Clopidogrel Beats Aspirin for Post-PCI Heart Attack Reduction
Seoul, Monday, 31 March 2025.
A pivotal study shows clopidogrel more effectively reduces heart attack risk than aspirin after PCI, without increasing bleeding, potentially reshaping future treatment guidelines.
Groundbreaking Research Design
The SMART-CHOICE 3 trial, conducted across 26 South Korean medical centers, involved 5,506 high-risk patients who underwent percutaneous coronary intervention (PCI). The study population, with a median age of 65 years, included 18.2% women, all of whom had either experienced a prior heart attack, were being treated for diabetes, or had complex coronary artery lesions [1]. The trial, spanning from August 2020 to July 2023, randomly assigned patients to receive either 75mg daily clopidogrel or 100mg daily aspirin following their dual antiplatelet therapy (DAPT) [2].
Significant Clinical Outcomes
After a median follow-up period of 2.3 years, the results proved remarkably favorable for clopidogrel. The study revealed that patients taking clopidogrel experienced a 2.2 percentage point reduction in adverse events compared to those on aspirin. Specifically, only 4.4% of clopidogrel patients reached the composite primary endpoint of all-cause death, myocardial infarction, or stroke, compared to 6.6% in the aspirin group [1]. Most notably, the rate of heart attacks was significantly lower in the clopidogrel group at 1%, compared to 2.2% for aspirin patients [2].
Safety Profile and Implementation
A crucial finding from the research was that clopidogrel achieved these superior results without increasing bleeding risks. Dr. Joo-Yong Hahn of Samsung Medical Center emphasized this as an ‘ideal result,’ noting that typically more potent antiplatelet therapy carries increased bleeding risks [1]. The study demonstrated identical major bleeding rates of 3.0% in both groups [2]. These findings were presented at the ACC.25 conference in Chicago on March 30, 2025, and simultaneously published in The Lancet, marking a significant milestone in post-PCI care protocols [3].
Future Implications and Research Direction
While the results are promising, researchers acknowledge certain limitations, including the study’s open-label design and its concentration in South Korean centers [2]. The research team plans to conduct further analyses to identify whether specific patient subgroups experienced different outcomes [1]. With a favorable number needed to treat of just 45 patients to prevent one adverse event, these findings provide valuable insights for selecting single antiplatelet regimens following PCI [2][alert! ‘Long-term effects beyond 2.3 years not yet studied’].