Whilst the benefit of aspirin for cardiovascular disease (CVD) risk reduction remains well-established in people who have experienced a prior vascular event¹, the benefit seems more modest in those who have not yet experienced a CVD event². In fact, in the latter group of individuals, pooled data from multiple randomised controlled trials suggest no benefit with regard to CVD/total mortality, and an excess risk of major bleeding which may offset any benefits with regard to vascular risk reduction³.

Nonetheless, in recent years there has been a major surge in our interest surrounding the role of aspirin in primary and secondary prevention, in part due to its purported benefits in reducing the risk of cancer (primarily gastro-intestinal, mainly proximal colonic^4-7). However, despite compelling evidence, the beneficial effects of aspirin for the prevention of cancer (both de novo and metastatic) may be somewhat overstated because: (i) pooled analyses evaluating this association had combined both primary and secondary prevention trials of aspirin (and where data were available for the latter, large studies of alternate-day aspirin use have been excluded); (ii) trials included in these meta-analyses seldom pre-specified cancer incidence/mortality as their primary endpoint, and were conducted in an era where the diagnostic and treatment strategies for cancer were different to contemporary methods; (iii) despite large sample sizes and prolonged follow-up times in these meta-analyses, the overall event rates for cancer were small, and lastly (iv) the beneficial effect on cancers was generally evident after 5 years of follow-up – i.e., after conclusion of the main trial per se. Therefore, the observed (beneficial) associations may have been due to a complex interplay between various biological factors involved in oncogenesis, and methodological factors such as participant attrition and cross-over during post-trial follow-up.

Hence, the most robust defence in favour of the wider benefits of aspirin, especially in primary prevention, would only be through bespoke clinical trials involving large sample size(s) and with a very long active treatment/randomisation phase (e.g. 10 years), and taking into account the risks incumbent in the process.

References:

1. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324: 71–86
2. Antithrombotic Trialists’ (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373: 1849–60
3. Seshasai SR, Wijesuriya S, Sivakumaran R et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172:209-16
4. Rothwell PM, Wilson M, Elwin CE et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376:1741-50
5. Rothwell PM, Fowkes FG, Belch JF et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377:31-41
6. Rothwell PM, Price JF, Fowkes FG et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602-12
7. Rothwell PM, Wilson M, Price JF et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591-601