Clopidogrel is a prodrug that is activated in the liver by the CYP2C19 enzyme, and genetic variability affects its clinical efficacy. In 2024, the National Institute for Health and Care in the United Kingdom recommended CYP2C19 genotyping in patients with acute transient ischemic attack and stroke before treatment. Marco Valgimigli and colleagues published a systematic review and meta-analysis comparing clopidogrel with aspirin for the secondary prevention of coronary artery disease. This meta-analysis included three studies with a total of 7081 patients after percutaneous coronary intervention with acute coronary syndrome, of whom 4260 received aspirin and 2821 clopidogrel as monotherapy after dual antiplatelet therapy. Clopidogrel was associated with a 28% reduction in the risk of major adverse cardiovascular events compared to aspirin (hazard ratio 0.72; 95% CI: 0.54–0.98). There was no significant difference in the risk of clinically relevant bleeding (hazard ratio 0.92; 95% CI: 0.68–1.24). The authors emphasize that CYP2C19 genetic variation is less important over time than in the acute phase. The results are hypothetical and require further large randomized controlled trials.