A commonly prescribed drug could be more effective than aspirin for long-term heart disease prevention.
Analysis of nearly 29,000 patients with coronary artery disease (CAD) suggests the blood thinner clopidogrel is more effective than aspirin in preventing serious heart and stroke events—without increasing the risk of major bleeding.
This challenges the long-standing recommendation of aspirin as the default treatment for secondary prevention in CAD patients, according to international research.
“This is the first definitive demonstration that clopidogrel is more effective and similarly safe than aspirin in patients with CAD. We have had some prior trials suggesting this but none had a definitive power to prove this,” study author and cardiologist professor Marco Valgimigli of the University of Italian, Switzerland, told Newsweek.
Man looking at white medication box.
Man looking at white medication box.
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CAD, characterized by narrowed heart arteries, typically requires lifelong treatment to prevent heart attacks, stroke and cardiovascular death.
Aspirin is traditionally been prescribed indefinitely for patients with CAD, but the evidence supporting its long-term benefits and safety has been limited, according to the study.
The new analysis of seven clinical trials found that patients taking clopidogrel had a 14 percent lower risk of major adverse cardiovascular or cerebrovascular events (including heart attack, stroke or cardiovascular death) compared to those taking aspirin.
Crucially, the rates of major bleeding were similar between the two drugs, “dispelling concerns” that clopidogrel might lead to more bleeding complications.
“There is a widespread perception in the community, especially surgeons, that clopidogrel is associated with greater bleeding risk than aspirin,” explained Valgimigli.
The study drew from “diverse patient groups,” including those who had undergone procedures like stent placement or had experienced acute coronary syndrome—analyzing various subgroups allowed the team to ensure that the findings applied broadly.
A key finding was that even patients who might respond less well to clopidogrel due to genetic or clinical factors still benefited from its use over aspirin.
This suggests clopidogrel should be considered the preferred long-term antiplatelet medication for patients with established coronary artery disease.
Because both medications are widely available, the findings have the potential to influence clinical guidelines worldwide and improve patient outcomes, the authors said.
“Clopidogrel leads to roughly 20 percent risk reduction of MI [myocardial infarction, or heart attack] and stroke. Taking into account the long-term treatment duration, this could translate into a very low number needed to treat to avoid one of these events compared with aspirin,” said Valgimigli.
The researchers concluded that their study adds to the evidence that clopidogrel alone is superior to aspirin in the prevention of so-called “Major Adverse Cardiac and Cerebrovascular Events” and also supports the use of clopidogrel over aspirin for secondary prevention in patients with established CAD.
Further investigation—including assessment of the the cost-effectiveness of clopidogrel, as well as broader population studies—will be needed to support any future changes in treatment standards.
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Reference
Valgimigli, M., Choi, K. H., Giacoppo, D., Gragnano, F., Kimura, T., Watanabe, H., Kim, H.-S., Kang, J., Park, K. W., Pettersen, A.-Å., Woodward, M., Bhatt, D. L., Calabrò, P., Angiolillo, D. J., Mehran, R., Song, Y. B., & Hahn, J.-Y. (2025). Clopidogrel versus aspirin for secondary prevention of coronary artery disease: A systematic review and individual patient data meta-analysis. The Lancet. https://doi.org/10.1016/S0140-6736(25)01562-4