Balance of Benefits and RisksWhile the balance of vascular benefits and risk of major GI bleeding due to aspirin is clearly favourable in patients with established coronary or cerebrovascular disease and at average haemorrhagic risk ( Table 3), such a balance is substantially uncertain in middle-aged people without symptomatic vascular disease, and will depend on the estimated annual risk of vascular vs. bleeding complications in the individual patient.
It is important to consider that the two risks may track together as a function of common determinants ( Figure 5 ).
It has been argued that the size of the absolute benefit of aspirin could be halved by the cardiovascular risk reduction associated with the use of other effective preventive strategies (e.g. statin therapy), virtually abolishing the difference between the number of vascular events avoided and major bleeds caused by aspirin ( Figure 5 ). However, the same halving of the absolute excess of bleeding complications could be expected from the use of effective cytoprotective strategies (e.g. H. pylori eradication, proton pump inhibition). 
The HEAT trial ( HelicobacterEradication Aspirin Trial) is currently testing the hypothesis that a 1-week course of H. pylori eradication in 10 000 H. pylori -positive patients using low-dose aspirin will halve the incidence of subsequent adjudicated peptic-ulcer bleeding that results in hospitalization.
Moreover, the recent demonstration that low-dose aspirin reduces deaths due to cancer and overall incidence during trial follow-up suggests that there is a modest overall short-term benefit in primary prevention after taking into account all of the major outcomes.  Taken with the previously reported reductions in post-trial cancer deaths, [55,56] the demonstration of overall benefit from aspirin in the short-term adds to the case for long-term use of aspirin for cancer prevention in middle age. 
It has been argued that even a 10% reduction in overall cancer incidence from prophylactic aspirin treatment would tilt the balance of benefits and risks, and substantially broaden the indication for treatment in populations at average risk. 
For secondary cardiovascular prevention, the net benefits of adding aspirin to other preventive measures would substantially exceed the bleeding hazards, irrespective of age and gender.[66,67]
In contrast, for many people without pre-existing vascular disease, the cardiovascular benefits of adding long-term aspirin to other, safer, forms of primary prevention (e.g. statins and antihypertensive drugs) are likely to be of similar magnitude as the hazards. 
Four ongoing primary prevention trials may help assess the benefit/risk profile of low-dose aspirin in preventing multiple outcomes (including dementia and cancer) in ~50 000 participants at somewhat higher cardiovascular risk than in the earlier trials, because of diabetes mellitus (ASCEND  and ACCEPT-D),  advanced age (ASPREE),  or a cluster of risk factors (ARRIVE). 
Hence, the currently available trial results do not seem to justify general guidelines advocating or discouraging  the routine use of aspirin in all apparently healthy individuals above a moderate level of coronary risk, unless additional long-term benefits of aspirin therapy become firmly established. 
In the meantime, clinical judgement as well as adequate knowledge of the available data may help the doctor–patient relationship in making a personalized choice after considering the different components of a complex equation that includes the patient's preferences and values.