Aspirin in primary prevention: the triumph of clinical judgement over complex equations

Aspirin, in 2017, has celebrated its 120th birthday. The efficacy and safety of low-dose aspirin in secondary prevention of cardiovascular disease is well supported by many studies, instead in primary prevention it remains controversial, especially in the aftermath of the publication in 2018 of three novel primary prevention randomized clinical trials, showing that the benefit of low-dose aspirin, although additive to that of statin, is counterbalanced by an excess of (mainly gastrointestinal) bleeding events. The signal for a net benefit seems to be even more controversial in the elderly starting aspirin after the age of 70 years. While international guidelines have promptly downgraded their recommendations to more conservative indications, the practicing clinician is called to make the effort to individualize the treatment, after careful evaluation of the haemorrhagic risk vis-a-vis the risk to develop, in the mid-term and long-term follow-up, major cardiovascular events or cancer. This is a particularly complex task, given the different immediate and long-term impact of diverse outcomes on health, the dynamic nature over time of the benefit/risk balance, prompting periodic re-assessments of its indication, and the interindividual variability in aspirin response. The chemopreventive properties of aspirin, anticipated by a large body of epidemiological and mechanistic evidence, are awaiting their final confirmation by the long-term follow-up of the latest trials specifically designed to assess this endpoint, with the expectation to subvert the delicate benefit/risk balance of aspirin in primary prevention. This review is intended to provide an interpretation of past and current evidence to guide clinical decision making on the contemporary patient.