
Relatively short 12-month follow-up period
Reduced rivaroxaban dose (15mg) in combination group based on previous trial

Funding

Cardiovascular Research Center and Samjin Pharmaceutical

Based on: ADAPT AF-DES (New England Journal of Medicine, 2025)

Authors: S.-J. Lee, H.T. Yu, Y.-J. Lee, ..., and J.-S. Kim

Citation: Lee S-J, Yu HT, Lee Y-J, et al. Therapy for Atrial Fibrillation in Patients with Drug-Eluting Stents. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2512091

Content summarized and formatted by NeuroTrials.ai.

ADAPT AF-DES

(2025)

Objective

To investigate whether NOAC monotherapy is noninferior to combination therapy with a NOAC plus clopidogrel in patients with atrial fibrillation after implantation of drug-eluting stents at least 1 year earlier

Study Summary

• NOAC monotherapy was noninferior and superior to combination therapy for net adverse clinical events (9.6% vs 17.2%)
• Major bleeding significantly reduced with monotherapy (5.2% vs 13.2%)
• Similar rates of ischemic events between groups

Intervention

NOAC monotherapy (apixaban 5mg BID or rivaroxaban 20mg daily) vs combination therapy (NOAC plus clopidogrel 75mg daily)

Inclusion Criteria

Atrial fibrillation patients aged 19-85 years with drug-eluting stent implantation ≥1 year prior, CHA2DS2-VASc score ≥2

Study Design

Arms: NOAC monotherapy (482 patients) vs NOAC plus clopidogrel combination therapy (478 patients)

Patients per Arm: 482 vs 478

Outcome

• Primary endpoint (net adverse clinical events): 9.6% vs 17.2% (HR 0.54, P<0.001)
• Major bleeding: 2.3% vs 6.1% (HR 0.37)
• No difference in cardiovascular death, MI, or stroke between groups

Bottom Line

Major Points

Multicenter, randomized, open-label noninferiority trial in South Korea
960 patients with atrial fibrillation and drug-eluting stents ≥1 year post-implantation
NOAC monotherapy vs NOAC plus clopidogrel combination therapy
Primary endpoint: net adverse clinical events at 12 months
Monotherapy was both noninferior (P<0.001) and superior (P<0.001) to combination therapy
Significant reduction in bleeding events with monotherapy (5.2% vs 13.2%)
No significant difference in ischemic events between groups

Study Design

Study Type: Multicenter, randomized, open-label, noninferiority trial
Randomization: Yes
Blinding: Open-label (no blinding), but independent clinical-events committee was blinded to treatment assignments
Sample Size: 960
Follow-up: 12 months
Centers: 32
Countries: South Korea

Primary Outcome

Definition: Net adverse clinical events: composite of death from any cause, myocardial infarction, stent thrombosis, stroke, systemic embolism, or major bleeding or clinically relevant nonmajor bleeding at 12 months

Control	Intervention	HR/OR	P-value
82 patients (17.2%)	46 patients (9.6%)	0.54 (0.37 to 0.77)	<0.001 for noninferiority and superiority

Limitations & Criticisms

Open-label trial design may introduce bias
Lower-than-anticipated event rates may have reduced statistical power
Trial designed for noninferiority, so superiority findings should be interpreted with caution
Only apixaban and rivaroxaban used, limiting generalizability to other NOACs
Higher incidence of inappropriate NOAC underdosing in combination group (29.0% vs 11.3%)
Single-country study in East Asian population may limit generalizability to other populations
Relatively short 12-month follow-up period
Reduced rivaroxaban dose (15mg) in combination group based on previous trial

Citation

Lee S-J, Yu HT, Lee Y-J, et al. Therapy for Atrial Fibrillation in Patients with Drug-Eluting Stents. N Engl J Med. 2025. DOI: 10.1056/NEJMoa2512091

View Original Publication →

ADAPT AF-DES

Appropriate Duration of Antiplatelet and Thrombotic Strategy after 12 Months in Patients with Atrial Fibrillation Treated with Drug-Eluting Stents

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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