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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: 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.We 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.Current 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).Patients 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.

SUBMITTER: Garcia Rodriguez LA

PROVIDER: S-EPMC5590216 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

García Rodríguez Luis A LA Soriano-Gabarró Montse M Bromley Susan S Lanas Angel A Cea Soriano Lucía L

BMC cancer 20170907 1

<h4>Background</h4>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.<h4>Methods</h4>We 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 ...[more]

PMID: 28882113

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Project description:ImportancePopulation-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC).ObjectiveTo evaluate the association between duration and recency of low-dose aspirin use and CRC risk.Design, setting, and participantsThis nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin. Data were collected from Taiwan National Health Insurance and Taiwan Cancer Registry from 2000 through 2015. CRC cases were age- and sex-matched in a 1:4 ratio with individuals in a control group, identified from a cohort of individuals who used and did not use aspirin through risk-set sampling. Data analysis was conducted from June 2018 to July 2019.ExposuresLow-dose aspirin use was defined as receiving less than 150 mg per day, whereas 100 mg/d was most commonly used. Based on duration and recency of low-dose aspirin use between cohort entry (initiation date of low-dose aspirin for aspirin use group or randomly assigned date for those who did not use aspirin) and index date (CRC diagnosis date for individuals in the case group and the diagnosis date for the 4 corresponding matched individuals in the control group), the 3 following mutually exclusive exposure groups served as the basis for analysis: (1) long-term current low-dose aspirin use, (2) episodic low-dose aspirin use, and (3) no low-dose aspirin use (the reference group).Main outcomes and measuresCRC risk among the 3 exposure groups.ResultsAmong 4 710 504 individuals (2 747 830 [51.7%] men; median [interquartile range] age at cohort entry in initiator group, 61 [52-71] years; median [interquartile range] age at cohort entry in nonuse group, 59 [51-68] years), 79 095 CRC cases (1.7% of study cohort) were identified. Compared with no low-dose aspirin use, the adjusted odds ratio (OR) for long-term current low-dose aspirin use and CRC risk was 0.89 (95% CI, 0.85-0.93); for episodic use, 0.88 (95% CI, 0.86-0.89). Adjusted ORs of 0.69 (95% CI, 0.63-0.76) and 0.64 (95% CI, 0.61-0.67) were observed for long-term current use and episodic low-dose aspirin use within the subcohort of individuals who initiated low-dose aspirin between age 40 and 59 years.Conclusions and relevanceIn this study, low-dose aspirin use was associated with 11% lower CRC risk in an East Asian population, and this association was larger when low-dose aspirin use started before age 60 years.

Project description:ObjectivesHypotension is of particular relevance for patients with heart failure (HF), since almost all HF drugs cause lowering of blood pressure (BP) and it is associated with a poor prognosis. We aimed to investigate hypotension incidence and risk factors in patients with incident HF in the UK.DesignRetrospective cohort study including nested case-control analyses.SettingThe Health Improvement Network UK primary care database.Participants18 677 adult patients with incident HF during 2000-2005 were followed and cases of hypotension (systolic BP ≤90 mm Hg) were identified. Controls were age-matched, sex-matched and date-matched to cases (1:2).Primary and secondary outcome measuresWe estimated hypotension incidence in the full study population and relevant subgroups (eg, sex and age). Potential risk factors for hypotension overall and for multiple versus single hypotensive episodes were evaluated using conditional logistic regression and unconditional regression models, respectively.ResultsDuring a mean follow-up of 3.31 years, 2565 patients (13.7%) developed hypotension. The incidence of hypotension was 3.17 cases per 100 patient years (95% confidence interval (CI): 3.05-3.30), and was markedly increased in women aged 18-39 years (n=32; 17.72 cases per 100 patient-years; 95% CI: 9.69-29.73). Hypotension risk factors included high healthcare utilisation (proxy measure for HF severity and general comorbidity; eg, ≥10 primary care physician visits versus none, odds ratio (OR): 2.29; 95% CI: 1.34-3.90), previous hypotensive episodes (OR: 2.32; 95% CI: 1.84-2.92), renal failure and use of aldosterone antagonists, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Risk factors identified for hypotension generally overlapped with those for multiple versus single hypotensive episodes.ConclusionsHypotension occurs frequently in patients with incident HF. Our findings may help identify patients most likely to benefit from close BP monitoring. The increased incidence of hypotension in young women with HF requires investigation.

Dataset Information

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

Publications

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

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