Aspirin’s antithrombotic effects have a long-established place in the prevention of cardiovascular disease (CVD), and its traditional use as a core therapy for secondary prevention of CVD is well recognized. However, with the advent of newer antiplatelet agents and an increasing understanding of aspirin’s bleeding risks, its role across the full spectrum of modern CVD prevention has become less certain. As a consequence, recent trials have begun investigating aspirin-free strategies in secondary prevention. For example, a contemporary metanalysis of trials that assessed P2Y inhibitor monotherapy versus prolonged (≥ 12 months) dual antiplatelet therapy (which includes aspirin) after percutaneous coronary intervention reported a lower risk of major bleeding and no increase in stent thrombosis, all-cause mortality, myocardial infarction (MI), or stroke in the P2Y monotherapy group. In contrast to secondary prevention, aspirin’s role in primary prevention has always been more controversial. While historical trials reported a reduction in MI and stroke, more contemporary trials have suggested diminishing benefit for aspirin in this setting, with no reduction in hard outcomes, and some primary prevention trials have even indicated a potential for harm. In this review, we discuss how changing population demographics, enhanced control of lipids and blood pressure, changes in the definition of outcomes like MI, evolution of aspirin formulations, and updated clinical practice guidelines have all impacted the use of aspirin for primary and secondary CVD prevention.
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