SAN DIEGO, CA—There is no late benefit in prolonging combination therapy with clopidogrel and a non-vitamin K antagonist oral anticoagulant (NOAC) in patients with atrial fibrillation (AF) who previously underwent coronary revascularization, according to an extended follow-up of the ADAPT AF-DES trial.
Yong-Joon Lee, MD, PhD (Severance Hospital/Yonsei University College of Medicine, Seoul, South Korea), who presented the results during the Worldlink featured clinical research session at TCT 2026, said the follow-up data showed that continuing with clopidogrel therapy beyond 1 year in AF patients treated with a drug-eluting stent (DES) provides no “delayed protection” against major ischemic events.
“Our study supports NOAC beyond 1 year as the appropriate strategy to balance between bleeding and ischemia risk in patients with [AF] and DES implantation,” he said.
At 2 years, net adverse clinical events (NACE), a composite of death from any cause, MI, stent thrombosis, stroke, systemic embolism, or major or clinically relevant nonmajor bleeding, occurred in 16.0% of patients treated with the NOAC alone and 26.4% of those who received combination therapy (HR 0.57; 95% CI 0.43-0.75). The difference in NACE was the result of a higher risk of major and clinically relevant nonmajor bleeding.
ADAPT AF-DES investigators previously showed that there was no benefit—only harm—in treating AF patients who had undergone PCI with a DES at least 1 year earlier with a NOAC and clopidogrel. The 12-month risk of NACE was significantly higher in those treated with combination therapy, a difference resulting from higher risks of both major and clinically relevant nonmajor bleeding.
Sang Yeub Lee, MD, PhD (Chung-Ang University Gwangmyeong Hospital, South Korea), the discussant following today’s presentation, said the main criticism of ADAPT AF-DES had been its “timing.”
“The bleeding risk is front-loaded while the ischemic risk keeps building,” he said. “So, 1 year might [have been] too short to see [differences in] myocardial infarction or stent thrombosis. Today’s 2-year data speak directly to that.”
Session moderator Marco Valgimigli, MD, PhD (Cardiocentro Ticino Institute, Lugano, Switzerland), said these new data should close the book on the need for further study. “Is it time to stop randomizing patients after 12 months to monotherapy versus combination therapy?” he asked. “I think the story is over. I will not keep randomizing patients.”
The extended follow-up was published simultaneously in the New England Journal of Medicine as a research letter.
Oral Anticoagulation Alone Recommended
Patients with AF undergoing PCI for stable coronary artery disease or ACS are frequently encountered in clinical practice. With an abundance of data from several trials, including OAC-ALONE, AFIRE, and AQUATIC, showing that oral anticoagulation alone should be preferred, the latest US guidelines for diagnosing and managing AF recommend oral anticoagulation alone in patients who are a year out from PCI (class I, level of evidence B-R).
ADAPT AF-DES was a contemporary non-inferiority study of 960 patients (mean age 71.1 years; 21.4% women) with AF who were a year removed from revascularization with a second- or third-generation DES (median time 32.8 months). Patients were randomized to monotherapy with a NOAC or combination treatment with a NOAC plus clopidogrel. Approximately two-thirds of patients were treated with apixaban (Eliquis, Bristol Myers Squibb) and one-third were treated with rivaroxaban (Xarelto, Johnson & Johnson). The mean CHA2DS2-VASc score was 4.1 at baseline.
Like the 12-month outcomes, the lower 2-year rate of NACE with the NOAC alone was driven by lower risk of major or clinically relevant nonmajor bleeding (10.6% vs 22.0%; HR 0.45; 95% CI 0.32-0.73). Cardiovascular mortality was lower with NOAC monotherapy (1.5% vs 3.6%; HR 0.41; 95% CI 0.17-0.98), although investigators cautioned against overinterpreting the finding given the small number of events: 7 vs 17 cardiovascular deaths with combination therapy.
During his presentation, Lee said that while the extended follow-up was open label, which may have influenced the findings, 87% of patients had already completed 2-year follow-up before the 1-year results were presented and published. Despite the limitations, including enrollment of only South Korean patients, panelists largely consider the appropriate antithrombotic strategy a settled question in this patient group.
Not everybody was fully convinced, though. Panelist Jeehoon Kang, MD, PhD (Seoul National University Hospital, South Korea), pointed out that patients in ADAPT AF-DES were randomized roughly 2 to 3 years after revascularization. “In my opinion, we still don’t have enough evidence that we can stop clopidogrel at 1 year,” he said. “We still need evidence for that.”
Source
Lee S-H, Lee Y-J, Heo JH, et al. Extended outcomes of the ADAPT AF-DES trial. N Engl J Med. Published online October 31, 2026.
Lee S-H, Yu HT, Lee Y-J, et al. Therapy for atrial fibrillation in patients with drug-eluting stents. N Engl J Med. 2026;394:658-668.
Disclosures
Yong-Joon Lee, Sang Yeub Lee, and Kang report no conflicts of interest.
Valgimigli reports grant support/research contracts from Om Pharma, Concept Medical, Cordis, and the Swiss National Science Foundation. He reports consulting fees/honoraria from AstraZeneca, Biotronik, Chiesi, Abbott, Terumo Medical, Concept Medical, Daiichi -Sankyo/Eli Lilly, Janssen Pharmaceuticals, Om Pharma, Corflow, Idorsia, Novartis, Alvimedica, Vesalio, and Cordis.