Research in context
Evidence before this study
Numerous studies have investigated the benefits and risks of aspirin in the acute management of cardiovascular events and in longer-term secondary prevention among people with cardiovascular disease. Fewer large-scale trials were done in the primary prevention of cardiovascular disease before the design of the ARRIVE trial. There remains a gap in the understanding of benefits and risks of aspirin use in patients at moderate risk of cardiovascular disease. We considered six key aspirin primary prevention studies before doing this study (the only published large-scale trials), which showed a reduction in risk of cardiovascular disease, largely due to a reduction in the risk of myocardial infarction among people treated with aspirin. Four additional studies of aspirin (81–100 mg daily) in the primary prevention setting have been published since the initial design of ARRIVE. These studies, and the meta-analyses that followed, were also considered in the implementation of ARRIVE and for the interpretation of the ARRIVE findings.
Added value of this study
Findings of the ARRIVE trial add to our understanding of the use of aspirin in primary prevention in several ways. First, the study was designed to assess the benefit of 100 mg per day of enteric-coated aspirin versus placebo in the reduction of incident myocardial infarction, stroke, and related cardiovascular conditions in people considered to be at moderate risk, with the exclusion of patients with diabetes. An additional objective of ARRIVE was to assess the safety and tolerability of aspirin in these patients in the setting of decreasing population-wide cardiovascular risk. Finally, ARRIVE assessed the role of aspirin with a background of modern preventive and therapeutic strategies. The findings of ARRIVE are generally consistent with the collective results of the previous primary prevention studies.
Implications of all the available evidence
While ARRIVE sought to add relevant information about the cardiovascular benefits and bleeding risks of aspirin among people at moderate cardiovascular risk, it shows some of the challenges of doing long-term prevention studies in the current era. Findings from ARRIVE are generally consistent with many other studies that tended to show aspirin's ability to lower the risk of first non-fatal myocardial infarction without affecting the risk of total stroke. With respect to safety, as expected, rates of gastrointestinal bleeding events and some other minor bleeding events were higher in the aspirin treatment group, but there was no difference in the incidence of fatal events. The use of aspirin remains a decision that should involve a thoughtful discussion between a clinician and a patient, given the need to weigh the cardiovascular as well as possible cancer prevention benefits against the bleeding risks, patient preferences, cost, and other factors. ARRIVE contributes useful information in relation to the efficacy and safety of aspirin in the intermediate term. The ARRIVE study adds additional relevant data to the body of evidence that can help the clinician with the decision as to when to use aspirin. The ARRIVE data must be interpreted in the context of other studies, which have tended to demonstrate a reduction primarily in myocardial infarction, but less of an effect on total stroke (including both ischaemic and haemorrhagic stroke). The overall decision to use aspirin should be based on individual patient–physician discussion.