Aspirin vs Clopidogrel: Scoping Review with ☸SAIMSARA

To synthesize the evidence comparing the efficacy and safety of aspirin and clopidogrel across diverse clinical settings, including coronary artery disease (CAD), ischemic stroke, peripheral artery disease (PAD), and perioperative management. The review utilises 2319 original studies with 9103381 total participants (topic deduplicated ΣN). The mapped evidence suggests that clopidogrel monotherapy is a prominent long-term alternative to aspirin, with the clearest advantage appearing after percutaneous coronary intervention and in broad symptomatic atherosclerotic disease, where reported hazard ratios ranged from 0.71 to 0.86 in post-percutaneous coronary intervention maintenance studies and CAPRIE reported an annual risk of 5.32% versus 5.83%, corresponding to an 8.7% relative risk reduction. This signal was not uniform across all settings: stroke cohorts were mixed, and the apparent benefit of clopidogrel was repeatedly modified by high on-treatment platelet reactivity and CYP2C19 loss-of-function status. Safety patterns were similarly context dependent, with clopidogrel often appearing less injurious to the upper gastrointestinal tract in general-risk settings, yet aspirin plus esomeprazole outperforming clopidogrel alone after prior aspirin-related ulcer bleeding, and perioperative bleeding concerns more often favoring aspirin when procedures cannot be delayed. Clinically, the evidence map supports a role for clopidogrel as a preferred single antiplatelet option after the dual antiplatelet phase following percutaneous coronary intervention, while also highlighting the need to individualize treatment according to gastrointestinal history, surgical plans, and likely clopidogrel responsiveness. Future research should prioritize indication-specific prospective comparisons, especially in heterogeneous stroke populations and very elderly patients, with integrated genotype-guided strategies to clarify who benefits most from aspirin versus clopidogrel.