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Background: Prior epidemiological and intervention studies have not been able to separate independent effects of dose, timing, and duration of aspirin use in colorectal cancer (CRC) chemoprevention. We examined aspirin-based CRC chemoprevention according to timing in the Nurses' Health Study and Health Professionals Follow-Up Study.Methods: The exposures include cumulative average dose and total duration of aspirin use in more than 10 years before follow-up started (remote period) and in the immediate 10 years before follow-up started (recent period). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for exposures and CRC risk.Results: Aspirin use of longer than 10 years before follow-up started (HR = 0.88, 95% CI = 0.83 to 0.94) per 5-year increment and the immediate 10 years before follow-up started (HR = 0.90, 95% CI = 0.84 to 0.96) were similarly important in CRC chemoprevention, though a 5-year lag was required for a clear benefit in the recent period. In the remote period, the association was not dose dependent; compared with less than 0.5 standard-dose (325 mg) tablets per week; hazard ratios were 0.78 (95% CI = 0.63 to 0.98), 0.81 (95% CI = 0.72 to 0.91), and 0.74 (95% CI = 0.64 to 0.86) for doses of 0.5 to less than 1.5, 1.5 to less than 5, and 5 and more tablets per week, respectively. However, there was dose dependency in the recent period (with respective HR = 0.91, 95% CI = 0.79 to 1.06; HR = 0.87, 95% CI = 0.77 to 0.98; and HR = 0.76, 95% CI = 0.64 to 0.91).Conclusions: A suggestive benefit necessitates at least 6-10 years and most clearly after approximately 10 years since initiation of aspirin. Remote use and use within the previous 10 years both contribute independently to decrease risk, though a lower dose may be required for a benefit with longer term use. [ABSTRACT FROM AUTHOR]

Introduction The use of aspirin in patients without cardiovascular disease remains controversial. Patients’ understanding of the risks and benefits of aspirin likely contribute to the decision of whether or not to use aspirin regularly. The purpose of this study is to assess patients’ knowledge of aspirin and identify factors contributing to regular use. Methods A survey of U.S. adults aged 45–75 years was performed to ascertain aspirin use and factors that may be associated with use. Multivariate logistic regression was used to identify predictors of current use of aspirin among those with a primary prevention indication. The survey was completed in 2012 with data analysis performed in 2013. Results Among 2,509 respondents, 52% reported current aspirin use. Among 2,039 respondents without a history of cardiovascular disease, current use of aspirin was 47%. Regular use of aspirin for primary prevention was associated with the presence of major cardiovascular disease risk factors (OR=3.0, 95% CI=2.4, 3.7), high self-assessed knowledge of aspirin (OR=9.1, 95% CI=5.2, 15.7), and having discussed aspirin therapy with a provider (OR=25.9, 95% CI=19.7, 34.1). Several markers of healthy lifestyle choices were also associated with regular use. After multivariate analysis, the strongest independent predictor of regular aspirin use was having discussed aspirin therapy with a provider (OR=23.79, 95% CI=17.8, 31.5). Conclusions Approximately half of the nationwide survey of U.S. adults reported regular aspirin use. Among those with a primary prevention indication, having discussed aspirin with a provider was the strongest predictor of regular use. [ABSTRACT FROM AUTHOR]

Lynch syndrome - caused by pathogenic germline MLH1, MSH2, MSH2, PMS2, or EPCAM variants - is among the most common forms of inherited cancer susceptibility and predisposes to high risks of colorectal cancer, endometrial cancer, and other malignancies. We also eagerly await data from the CaPP3 trial of 1882 Lynch syndrome carriers, which will address the primary question about whether lower aspirin doses (100 mg/day and 300 mg/day) are non-inferior to 600 mg/day in reducing Lynch syndrome-associated colorectal cancer incidence. 378, 2011, 2081-2087 5 J Burn, H Sheth, F Elliott, Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial. [Extracted from the article]

