Prediagnostic use of low-dose aspirin and risk of incident metastasis and all-cause mortality among patients with colorectal cancer.
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ABSTRACT: Aims
Previous studies suggest that the use of low-dose aspirin before a colorectal cancer (CRC) diagnosis may be associated with a decreased risk of CRC progression. Data supporting this association, however, have been inconsistent. We evaluate whether the use of prediagnostic low-dose aspirin is associated with a lower risk of metastases and all-cause mortality in CRC patients.Methods
Using a large Italian population-based primary care database, we identified a cohort of 7478 patients newly diagnosed with nonmetastatic CRC between 2000 and 2013. Use of prediagnostic low-dose aspirin was compared with no use of low-dose aspirin. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of incident metastasis and of all-cause mortality associated with prediagnostic low-dose aspirin use, both overall and by duration of use.Results
There were 314 incident metastatic events and 2189 deaths during a mean follow-up time of 4.4 and 4.7 years, respectively. Overall prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis (HR 0.88; 95% CI 0.63-1.22) or all-cause mortality (HR 1.09; 95% CI 0.96-1.22) in CRC patients. Cumulative duration of aspirin use was not associated with a decreased risk of incident metastasis (P-trend = .22) or all-cause mortality (P-trend = .38). These findings remained consistent in sensitivity analyses.Conclusion
In this real-world, population-based study, the prediagnostic use of low-dose aspirin was not associated with a decreased risk of incident metastasis or all-cause mortality in CRC patients.
SUBMITTER: Giorli G
PROVIDER: S-EPMC7576616 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC7677757 | biostudies-literature
Project description:BACKGROUND:Many studies have suggested that the regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, has a protective effect and survival benefit on colorectal cancer (CRC). However, recent data suggest that CRCs have different responses to NSAIDs depending on the timing of NSAID initiation, duration of NSAID use, and molecular characteristics of the tumor. The aim of this study was to evaluate the effect of long-term prediagnostic aspirin use on the prognosis of stage III CRC. METHODS:From 2007 to 2009, patients who were diagnosed with stage III CRC were recruited, and their medical records were retrospectively analyzed. Patients were divided into prediagnostic aspirin users (who used aspirin for more than three months continuously before CRC diagnosis) and non-users (who did not use of aspirin and NSAIDs). The two groups were compared in terms of recurrence, cancer-specific mortality, disease-free survival (DFS), and cancer-specific survival. In an experimental study, three CRC cell lines (Caco2, SW480, and DLD-1) were pretreated with aspirin (1 mM) for four days or 28 days to make aspirin-resistant cells, treated with 5-fluorouracil (5-FU; 2 µM), and apoptosis was measured with flow cytometry using Annexin-V and propidium iodide double staining. RESULTS:Compared with the aspirin non-users (N=565), the prediagnostic aspirin users (N=121) were not different in terms of baseline characteristics including tumor characteristics, except for comorbidities and diabetes medication and statin use, which were higher in the prediagnostic aspirin users. Recurrence and cancer-specific mortality in stage III CRC were significantly higher in prediagnostic aspirin users than non-users (46.7% vs. 32.3%, P=0.003 and 32.2% vs. 19.8%, P=0.003, respectively). Survival analysis using Cox proportional hazards modeling demonstrated that DFS was significantly worse in prediagnostic aspirin users than non-users (HR, 1.525 (1.018-2.286); P=0.041). In cell line experiments, long-term aspirin pretreatment induced an increase in 5-FU-induced apoptosis in SW480 cells compared with control treatment without aspirin pretreatment. However, Caco2 cells showed a significant decrease of apoptosis in the same experiments and no change in DLD1 cells. CONCLUSION:Prediagnostic long-term aspirin use in stage III CRC could be a negative prognostic factor depending on the characteristics of the CRC.
| S-EPMC4612965 | biostudies-literature
Project description:ObjectiveTo examine the association between cardioprotective use of low-dose aspirin and the risk of recurrent gout attacks among gout patients.MethodsWe conducted an online case-crossover study of individuals with gout over 1 year. The following information was obtained during gout attacks: the onset dates, symptoms and signs, medications, and exposure to potential risk factors, including daily aspirin use and dosage, during the 2-day hazard period prior to the gout attacks. The same exposure information was also obtained over 2-day control periods.ResultsOf the 724 participants analysed, 40.5% took aspirin ≤325 mg/day during either a hazard or a control period. Compared with no aspirin use, the adjusted OR of gout attacks increased by 81% (OR=1.81, 95% CI 1.30 to 2.51) for ≤325 mg/day of aspirin use on two consecutive days. The corresponding ORs were stronger with lower doses (eg, OR=1.91 for ≤100 mg, 95% CI 1.32 to 2.85). These associations persisted across subgroups by sex, age, body mass index categories and renal insufficiency status. Concomitant use of allopurinol nullified the detrimental effect of aspirin.ConclusionsOur findings suggest that the use of low-dose aspirin on two consecutive days is associated with an increased risk of recurrent gout attacks. Recommended serum urate monitoring with concomitant use and dose adjustment of a urate-lowering therapy among patients with gout may be especially important to help avoid the risk of gout attacks associated with low-dose aspirin.
