Clopidogrel Outperforms Aspirin in Long-term Cardiovascular Event Prevention

A recent analysis presented at the European Society of Cardiology Congress on August 31, 2025, and published in The Lancet, indicates that clopidogrel is more effective than aspirin in preventing major cardiovascular events among patients with coronary artery disease (CAD). The study, which pooled data from nearly 29,000 participants across seven trials, found that clopidogrel reduced the risk of heart attacks, strokes, and cardiovascular deaths by 14% compared to aspirin over an average follow-up of 5.5 years. Notably, the analysis reported no significant difference in bleeding risks between the two medications, even among patients with genetic or clinical factors that might reduce clopidogrel efficacy. These findings suggest that clopidogrel could be considered the preferred long-term antiplatelet medication for patients with established CAD.

Coronary artery disease remains a leading cause of morbidity and mortality worldwide, characterized by the narrowing or blockage of coronary arteries due to plaque buildup. Antiplatelet therapy plays a crucial role in preventing thrombotic events in CAD patients. Traditionally, aspirin has been the cornerstone of such therapy due to its efficacy in inhibiting platelet aggregation. However, the emergence of P2Y12 inhibitors like clopidogrel has provided alternative options.

The recent meta-analysis presented at the ESC Congress and published in The Lancet analyzed data from seven randomized trials involving nearly 29,000 CAD patients. The key findings include:

• Efficacy: Clopidogrel reduced the risk of major adverse cardiovascular or cerebrovascular events by 14% compared to aspirin over an average follow-up of 5.5 years.

• Safety: There was no significant difference in major bleeding risks between the two drugs.

• Genetic Factors: Benefits of clopidogrel were observed even among patients with genetic or clinical factors that might reduce its efficacy.

These results suggest that clopidogrel could be considered the preferred long-term antiplatelet medication for patients with established CAD.

Supporting evidence from previous studies aligns with these findings. The SMART-CHOICE 3 Trial, presented at the American College of Cardiology’s Annual Scientific Session in March 2025, found that high-risk patients post-percutaneous coronary intervention (PCI) experienced significantly better outcomes with clopidogrel than aspirin as long-term antiplatelet therapy. After a median follow-up of over two years, clopidogrel users were 29% less likely to experience all-cause death, heart attack, or stroke. No significant difference in major bleeding rates was observed.

Similarly, the HOST-EXAM Trial in May 2021 demonstrated that clopidogrel outperformed aspirin in long-term maintenance therapy for patients who had no adverse events after one year of dual antiplatelet therapy following coronary stenting. Over two years, clopidogrel resulted in a 30% reduction in deaths, heart attacks, strokes, or major bleeding events compared to aspirin.

The consistent evidence favoring clopidogrel over aspirin in various patient populations suggests a potential shift in clinical guidelines. Healthcare providers may consider prescribing clopidogrel as the preferred long-term antiplatelet therapy for CAD patients, especially those at high risk for recurrent ischemic events. However, individual patient factors, including genetic predispositions affecting drug metabolism, should be considered.

Historically, clopidogrel was significantly more expensive than aspirin. However, with the expiration of patent protection, generic versions have become more affordable, enhancing its cost-effectiveness. A network meta-analysis highlighted that clopidogrel monotherapy reduces bleeding events compared to other antithrombotic drugs, making it a viable option for long-term treatment in CAD patients.

The recent meta-analysis, along with supporting studies, underscores the superior efficacy and comparable safety profile of clopidogrel over aspirin in preventing major cardiovascular events in CAD patients. These findings may prompt a reevaluation of current clinical guidelines, potentially positioning clopidogrel as the preferred long-term antiplatelet therapy in this patient population.