Clopidogrel Better Than Aspirin Long-term After PCI

People at risk of a cardiac event after a percutaneous coronary intervention (PCI) stent procedure who received long-term antiplatelet therapy with clopidogrel were 29% less likely to die than those who received aspirin, according to data from the SMART-CHOICE 3 trial. The results showed that patients were also less likely to experience a heart attack or stroke.

Current clinical guidelines issued jointly by the American College of Cardiology (ACC), American Heart Association, and Society for Cardiovascular Angiography Interventions have long suggested that patients should take both aspirin and a P2Y12 inhibitor such as clopidogrel — a strategy known as dual antiplatelet therapy — for 6 months to a year after PCI to prevent blood clots and continuing with aspirin alone.

“In our study, clopidogrel beat aspirin as a lifelong maintenance monotherapy after standard-duration dual antiplatelet therapy,” said Joo-Yong Hahn, MD, an interventional cardiologist at the Samsung Medical Center in Seoul, South Korea, who presented the SMART-CHOICE 3 results at the ACC Scientific Session 2025 in Chicago, which were simultaneously published in The Lancet.

“Based on these results, I hope that guidelines will address clopidogrel monotherapy as comparable to aspirin monotherapy or as preferred to aspirin monotherapy for patients at high risk of recurrent ischemic events,” Hahn said.

SMART-CHOICE 3 Trial

SMART-CHOICE 3 assessed 5500 patients who underwent PCI in South Korea and were at high risk for a future ischemic event because of a history of heart attack, medication-treated diabetes, or complex coronary artery lesions. After completing dual antiplatelet therapy, half of the patients were randomly assigned to continue clopidogrel and half to continue aspirin.

After a median of 2.3 years, significantly more patients in the clopidogrel group than in the aspirin group died or had experienced a heart attack or stroke (4.4% vs 6.6%). Much of the difference was driven by the large reduction in the number of heart attacks in the clopidogrel group (1.0% vs 2.2%). There was a strong tendency favoring clopidogrel in the rate of death but no significant difference in the rate of stroke. There was also no significant difference in the number of major bleeding events between the two groups.

“In general, the more potent antiplatelet therapy increases bleeding risk, but in our study, clopidogrel reduced the ischemic endpoints compared to aspirin, but without increased risk of bleeding, so it’s a very ideal result,” Hahn said.

This study adds to the discussion about the merits of aspirin relative to clopidogrel for long-term antiplatelet therapy, said Akshay Khandelwal, MD, chief of cardiovascular medicine, AHN Cardiovascular Institute in Detroit, Michigan.

Khandelwal was quick to acknowledge that more than 80% of the study participants were men, which raises concerns about the generalizability of the data. As women tend to bleed more easily than men, so “understanding how this might apply to women is important,” he said.

But it is also possible that the study underestimated the benefits of clopidogrel given that it was conducted solely in South Korea, which has a high rate of clopidogrel non-responders.

The study was funded by the pharmaceutical company Dong-A ST Co, Ltd.