Clopidogrel Beat Aspirin in Preventing Heart Attacks After PCI | ACC 2025

For patients who have undergone a procedure to unclog the arteries, clopidogrel (the generic of Plavix) was better able to reduce the risk of future cardiac events than aspirin. After a median follow-up of over two years, patients taking clopidogrel were 29% less likely than those taking aspirin to experience all-cause death, heart attack or stroke, according to findings of a new study that was presented at the American College of Cardiology Annual Scientific Session and Expo and published simultaneously in The Lancet.

Percutaneous coronary intervention, which is also known as angioplasty, is a procedure using a stent to unblock clogged arteries. Current clinical guidelines recommend that patients take both aspirin and a P2Y12 inhibitor such as clopidogrel (known as dual antiplatelet therapy, or DAPT) for six months to a year following percutaneous coronary intervention, then take aspirin alone indefinitely.

Clopidogrel and aspirin are both antiplatelet medications that interfere with the clotting activity of platelets, but they act through different mechanisms.

Joo-Yong Hahn, M.D., Ph.D.

“Data supporting the use of aspirin as a single therapy after DAPT have been debated. Clopidogrel has been suggested as a potentially superior alternative to aspirin, although the evidence is limited,” Joo-Yong Hahn, M.D., Ph.D., professor at the Division of Cardiology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, said at a press conference in which he presented the results.

This is an important study for the patients at high risk of subsequent cardiac events after percutaneous coronary intervention, Akshay Khandelwal, M.D., ACC Board Trustee, said during the press conference.

“In the last several years, there have been many trials that have looked at different and even shorter regimens of dual antiplatelet therapy, but less work has been done on looking at antiplatelet monotherapy,” said Khandelwal, who was not involved in the study. “We’ve had the suggestion that perhaps clopidogrel is better than aspirin in a combined endpoint, looking at both ischemic endpoints and safety in terms of bleeding, but not an isolated ischemic endpoint.”

The SMART-CHOICE 3 Study

Researchers in the SMART-CHOICE 3 study wanted to assess whether clopidogrel would provide more benefit to patients than aspirin after initial treatment with both medications.

They compared clopidogrel monotherapy with aspirin monotherapy for long-term maintenance therapy in patients with a high ischemic risk (previous myocardial infarction, medication-treated diabetes, or complex coronary artery lesions) who completed a standard duration of dual antiplatelet therapy after percutaneous coronary intervention.

Researchers enrolled 5,506 patients who underwent percutaneous coronary intervention at 26 sites in South Korea. Half of the patients were randomly assigned to receive clopidogrel alone and half took aspirin alone. The study assessed patients using a composite endpoint death from any cause, myocardial infarction or stroke.

Researchers found that after a median of 2.3 years, 4.4% of those taking clopidogrel and 6.6% of those taking aspirin experienced death, myocardial infarction or stroke. This difference was attributed primarily to a significant reduction in the rate of heart attacks, which occurred in 1% of those taking clopidogrel and 2.2% of those taking aspirin.

There was no significant difference in the rate of strokes between the two groups and no significant difference in the rate of major bleeding events, which was a secondary endpoint of the study.

Khandelwal also pointed out that the study included mostly men; just 18% of patients enrolled were women. “We know that women tend to bleed more easily, and so understanding how that might apply to women is important also,” he said.

The researchers plan to further analyze the results to assess whether subgroups of patients with specific cardiovascular and metabolic conditions saw any difference in the rate of adverse outcomes.

One limitation of the study was that it had an open-label design and physicians treating patients were not masked. Researchers said they minimized the risk of bias by using precise criteria for endpoint analysis and having a committee review clinical events.

Researchers also pointed out that clopidogrel may be more effective in populations other than Korean patients. Korean patients, they said, have a high prevalence of poor metabolism for clopidogrel.