Clopidogrel Monotherapy Versus Extended DAPT in High-Ischemic-Risk Stent Patients: The A-CLOSE Trial

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Summary of  New England Journal of Medicine https://doi.org/10.1056/NEJMoa2608533
Dr. Seung-Jun Lee et al.

Points

Severance Cardiovascular Hospital researchers evaluated clopidogrel monotherapy versus extended dual antiplatelet therapy across nineteen South Korean centers in high-risk patients 12 months post-stent.
Enrollment encompassed 3,203 participants with high-risk clinical or lesion characteristics, featuring a mean age of 63 years and 18.4 percent female representation.
Primary net adverse clinical event rates at twenty-four months demonstrated noninferiority for clopidogrel monotherapy compared to extended dual antiplatelet therapy at 5.0 percent versus 5.1 percent.
Secondary ischemic outcome analysis revealed significantly higher rate occurrences under clopidogrel monotherapy at 3.7 percent compared to 1.6 percent for extended dual antiplatelet therapy.
Safety end points showed clopidogrel monotherapy markedly reduced major or clinically relevant bleeding to 1.8 percent compared to 4.1 percent under extended therapy.

Summary

This study evaluated the safety and clinical efficacy of clopidogrel monotherapy versus extended dual antiplatelet therapy (DAPT) in patients at high ischemic risk 12 months after drug-eluting stent implantation. Led by Byeong-Keuk Kim of Severance Cardiovascular Hospital and presented at ESC Congress 2026 and published in the New England Journal of Medicine, the multicenter A-CLOSE trial evaluated 3,203 participants across 19 centers in South Korea. The study sought to determine whether switching to single antiplatelet therapy could optimize outcomes by reducing bleeding risks without compromising protection against major ischemic adverse events.

The study population comprised high-risk patients with a mean age of 63 years (18.4% women) displaying high-risk clinical or lesion characteristics, randomized to clopidogrel monotherapy or extended DAPT for 24 months. At 24 months, clopidogrel monotherapy met the primary noninferiority endpoint for net adverse clinical events compared to extended DAPT (5.0% vs. 5.1%; p = 0.001 for noninferiority). However, major ischemic endpoints occurred significantly more frequently in the clopidogrel monotherapy group (3.7% vs. 1.6%; p < 0.001), including higher all-cause mortality (1.3% vs. 0.4%).

Safety outcomes demonstrated that clopidogrel monotherapy significantly reduced Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events compared to extended DAPT (1.8% vs. 4.1%; p < 0.001). The authors concluded that while clopidogrel monotherapy reduces major bleeding, extended DAPT offers superior protection against major ischemic events and mortality. These findings emphasize that long-term antiplatelet regimens following percutaneous coronary intervention must be individualized based on specific patient ischemic and bleeding risk profiles.

Link to the article: https://www.nejm.org/doi/10.1056/NEJMoa2608533

References

Lee, Seung-Jun, et al. “Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients.” New England Journal of Medicine, Aug. 2026, p. NEJMoa2608533. DOI.org (Crossref), https://doi.org/10.1056/NEJMoa2608533