Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 527-527
Author(s):  
Joseph Sung ◽  
Kelvin Kf Tsoi
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Bleeding ◽  
Large Scale ◽  
Low Dose ◽  
Population Based ◽  
Dose Aspirin ◽  
Increased Risk ◽  
Incidence And Mortality ◽  
Low Dose Aspirin

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]

scholarly journals Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study

2020 ◽  
Vol 9 (4) ◽  
pp. 928
Author(s):  
Luis A. García Rodríguez ◽  
Angel Lanas ◽  
Montse Soriano-Gabarró ◽  
Pareen Vora ◽  
Lucía Cea Soriano
Keyword(s):  
Observational Study ◽  
Gastrointestinal Bleeding ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Low Dose ◽  
Population Based ◽  
Lower Gastrointestinal Bleeding ◽  
Aspirin Therapy ◽  
Dose Aspirin ◽  
Low Dose Aspirin

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75–300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases. In nested case–control analyses, adjusted odds ratios (ORs) were calculated for concomitant PPI use vs. past (discontinued) PPI use among current low-dose aspirin users. For UGIB (n = 987), ORs (95% CIs) were 0.69 (0.54–0.88) for >1 month PPI use and 2.65 (1.62–4.3) for ≤1 month PPI use. Among the latter group, ORs (95% CIs) were 3.05 (1.75–5.33) for PPI initiation after start of aspirin therapy, and 1.66 (0.63–4.36) for PPI initiation on/before start of aspirin therapy. For LGIB (n = 1428), ORs (95% CIs) were 0.98 (0.81–1.17) for >1 month PPI use and 1.12 (0.73–1.71) for ≤1 month PPI use. Among low-dose aspirin users, maintaining PPI use (>1 month) was associated with a significantly reduced UGIB risk. Neither short nor long-term PPI use affected LGIB risk.

Low-Dose Aspirin Use After Diagnosis of Colorectal Cancer Does Not Increase Survival: A Case–Control Analysis of a Population-Based Cohort

2014 ◽  
Vol 146 (3) ◽  
pp. 700-708.e2 ◽  
Author(s):  
Chris R. Cardwell ◽  
Andrew T. Kunzmann ◽  
Marie M. Cantwell ◽  
Carmel Hughes ◽  
John A. Baron ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Low Dose ◽  
Population Based ◽  
Case Control ◽  
Control Analysis ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Case Control Analysis

ASAMET: A randomized, 2x2 biomarker prevention trial of low-dose aspirin and metformin in colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1591-TPS1591 ◽  
Author(s):  
Marilena Petrera ◽  
Laura Paleari ◽  
Matteo Puntoni ◽  
Silvia Caviglia ◽  
Matteo Clavarezza ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Low Dose ◽  
Epidemiological Studies ◽  
Phase Iii ◽  
Beta Catenin ◽  
Mtor Inhibition ◽  
Primary Tumors ◽  
Dose Aspirin ◽  
Incidence And Mortality ◽  
Low Dose Aspirin

TPS1591 Background: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin (ASA) can inhibit colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin (MET) has also been associated with decreased CRC incidence and mortality in meta-analyses of epidemiological studies in diabetics and has been shown to decrease by 40% colorectal adenoma recurrence in a randomized trial. Recent studies have shown that ASA is an inhibitor of mTOR/S6K1 and an activator of AMPK, targeting regulators of intracellular energy homeostasis and metabolism, and that the combination of ASA and MET, another AMPK activator and S6K1 inhibitor, has a striking additive effect on AMPK activation and mTOR inhibition, with increased autophagy and decreased cell growth in CRC cell lines. While both drugs are being tested as single agents, their combination has not been tested in clinical trials. Methods: This is a randomized, placebo-controlled, double-blind, 2x2 biomarker trial of ASA and MET to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery, 160 patients with stage I-III CRC will randomly be assigned in a 4-arm trial to either ASA, 100mg qd, MET 850mg bid, their combination, or placebo for 1 year. The primary endpoint is the change, defined as the difference between pre- and post-treatment expression, of NFκBin the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in paired colonoscopies one year apart. Additional biomarkers will include: 1) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome-wide gene expression arrays; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of mutations and SNPs with treatment response by NGS of primary tumors; 4) the measurement of circulating IL-6, CRP and VEGF, and 5) plasma and colonic MET concentrations and their correlation with biomarker profiles. A favorable biomarker modulation may provide important clues for a subsequent phase III adjuvant trial. Clinical trial information: EudraCT Number: 2015-004824-77.

