Clopidogrel Alone Cuts Bleeding but Extended Dual Therapy Prevents More Deaths After Stents

Antiplatelet monotherapy reduced bleeding, but dual antiplatelet therapy (DAPT) gave greater protection against cardiovascular events in patients at high ischemic risk who had received a coronary stent 12 months earlier, according to the A-CLOSE trial, presented in a Hot Line session at ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.

Current guidelines recommend 6 to 12 months of DAPT after stent implantation, followed by long-term single antiplatelet therapy with aspirin or clopidogrel — but the optimal duration beyond 12 months remains uncertain for patients at particularly high risk of recurrent heart attacks or blood clots. The trial, conducted at 19 centres in South Korea and led by Professor Byeong-Keuk Kim of Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, randomised 3,203 such patients — mean age 63, 18.4% women — 12 months after drug-eluting stent implantation to either clopidogrel monotherapy or extended DAPT for 24 months.

After 24 months, the primary endpoint — a combination of death, heart attack, stent thrombosis, stroke, or significant bleeding — occurred in 5.0% of the clopidogrel group versus 5.1% of the extended-DAPT group, meeting the trial's criteria for noninferiority (p=0.001). But a key ischemic endpoint (death, heart attack, stent thrombosis or stroke) occurred more often with clopidogrel monotherapy than with extended DAPT: 3.7% versus 1.6%. All-cause mortality was 1.3% with clopidogrel monotherapy versus 0.4% with DAPT.

A key bleeding endpoint occurred less often with clopidogrel monotherapy than with extended DAPT: 1.8% versus 4.1%.

"Extended DAPT provided greater protection against major ischemic events, including death, whereas clopidogrel monotherapy reduced major or clinically relevant bleeding," said Kim, concluding that long-term antiplatelet therapy should be individualised according to a patient's ischemic and bleeding risks, clinical characteristics and preferences.