Importance: Aspirin may reduce severity of metabolic dysfunction–associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was −6.6% with aspirin vs 3.6% with placebo (difference, −10.2% [95% CI, −27.7% to −2.6%]; P =.009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (−8.8 vs 30.0 percentage points; mean difference, −38.8 percentage points [95% CI, −66.7 to −10.8]; P =.007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P =.006), reduced absolute hepatic fat content by MRI-PDFF (−2.7% vs 0.9%; mean difference, −3.7% [95% CI, −6.1% to −1.2%]; P =.004]), and reduced relative hepatic fat content by MRI-PDFF (−11.7 vs 15.7 percentage points; mean difference, −27.3 percentage points [95% CI, −45.2 to −9.4]; P =.003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729 Key Points: Question: In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), does 81 mg of aspirin daily reduce the quantity of hepatic fat at 6-month follow-up compared with placebo? Findings: In this phase 2 randomized clinical trial of 80 individuals with MASLD, daily aspirin reduced the quantity of hepatic fat at 6-month follow-up compared with placebo (mean difference, −10.2%). Meaning: In a preliminary randomized clinical trial of adults with MASLD, 6 months of daily low-dose aspirin significantly reduced liver fat content compared with placebo, but findings are preliminary and require confirmation in a larger population. This randomized clinical trial compares use of low-dose aspirin vs placebo in reducing hepatic fat among adult patients with metabolic dysfunction–associated steatotic liver disease (MASLD) without cirrhosis. [ABSTRACT FROM AUTHOR]

In this large primary prevention trial in community-dwelling persons aged 70 years or older, daily low-dose aspirin increased the risk for incident anemia by approximately 20%. These findings question preventive use of aspirin in older patients and suggest caution with this practice. Visual Abstract. Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: In this large primary prevention trial of aspirin in community-dwelling persons aged 70 years or older, daily low-dose aspirin increased the risk of incident anemia by approximately 20%. These findings question preventive use of aspirin in older patients and suggest caution with this practice. Background: Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia. Objective: To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations. Design: Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583) Setting: Primary/community care in Australia and the United States. Participants: Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons). Intervention: 100 mg of aspirin daily or placebo. Measurements: Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset. Results: 19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results. Limitations: Hemoglobin was measured annually. No data were available on causes of anemia. Conclusion: Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin. Primary Funding Source: National Institutes of Health and Australian National Health and Medical Research Council. [ABSTRACT FROM AUTHOR]

A response to a commentary that delved on a study which examined the potential for aspirin and COX-2 inhibitors to prevent the recurrence and or death in early-stage colon cancer patients is presented.

Introduction: The relationships among PIK3CA mutations, medication use and tumor progression remains poorly understood. Aspirin use post-diagnosis may modify components of the PI3K pathway, including AKT and mTOR, and has been associated with lower risk of breast cancer recurrence and mortality. We assessed time to metastasis (TTM) and survival with respect to aspirin use and tumor PIK3CA mutations among women with metastatic breast cancer.Methods: Patients with hormone receptor positive, HER2 negative (HR+/HER2-) metastatic breast cancer treated in 2009-2016 who received tumor genotyping were included. Aspirin use between primary and metastatic diagnosis was extracted from electronic medical records. TTM and survival were estimated using Cox proportional hazards regression.Results: Among 267 women with metastatic breast cancer, women with PIK3CA mutated tumors had longer TTM than women with PIK3CA wildtype tumors (7.1 vs. 4.7 years, p = 0.008). There was a significant interaction between PIK3CA mutations and aspirin use on TTM (p = 0.006) and survival (p = 0.026). PIK3CA mutations were associated with longer TTM among aspirin non-users (HR = 0.60 95% CI:0.44-0.82 p = 0.001) but not among aspirin users (HR = 1.57 0.86-2.84 p = 0.139). Similarly, PIK3CA mutations were associated with reduced mortality among aspirin non-users (HR = 0.70 95% CI:0.48-1.02 p = 0.066) but not among aspirin users (HR = 1.75 95% CI:0.88-3.49 p = 0.110).Conclusions: Among women who develop metastatic breast cancer, tumor PIK3CA mutations are associated with slower time to progression and mortality only among aspirin non-users. Larger studies are needed to confirm this finding and examine the relationship among aspirin use, tumor mutation profile, and the overall risk of breast cancer progression. [ABSTRACT FROM AUTHOR]

Background: More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection.Methods: Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events.Results: With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4).Conclusions: In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.). [ABSTRACT FROM AUTHOR]

