SRK Seshasai, S Wijersuiya, R Sivakumaran, S Nethercott, S Erqou, N Sattar, KK Ray [NNT = Numbers needed to treat: this is the number of persons who would have to take aspirin for 6 years in order to prevent 1 event]. [NNH = Numbers needed to harm: this is the number of persons taking aspirin for 6 years in order to cause harm to 1 person]. KEY POINTS FROM THIS STUDY: 1) The net benefit of aspirin in prevention of CVD and nonvascular events remains unclear. These authors assessed the impact (and safety) of aspirin on vascular and nonvascular outcomes in primary prevention. 2) The authors used 9 good-quality randomized placebo-controlled trials of aspirin for primary prevention of CVD that included 102,621 participants who were followed-up for 6 years, making approximately 700,000 person-years. 3) These authors compared rates of any statistically meaningful associations (CVD or nonfatal MI) with rates of bleeding. 4) Nontrivial bleeding was defined as fatal bleeding; cerebrovascular or retinal bleeding; bleeding from hollow viscus; bleeding requiring hospitalization and/or transfusion; or study-defined major bleeding regardless of source. 5) This meta-analysis is the largest evidence to date regarding the wider effects of aspirin treatment in primary prevention. 6) During a follow-up of 6.0 years involving over 100,000 participants, aspirin treatment: A)) Reduced total CVD events by 10%, but with a NNT of 120 [120 people had to take aspirin for 6 years to prevent 1 CVD event]. The NNT to avoid 1 CVD event over 6 years was 120. B)) Reduced nonfatal MI by 20%, but with a NNT of 162 [162 people had to take aspirin for 6 years to prevent 1 nonfatal MI]. The NNT to avoid 1 nonfatal MI event over 6 years was 162. C)) There was no significant reduction in CVD death or cancer mortality, and there was increased risk of nontrivial bleeding events by 31% (NNH was 73). At least 1 nontrivial bleeding event was caused for every 73 persons treated with aspirin for approximately 6 years. 2 D)) There was a 70% excess risk of total bleeding events and a higher than 30% excess risk of nontrivial bleeding events in people receiving aspirin. E)) The NNT to avoid nonvascular death over 6 years was 292. F)) The NNT to avoid cancer death over 6 years was 247. 7) The net benefits due to aspirin treatment were offset by increased rates of nontrivial bleeding. 8) Aspirin benefits are considerably offset by an elevated risk of bleeding (NNT for nonfatal MI of 162 vs NNH for nontrivial bleed of 73). 9) The findings reported herein do not suggest a protective role for aspirin against cancer mortality in people at low-to-moderate risk for CVD events. 10) The principal cardiovascular effect of aspirin in primary prevention is on nonfatal MI with no real benefit with regard to fatal MI, stroke, or CVD death. 11) The results suggest an increased risk of nontrivial bleeding in individuals receiving daily (vs alternate day) aspirin treatment, with a particularly unfavorable risk to benefit ratio for individuals at lower baseline CVD risk. 12) Both patients and physicians should carefully consider the relative merits of daily aspirin treatment in primary prevention. 13) Our analysis also showed that aspirin was no better than placebo for reducing nonfatal MI events in trials published after 2000. 14) Aspirin may add little extra value to other CVD risk reduction strategies, especially in low-risk individuals. 15) Aspirin may be associated with net harm owing to increased potential for bleeding. 16) Based on our findings of a marginal benefit on nonfatal MI, a nonsignificant effect on cancer death, and a significantly increased risk of clinically relevant bleeding, it is perhaps timely to reappraise existing guidelines for aspirin use in primary prevention. 17) A reappraisal of current guidelines appears to be warranted, particularly in countries where a large number of otherwise healthy adults are prescribed aspirin, since a significant proportion of them may develop bleeding complications.