ArticlesEffect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials
Introduction
Cancer is the second most common cause of death worldwide and 5 million new cases are diagnosed each year in Europe and the USA alone.1, 2, 3 There has been evidence from animal studies and from observational studies in humans that daily aspirin might be effective in preventing several common cancers,4, 5, 6, 7, 8 which has recently been confirmed by follow-up of patients originally included in randomised trials of daily aspirin versus control in the prevention of vascular events.9, 10, 11, 12 Allocation to aspirin in these trials resulted in a 40% reduction in cancer deaths from 5 years onwards,12 with sustained reductions in deaths due to certain cancers at 20-year follow-up.9, 10, 11
These recent reports of randomised trials suggest that aspirin might also have short-term effects on outcome in patients who develop cancer while on treatment. First, the effect of aspirin on death due to cancer was greater than the apparent effect on incidence of cancer.12 Second, the reduction in mortality due to some cancers occurred within 2–3 years after randomisation and seemed too quick to be accounted for by an effect only on carcinogenesis or early cancer growth.12 Third, there was a reduction in deaths due to metastatic cancer with unknown primary.12 We therefore hypothesised that these shorter-term effects of aspirin could be due to the prevention of distant metastasis, consistent with experimental evidence in animals that platelets play an important part in blood-borne metastases,13, 14, 15, 16 which are reduced by aspirin,15, 16, 17, 18, 19 and with observational studies in humans that showed that aspirin use is associated with reduced distant metastasis and with decreased rates of recurrence in patients with common adenocarcinomas.7, 20, 21, 22, 23, 24 Since the results in animal studies might not apply to humans and because the observational studies are subject to several potential biases, we studied metastasis at initial diagnosis and during subsequent follow-up in all participants with a new diagnosis of cancer in all five large completed randomised trials of aspirin versus control in prevention of vascular events in the UK.25, 26, 27, 28, 29
Section snippets
Trials
Recent literature searches identified all randomised trials of aspirin (any dose) versus no aspirin in the absence of another antiplatelet agent, or aspirin (any dose) versus no aspirin in the presence of another antithrombotic agent (if balanced in the aspirin and no aspirin groups) in prevention of vascular events.11, 12 We restricted inclusion to trials done in the UK because of the availability of reliable and well validated centralised death certification and cancer registration to ensure
Trials
Of the five eligible randomised trials of aspirin versus control (appendix p 1), two had been done in primary prevention of vascular disease,25, 27 one in secondary prevention after recent vascular events,26 and two in groups with asymptomatic peripheral arterial disease (one in patients with diabetes;28 one in individuals with low ankle brachial index on screening29). Among the 17 285 participants in the five trials, there were 1101 incident cancers and 563 deaths due to incident cancer during
Discussion
Daily aspirin reduces the incidence of colorectal cancer after a delay of 8–10 years9, 10 and reduces mortality due to several other adenocarcinomas after a similar delay,11 consistent with the latency expected before the clinical manifestation of an effect on early carcinogenesis. However, the accompanying analysis of data from 51 trials of aspirin versus control showed that aspirin reduced mortality from all cancer after only 5 years, with even earlier reductions in deaths due to colorectal
References (41)
- et al.
Estimates of the cancer incidence and mortality in Europe in 2006
Ann Oncol
(2007) - et al.
Aspirin, salicylates, and cancer
Lancet
(2009) - et al.
Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement
Lancet Oncol
(2009) - et al.
Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies
Lancet
(2007) - et al.
Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials
Lancet
(2010) - 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) - et al.
The platelet contribution to cancer progression
J Thromb Haemostat
(2011) - et al.
Anti-metastatic effect of aspirin
Lancet
(1972) - et al.
Aspirin dose and duration of use and risk of colorectal cancer in men
Gastroenterology
(2008) - et al.
Cigarette smoking and risk of pulmonary metastasis from breast cancer
Chest
(2001)