| S-EPMC3902644 | biostudies-literature
Project description:BackgroundAspirin has been proposed as a novel adjuvant agent in colorectal cancer (CRC). Six observational studies have reported CRC-specific survival outcomes in patients using aspirin after CRC diagnosis but the results from these studies have been conflicting. Using a population-based cohort design this study aimed to assess if low-dose aspirin use after diagnosis reduced CRC-specific mortality.MethodsA cohort of 8391 patients with Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry and linked to national prescribing and death records. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific mortality were calculated using time-dependent Cox regression.ResultsThere were 1064 CRC-specific deaths after a median follow-up of 3.6 years. Post-diagnostic low-dose aspirin use was not associated with a reduction in CRC-specific mortality either before or after adjustment for confounders (adjusted HR = 1.17, 95% CI 1.00-1.36). In sensitivity analysis pre-diagnostic low-dose aspirin was also not associated with reduced CRC-specific mortality (adjusted HR = 0.96, 95% CI 0.88-1.05).ConclusionLow-dose aspirin use, either before or after diagnosis, did not prolong survival in this population-based CRC cohort.
| S-EPMC6389196 | biostudies-literature
Project description:BackgroundAspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular-dose aspirin use and gene expression profiles in ovarian tumors.MethodsRNA sequencing was performed on high-grade serous, poorly differentiated, and high-grade endometrioid ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and New England Case-Control Study (n = 92 cases for low, 153 cases for regular-dose aspirin). Linear regression identified differentially expressed genes associated with aspirin use, adjusted for birth decade and cohort. False discovery rates (FDR) were used to account for multiple testing and gene set enrichment analysis was used to identify biological pathways.ResultsNo individual genes were significantly differentially expressed in ovarian tumors in low or regular-dose aspirin users accounting for multiple comparisons. However, current versus never use of low-dose aspirin was associated with upregulation of immune pathways (e.g., allograft rejection, FDR = 5.8 × 10-10 ; interferon-gamma response, FDR = 2.0 × 10-4 ) and downregulation of estrogen response pathways (e.g., estrogen response late, FDR = 4.9 × 10-8 ). Ovarian tumors from current regular aspirin users versus never users were also associated with upregulation in interferon pathways (FDR <1.5 × 10-4 ) and downregulation of multiple extracellular matrix (ECM) architecture pathways (e.g., ECM organization, 4.7 × 10-8 ).ConclusionOur results suggest low and regular-dose aspirin may impair ovarian tumorigenesis in part via enhancing adaptive immune response and decreasing metastatic potential supporting the likely differential effects on ovarian carcinogenesis and progression by dose of aspirin.
| S-EPMC10523980 | biostudies-literature
Project description:To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.
| S-EPMC7812246 | biostudies-literature
Project description:ObjectivesTo evaluate the benefit and risk of low-dose acetylsalicylic acid (aspirin) in patients from remote Aboriginal communities in the Northern Territory, Australia.DesignRetrospective cohort study using primary care and hospital data routinely used for healthcare. Aspirin users and non-users were compared before and after controlling confounders by matching. Marginal structural models (MSM) were applied to ascertain the benefit and risk.SettingThe benefit and harm of aspirin were investigated in patients aged ≥18 years from 54 remote Aboriginal communities.ParticipantsNone had a previous cardiovascular event or major bleeds. Patients on anticoagulants or other antiplatelets were excluded.InterventionAspirin at a dose of 75-162 mg/day.Outcome measuresEndpoints were all-cause, cardiovascular mortality and incidences of cardiovascular events and major bleeds.Results8167 predominantly Aboriginal adults were included and followed between July 2009 and June 2017 (aspirin users n=1865, non-users n=6302, mean follow-up 4 years with hospitalisations 6.4 per person). Univariate analysis found material differences in demographics, prevalence of chronic diseases and outcome measures between aspirin users and non-users before matching. After matching, aspirin was significantly associated with reduced all-cause mortality (HR=0.45: 95% CI 0.34 to 0.60; p<0.001), but not bleeding (HR=1.13: 95% CI 0.39 to 3.26; p=0.820). After using MSMs to eliminate the effects of confounders, loss of follow-up and time dependency of treatment, aspirin was associated with reduced all-cause mortality (HR=0.60: 95% CI 0.47 to 0.76; p<0.001), independent of age (HR=1.06; p<0.001), presence of diabetes (HR=1.42; p<0.001), hypertension (HR=1.61; p<0.001) and alcohol abuse (HR=1.81; p<0.001). No association between aspirin and major bleeding was found (HR=1.14: 95% CI 0.48 to 2.73; p=0.765). Sensitivity analysis suggested these findings were unlikely to have been the result of unmeasured confounding.ConclusionAspirin was associated with reduced all-cause mortality. Bleeding risk was less compared with survival benefits. Aspirin should be considered for primary prevention in Aboriginal people with high cardiovascular risk.