At the 2019 International Aspirin Foundation Scientific Conference 'Benefits and Risks of Antithrombotic Therapy for Cardiovascular Disease Prevention', held in Rome, Italy, international experts sought to discuss and debate the optimal antithrombotic strategy for the secondary prevention of cardiovascular disease (CVD) and to seek agreement around dosing and target populations for aspirin use in primary disease prevention. Getting the best evidence to support real-life decisions in the clinic can be complex, and individualising management in order to balance both the risks and benefits of different disease prevention strategies appears to be the best approach. It is hoped that future decisionmaking tools and biomarkers will help direct treatments at those most likely to benefit. [ABSTRACT FROM AUTHOR]

Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort. Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01. 16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01. The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging. [ABSTRACT FROM AUTHOR]

Acetylsalicylic acid was first synthesised by Dr FeIix Hoffman on 10th August 1897 and Aspirin was born. It quickly became the best-known pain killer in the world and in the 120 years since this event, aspirin has continued to attract interest, innovation and excitement. Set within the walls of the preserved ruins of Rudolf Virchow's lecture hall at Charité, within Berlin's Museum of Medical History, the International Aspirin Foundation's 28th Scientific Conference served to facilitate international, multi-disease, multidisciplinary discussion about the current understanding of aspirin's mechanisms of action and its utility in modern medicine as well as ideas for future research into its multifaceted applications to enhance global health. In addition to the delegates in Berlin, 300 medical doctors at the 19th Annual Scientific Congress of the Chinese Society of Cardiology were able to join the cardiology sessions from Taiyuan, Shangxi province via a live streaming link to and from China. This led to useful discussion and allowed a truly international perspective to the meeting. [ABSTRACT FROM AUTHOR]

Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Association of Aspirin and NSAID Use With Risk of Colorectal Cancer According to Genetic Variants" is presented.

We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients. [ABSTRACT FROM PUBLISHER]

Simple Summary: Prostate cancer is a common disease in older men, yet current risk prediction models for prostate cancer do not discriminate between men at higher risk of aggressive, clinically significant disease compared to those with benign disease. If risk prediction models can be improved to identify the risk of clinically significant disease with more precision, it could help to reduce over-diagnosis, over-screening, and unnecessary invasive procedures, especially in older men. We examined whether the use of a genomic risk score improves the precision and discriminative ability of prostate cancer risk prediction in men aged 70 years and older. In a population of 5701 healthy older men, we found that the genomic risk score was strongly associated with future prostate cancer risk. However, we observed no association between the genomic risk score and more aggressive, clinically significant prostate cancer—thereby limiting the clinical utility of the genomic risk score. Despite the high prevalence of prostate cancer in older men, the predictive value of a polygenic risk score (PRS) remains uncertain in men aged ≥70 years. We used a 6.6 million-variant PRS to predict the risk of incident prostate cancer in a prospective study of 5701 men of European descent aged ≥70 years (mean age 75 years) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial. The study endpoint was prostate cancer, including metastatic or non-metastatic disease, confirmed by an expert panel. After excluding participants with a history of prostate cancer at enrolment, we used a multivariable Cox proportional hazards model to assess the association between the PRS and incident prostate cancer risk, adjusting for covariates. Additionally, we examined the distribution of Gleason grade groups by PRS group to determine if a higher PRS was associated with higher grade disease. We tested for interaction between the PRS and aspirin treatment. Logistic regression was used to independently assess the association of the PRS with prevalent (pre-trial) prostate cancer, reported in medical histories. During a median follow-up time of 4.6 years, 218 of the 5701 participants (3.8%) were diagnosed with prostate cancer. The PRS predicted incident risk with a hazard ratio (HR) of 1.52 per standard deviation (SD) (95% confidence interval (CI) 1.33–1.74, p < 0.001). Men in the top quintile of the PRS distribution had an almost three times higher risk of prostate cancer than men in the lowest quintile (HR = 2.99 (95% CI 1.90–4.27), p < 0.001). However, a higher PRS was not associated with a higher Gleason grade groups. We found no interaction between aspirin treatment and the PRS for prostate cancer risk. The PRS was also associated with prevalent prostate cancer (odds ratio = 1.80 per SD (95% CI 1.65–1.96), p < 0.001).While a PRS for prostate cancer is strongly associated with incident risk in men aged ≥70 years, the clinical utility of the PRS as a biomarker is currently limited by its inability to select for clinically significant disease. [ABSTRACT FROM AUTHOR]