Vol.:(0123456789) 1 3 Internal and Emergency Medicine https://doi.org/10.1007/s11739-019-02191-4 IM - REVIEW Aspirin in primary prevention: the triumph of clinical judgement over complex equations Francesca Santilli 1  · Paola Simeone 1 Received: 22 June 2019 / Accepted: 4 September 2019 © Società Italiana di Medicina Interna (SIMI) 2019 Abstract Aspirin, in 2017, has celebrated its 120th birthday. The efcacy 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 beneft 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 beneft 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 efort 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 diferent immediate and long-term impact of diverse outcomes on health, the dynamic nature over time of the beneft/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 fnal confrmation by the long-term follow-up of the latest trials specifcally designed to assess this endpoint, with the expectation to subvert the delicate beneft/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. Keywords Aspirin · Primary prevention · Clinical trials · Cancer · Aspirin responsiveness Abbreviations COX-1 Cyclooxygenase TXA 2 Thromboxane A 2 MI Myocardial infarction PGI 2 Prostacyclin NNT Number needed to treat NNH Number needed to harm ASCVD Atherosclerotic cardiovascular disease CRC Colon-rectal cancer DM Diabetes mellitus NSAIDs Nonsteroidal antiinfammatory drugs ACS Acute coronary syndrome GI Gastrointestinal RCT Randomized controlled trial EMT Epithelial mesenchymal transition Introduction Aspirin, in 2017, has celebrated its 120th birthday. Aspi- rin, used in preventing cardiovascular and cerebrovascular diseases, is the most widely prescribed drug all over the world [1]. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back more than 3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome [1]. Bayer chemist Felix Hofmann synthesized aspirin in 1897, and 70 years later, the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production [1]. * Francesca Santilli francesca.santilli@unich.it 1 Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), “G. D’Annunzio” University Foundation School of Medicine, Via Luigi Polacchi, 66013 Chieti, Italy