| S-EPMC6955566 | biostudies-literature
Project description:BackgroundLong-term daily use of aspirin has been associated with reduced cancer mortality. To explore this association, we compared tumour TNM characteristics among aspirin users with those among non-users.MethodsFrom the Swedish Cancer Register, we identified patients diagnosed with colorectal, lung, prostate and breast cancers between 2006 and 2009 and matched them to the Swedish Prescribed Drug Register to obtain information on low-dose aspirin use prior to diagnosis. Contingency table and logistic regression analyses were used to test for association and obtain odds ratios (ORs).ResultsWe identified 17,041 colorectal, 9766 lung, 29,770 prostate and 20,299 breast cancer patients. The proportion of low-dose aspirin users was ~26% among colorectal, lung and prostate cancer patients and ~14% among breast cancer patients. Adjusted for age, gender, education level and place of residence, low-dose aspirin use was associated with lower tumour extent (T) for colorectal and lung cancers (P<0.0001) but not for prostate and breast cancers. The adjusted OR of aspirin use for the T4 vs T1 categories was ~0.7 (95% confidence interval (CI) 0.6-0.8). For all cancers, we found no evidence of association of aspirin use with nodal involvement (N). Except for a borderline result in prostate cancer (OR ~0.9; 95% CI 0.8-1.0), aspirin use was associated with a lower rate of metastatic disease (ORs ~0.6-0.8). Among the histological subgroups of lung cancer, significant differences in tumour extent were observed most clearly within the adenocarcinoma subgroup (OR ~0.6, 95% CI 0.5-0.8), although numbers of other subtypes were more limited; and there was a significant reduction of ~20-30% in the odds of metastasis among the aspirin users across the subgroups.ConclusionUse of low-dose aspirin in the year prior to diagnosis was found to be associated with lower tumour extent and fewer metastatic disease for colorectal and lung cancers. For these cancers, the benefit of aspirin use appears to be during both early and late cancer progression.
| S-EPMC3790151 | biostudies-literature
Project description:Meta-analyses have demonstrated that low-dose aspirin reduces the risk of developing adenocarcinoma metastasis, and when colon cancer is detected during aspirin treatment, there is a remarkable 83% reduction in risk of metastasis. As platelets participate in the metastatic process, the antiplatelet action of low-dose aspirin likely contributes to its antimetastatic effect. Cycloxooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) also contributes to metastasis, and we addressed the hypothesis that low-dose aspirin also inhibits PGE2 biosynthesis. We show that low-dose aspirin inhibits systemic PGE2 biosynthesis by 45% in healthy volunteers (P < 0.0001). Aspirin is found to be more potent in colon adenocarcinoma cells than in the platelet, and in lung adenocarcinoma cells, its inhibition is equivalent to that in the platelet. Inhibition of COX by aspirin in colon cancer cells is in the context of the metastasis of colon cancer primarily to the liver, the organ exposed to the same high concentrations of aspirin as the platelet. We find that the interaction of activated platelets with lung adenocarcinoma cells upregulates COX-2 expression and PGE2 biosynthesis, and inhibition of platelet COX-1 by aspirin inhibits PGE2 production by the platelet-tumor cell aggregates. In conclusion, low-dose aspirin has a significant effect on extraplatelet cyclooxygenase and potently inhibits COX-2 in lung and colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of metastasis from adenocarcinomas, and particularly from colon adenocarcinomas, by low-dose aspirin results from its effect on platelet COX-1 combined with inhibition of PGE2 biosynthesis in metastasizing tumor cells. Cancer Prev Res; 9(11); 855-65. ©2016 AACR.
| S-EPMC5093073 | biostudies-literature
Project description:UnlabelledAntiplatelet agents are pivotal for prevention of coronary artery disease and cerebrovascular disease worldwide. Individual patient data meta-analysis indicates that low-dose aspirin causes a 10% risk reduction in pre-eclampsia for women at high individual risk. However, in the last 15 years it has emerged that a significant proportion of aspirin-treated individuals exhibit suboptimal platelet response, determined biochemically and clinically, termed 'aspirin non-responsiveness', 'aspirin resistance' and 'aspirin treatment failure'. More recently, investigation of aspirin responsiveness has begun in pregnant women. This review explores the history and clinical relevance of 'aspirin resistance' applied to high-risk obstetric populations.Tweetable abstractIs 'aspirin resistance' clinically relevant in high-risk obstetrics?
| S-EPMC5069612 | biostudies-literature