New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case–control study in UK general practice

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.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3594-9) contains supplementary material, which is available to authorized users.

Clopidogrel and Low-Dose Aspirin, Alone or Together, Reduce Risk of Colorectal Cancer

“…First, the effect appears early over the treatment course, in agreement with a recently published study. 4 Second, our study was performed in a Mediterranean population and its preventive effect on CRC was of similar magnitude to the one observed in other populations with greater cardiovascular comorbidity, 3,4,8 which suggests that such an effect is independent from lifestyle factors. Our results also show that the chemoprotective effect was not maintained in recent or past users, a finding compatible with the interference of low-dose aspirin into the progression of cancer being a reversible effect on discontinuation.…”

“…1,2 A large number of studies have reported a protective effect of low-dose aspirin against CRC. 3,4 Based on this evidence, in 2016, the updated guidelines of the US Preventive Services Task Force (USPSTF) endorsed the use of low-dose aspirin for the prevention of cardiovascular diseases and CRC among adults aged 50 to 59 years who have a 10% or greater 10-year cardiovascular risk and no increased risk of bleeding with a life expectancy of at least 10 years. 5 For adults aged 60 to 69 years with the same clinical characteristics, the USPSTF recommended individualizing the decision to initiate treatment.…”

The effect of low-dose aspirin on colorectal cancer prevention and gastrointestinal bleeding according to bodyweight and body mass index: Analysis of UK primary care data

“…Data held includes clinical information entered as part of routine patient care, including prescriptions issued and information communicated from secondary care. Full details of our two original studies, including approval of the study protocols, have been published previously [5,12].…”

“…Low-dose aspirin is well-established in reducing the risk of ischaemic vascular events [1,2] an effect mediated through its irreversible inhibition of cyclooxygenase I (COX-1) in platelets leading to suppression of thromboxane A 2 [3]. There is mounting evidence from both randomized controlled trials (RCTs) and observational studies that low-dose aspirin protects against colorectal cancer (CRC) [4][5][6] an effect possibly also mediated by platelet inhibition, [7,8] and a factor to be considered when evaluating whether the benefits of low-dose aspirin outweigh the risk of major bleeding in specific patient populations.…”

“…We have previously published findings from two large populationbased studies evaluating the association between low-dose aspirin (75-300 mg/day) and risk of CRC/upper gastrointestinal bleeding (UGIB) [5,12]. These studies used a matched cohort study design to minimize bias from differences at the start of follow-up between low-dose aspirin users and non-users that are difficult to control for, and a nested case-control analysis to accurately analyze recent low-dose aspirin exposure.…”