Abstract
BackgroundEvidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease.MethodsWe investigated the risk of CRC among new-users of low-dose aspirin (75–300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case–control analysis. Two cohorts (N = 170,336 each) aged 40–89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified ‘as-treated’ independent from baseline exposure status to account for changes in exposure during follow-up.ResultsCurrent users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60–0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63–0·79) and 0.60 (0.53–0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66–1.33) for Dukes Stage A CRC, 0.54 (0.42–0.68) for Dukes B, 0.71 (0.56–0.91) for Dukes C, and 0.60 (0.48–0.74) for Dukes D. After 5 years’ therapy, the RR for Dukes Stage A CRC was 0.53 (0.24–1.19).ConclusionsPatients starting low-dose aspirin therapy have a reduced risk of Stages B–D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years’ therapy.
Highlights
Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC)
Using a United Kingdom (UK) primary care database of electronic medical records (EMRs), we carried out a cohort study with nested case–control analysis to evaluate the association between use of low-dose aspirin and risk of incident CRC, both overall and by aspirin dose, duration of use and indication
We hypothesized that the strength of association between low-dose aspirin and CRC would vary by Dukes stage at diagnosis
Summary
Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. Long-term (up to 20 years) follow-up of cardiovascular trials have demonstrated, in post hoc analyses, that patients randomized to daily low-dose aspirin (75–300 mg) have a reduced risk of CRC incidence and mortality after a delay of several years [2]. The hypothesis that aspirin has a chemopreventive effect early in the adenoma sequence in CRC development is consistent with this latency period, and is supported by findings from randomized controlled trials (RCTs) showing daily low-dose aspirin (81–325 mg) reduces colorectal adenoma recurrence in average/highrisk populations [3]. Aspirin may have an inhibitory effect on the growth and spread of tumours as well as on their initial development, and this effect could be explored further in realworld patients by the evaluation of low-dose aspirin on the risk of different stage CRC in clinical practice
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