Current Aspirin Use Research Articles

Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.

To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use. We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Immigration and use of preventive aspirin by Hispanics and non-Hispanic whites and non-Hispanic blacks in the US

BackgroundIn the US, little is known about aspirin use as a preventive measure for cardiovascular disease by immigration status. MethodsCombined data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 and 2017- March 2020 (pre-pandemic data) were analyzed. Persons were asked about demographics including country of birth and those aged 40 years and older were asked about current use of aspirin to prevent cardiovascular disease (CVD). ResultsAmong 2,321 born in the US, preventive aspirin use was significantly more prevalent (39.6%) than among 910 others (27.5%, p < 0.01). However, after stratifying by race/ethnicity and history of CVD, the difference was significant only in Hispanics with CVD. In logistic regression analyses in Hispanics controlling for age, gender and education, the US born had significantly higher odds of aspirin use in those with or without CVD. DiscussionAmong US Hispanics, use of aspirin for prevention of CVD was more prevalent in those born in the US than in others.

Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women

Several studies evaluated the association between aspirin use and risk of breast cancer (BC), with inconsistent results. We identified women aged ≥ 50 years residing in Norway between 2004 and 2018, and linked data from nationwide registries; including the Cancer Registry of Norway, the Norwegian Prescription Database, and national health surveys. We used Cox regression models to estimate the association between low-dose aspirin use and BC risk, overall and by BC characteristics, women’s age and body mass index (BMI), adjusting for sociodemographic factors and use of other medications. We included 1,083,629 women. During a median follow-up of 11.6 years, 257,442 (24%) women used aspirin, and 29,533 (3%) BCs occurred. For current use of aspirin, compared to never use, we found an indication of a reduced risk of oestrogen receptor-positive (ER +) BC (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.92–1.00), but not ER-negative BC (HR = 1.01, 95%CI: 0.90–1.13). The association with ER + BC was only found in women aged ≥ 65 years (HR = 0.95, 95%CI: 0.90–0.99), and became stronger as the duration of use increased (use of ≥ 4 years HR = 0.91, 95%CI: 0.85–0.98). BMI was available for 450,080 (42%) women. Current use of aspirin was associated with a reduced risk of ER + BC in women with BMI ≥ 25 (HR = 0.91, 95%CI: 0.83–0.99; HR = 0.86, 95%CI: 0.75–0.97 for use of ≥ 4 years), but not in women with BMI < 25.Use of low-dose aspirin was associated with reduced risk of ER + BC, in particular in women aged ≥ 65 years and overweight women.

Correction to: Current regular aspirin use and mammographic breast density: a cross-sectional analysis considering concurrent statin and metformin use

Correction to: Current regular aspirin use and mammographic breast density: a cross-sectional analysis considering concurrent statin and metformin use

Abstract 5893: Analgesic use and renal cell carcinoma incidence and survival: Results from three prospective cohort studies

Abstract Background: Analgesics are the most commonly consumed over-the-counter drugs worldwide. Considerable evidence suggests a beneficial effect of analgesics, and especially aspirin, on cardiovascular disease and colorectal cancer risk. Studies examining whether widely used analgesics - aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen - play a role in renal cell carcinoma (RCC) have yielded mixed results. Methods: We examined associations between pre-diagnostic analgesic use and incidence of total and fatal RCC in the Health Professionals Follow-up Study (HPFS; 1986-2016), Nurses’ Health Study (NHS; 1980-2016 for aspirin; 1990-2016 for non-aspirin NSAIDs and acetaminophen), and Nurses’ Health Study 2 (NHS2; 1989-2015; total RCC only). Information on use of aspirin, non-aspirin NSAIDs, and acetaminophen was collected longitudinally on biennial questionnaires. We used Cox proportional hazards models to estimate cohort-specific, multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) according to current use (updated in each questionnaire period) and, separately, duration of use (since study baseline) of each analgesic. Results across cohorts were combined using random-effects meta-analyses. We also used Cox regression to evaluate post-diagnostic analgesic use with respect to RCC-specific mortality among RCC cases in the pooled HPFS and NHS cohorts. Results: Among 259,545 participants, 796 incident RCC cases were diagnosed. Neither current nor duration of pre-diagnostic use of any of the analgesics was associated with the risk of total RCC in meta-analyses of the three study cohorts. For fatal RCC (n=175 cases), however, meta-analyses of the HPFS and NHS suggested covariate-adjusted positive associations with current (HR: 1.37, 95% CI: 0.96-1.96, p-heterogeneity: 0.80) and duration of (HR&amp;gt;10yrs vs. Never: 2.62, 95% CI: 1.23-5.58, p-trend: 0.006, p-heterogeneity: 0.30) pre-diagnostic non-aspirin NSAID use. In addition, in the HPFS only, current (HR: 2.35, 95% CI: 1.33-4.17) and duration of (HR&amp;gt;10yrs vs. Never: 1.83, 95% CI: 0.42-7.93, p-trend: 0.07) pre-diagnostic acetaminophen use indicated positive associations with fatal RCC. Analyses of RCC-specific mortality among participants diagnosed with RCC demonstrated an inverse association with current post-diagnostic aspirin use (HR: 0.68, 95% CI: 0.48-0.97), but not duration of post-diagnostic aspirin use (HR&amp;gt;10yrs vs. Never: 0.89, 95% CI: 0.53-1.51, p-trend: 0.98). Analgesics were not otherwise associated with RCC survival. Conclusions: Our findings support a potential positive association between non-aspirin NSAID use and incident fatal RCC. It remains possible that analgesics may operate differently in the setting of RCC from the context of other chronic diseases. Citation Format: Rebecca E. Graff, Alejandro Sanchez, Toni K. Choueiri, Meir J. Stampfer, Edward L. Giovannucci, Lorelei A. Mucci, Eunyoung Cho, Mark A. Preston. Analgesic use and renal cell carcinoma incidence and survival: Results from three prospective cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5893.