scholarly journals Maintenance use of non-steroidal anti-inflammatory drugs and risk of gastrointestinal cancer in a nationwide population-based cohort study in Sweden

BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e021869 ◽  
Author(s):  
Nele Brusselaers ◽  
Jesper Lagergren
Keyword(s):  
Gastrointestinal Cancer ◽  
Low Dose ◽  
Population Based ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Cancer Types ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Cox 2 Inhibitors

ObjectivesAspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are potential candidates for chemoprevention of gastrointestinal cancer. We aimed to assess the association between contemporary NSAID use (≥180 days) and gastrointestinal cancer.DesignNationwide Swedish population-based cohort study (2005–2012).SettingSwedenParticipantsAll adults exposed to maintenance NSAIDs use (aspirin, n=783 870; unselective NSAIDs, n=566 209, selective cyclo-oxygenase (COX)-2 inhibitors, n=17 948) compared with the Swedish background population of the same age, sex and calendar period.Outcome measuresThe risk of different gastrointestinal cancer types expressed as standardised incidence ratios (SIR) and 95% CIs, taking into account concurrent proton pump inhibitors (PPIs) and statins usage.ResultsThe SIR for gastrointestinal cancer for aspirin use was 1.02 (95% CI 1.00 to 1.04), with clearly reduced risk for long-term users (SIR=0.31, 95% CI 0.30 to 0.33 for 5.5–7.7 years), but an increased risk for short-term users (SIR=2.77, 95% CI 2.69 to 2.85), and stronger protective effect for low-dose aspirin (SIR=0.86, 95% CI 0.85 to 0.88). Users of non-selective NSAIDs showed an overall decreased risk of gastrointestinal cancer (SIR=0.79, 95% CI 0.77 to 0.82), in particular for cancer of the stomach, colorectum and oesophagus, and the SIRs were further decreased among long-term users. Users of selective COX-2 inhibitors showed a SIR=0.89 (95% CI 0.73 to 1.09) for gastrointestinal cancers. Both aspirin and unselective NSAIDs users who also were using PPIs, had higher risks for all gastrointestinal cancer types; and lower risk if using statins.ConclusionLong-term use of (low-dose) aspirin and non-selective NSAIDs was associated with a decreased risk of all gastrointestinal cancer types.

Low-dose aspirin and risk of intracranial bleeds

Neurology ◽  
2017 ◽  
Vol 89 (22) ◽  
pp. 2280-2287 ◽  
Author(s):  
Lucía Cea Soriano ◽  
David Gaist ◽  
Montse Soriano-Gabarró ◽  
Susan Bromley ◽  
Luis A. García Rodríguez
Keyword(s):  
Low Dose ◽  
Reference Group ◽  
Population Based ◽  
The United Kingdom ◽  
Dose Aspirin ◽  
Increased Risk ◽  
Low Dose Aspirin ◽  
Adjusted Rate ◽  
Rate Ratios ◽  
Incident Cases

Objective:To quantify the risk of intracranial bleeds (ICBs) associated with new use of prophylactic low-dose aspirin using a population-based primary care database in the United Kingdom.Methods:A cohort of new users of low-dose aspirin (75–300 mg; n = 199,079) aged 40–84 years and a 1:1 matched cohort of nonusers of low-dose aspirin at baseline were followed (maximum 14 years, median 5.4 years) to identify incident cases of ICB, with validation by manual review of patient records or linkage to hospitalization data. Using 10,000 frequency-matched controls, adjusted rate ratios (RRs) with 95% confidence intervals (CIs) were calculated for current low-dose aspirin use (0–7 days before the index date [ICB date for cases, random date for controls]); reference group was never used.Results:There were 1,611 cases of ICB (n = 743 for intracerebral hemorrhage [ICH], n = 483 for subdural hematoma [SDH], and n = 385 for subarachnoid hemorrhage [SAH]). RRs (95% CI) were 0.98 (0.84–1.13) for all ICB, 0.98 (0.80–1.20) for ICH, 1.23 (0.95–1.59) for SDH, and 0.77 (0.58–1.01) for SAH. No duration of use or dose–response association was apparent. RRs (95% CI) for ≥1 year of low-dose aspirin use were 0.90 (0.72–1.13) for ICH, 1.20 (0.91–1.57) for SDH, and 0.69 (0.50–0.94) for SAH.Conclusion:Low-dose aspirin is not associated with an increased risk of any type of ICB and is associated with a significantly decreased risk of SAH when used for ≥1 year.

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