Aspirin in Primary Prevention: Looking for Those Who Enjoy It

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.