Current regular aspirin use and mammographic breast density: a cross-sectional analysis considering concurrent statin and metformin use.

The nonsteroidal anti-inflammatory drug aspirin is an agent of interest for breast cancer prevention. However, it is unclear if aspirin affects mammographic breast density(MBD), a marker of elevated breast cancer risk, particularly in the context of concurrent use of medications indicated for common cardiometabolic conditions, which may also be associated with MBD. We used data from the New York Mammographic Density Study for 770 women age 40-60years old with no history of breast cancer. We evaluated the association between current regular aspirin use and MBD, using linear regression for continuous measures of absolute and percent dense areas and absolute non-dense area, adjusted for body mass index (BMI), sociodemographic and reproductive factors, and use of statins and metformin. We assessed effect modification by BMI and reproductive factors. After adjustment for co-medication, current regular aspirin use was only positively associated with non-dense area (β = 18.1, 95% CI: 6.7, 29.5). Effect modification by BMI and parity showed current aspirin use to only be associated with larger non-dense area among women with a BMI ≥ 30 (β = 28.2, 95% CI: 10.8, 45.7), and with lower percent density among parous women (β = -3.3, 95% CI: -6.4, -0.3). Independent of co-medication use, current regular aspirin users had greater non-dense area with stronger estimates for women with higher BMI. We found limited support for an association between current aspirin use and mammographically dense breast tissue among parous women.

Use of Preventive Aspirin Among Older US Adults With and Without Diabetes

The net benefit of aspirin for prevention of cardiovascular disease (CVD), particularly primary prevention, remains debated in people with and without diabetes. Recent studies suggest that the benefits of preventive aspirin may be outweighed by the potential for harm in older adults; therefore, it is important to monitor current aspirin use in order to minimize risk for future harm in the oldest segment of the population. To determine the prevalence of preventive aspirin use in older US adults with and without diabetes for both primary and secondary prevention by age, sex, and CVD risk category. This cross-sectional analysis used nationally representative data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 7103 individuals 60 years or older with and without diabetes completed a questionnaire on preventive aspirin use. Statistical analyses were performed from July 1, 2019, to April 1, 2021. Preventive aspirin use was defined as participants' self-reported use of low-dose aspirin therapy based on their physician's advice or their own decision. A total of 7103 individuals (mean [SD] age, 69.6 [0.1] years; 45.2% men; 75.8% White participants) were evaluated. Overall, 61.7% of older US adults with diabetes vs 42.2% without diabetes used aspirin. Among people with diabetes, in multivariable logistic models adjusting for race, sex, education, CVD risk category, and body mass index, the likelihood of aspirin use in older vs younger age categories (reference: 60-69 years) did not differ. Among people without diabetes, aspirin use was significantly greater in older age categories vs the reference (model 3, 70-79 years, odds ratio [OR], 1.50; 95% CI, 1.23-1.83; model 3, ≥80 years, OR, 1.59; 95% CI, 1.24-2.04). An estimated 9.9 million US adults 70 years or older with or without diabetes reported taking aspirin for primary prevention. The likelihood of aspirin use for primary prevention in those at high vs low risk for CVD did not differ among older adults with diabetes (model 3, OR, 1.69; 95% CI, 0.65-4.39) but was significantly higher in those without diabetes (model 3, OR, 2.46; 95% CI, 1.63-3.71). Women vs men with diabetes were less likely to be using aspirin for primary prevention (model 3, OR, 0.63; 95% CI, 0.48-0.83). This cross-sectional study found that preventive aspirin use was higher among older adults with diabetes than in those without diabetes. Results suggest that 9.9 million older US adults who previously took aspirin for primary prevention would not be recommended for its continued use, particularly among those with diabetes.

Abstract 4348: Cardiorespiratory fitness levels in men who develop prostate cancer and its association with all-cause mortality

Abstract Background: Cardiorespiratory fitness (CRF) is associated with a reduction in both cancer- and cardiovascular-specific mortality. In men however, little is known about the impact of pre-diagnostic CRF on mortality after prostate cancer. We hypothesized that among men with prostate cancer, low levels of CRF, measured prior to diagnosis, are associated with a higher risk of all-cause mortality. Methods: From the Henry Ford FIT Project, a cohort of 37,730 men who underwent clinically-indicated exercise stress test from 1991 through 2009, we identified 1,440 men who developed prostate cancer after stress test. CRF was measured in peak metabolic equivalents of task (METs) and categorized as less than 6, 6 to 9, 10 to 11, and at least 12 (reference). Multivariable Cox proportional hazard models were developed to evaluate the association between CRF, measured prior to prostate cancer diagnosis, and all-cause mortality. Models were adjusted for age at prostate cancer diagnosis (baseline), race, BMI, current aspirin and statin use, smoking history, hypertension, diabetes, prior cardiovascular disease (myocardial infarction and heart failure), time from stress test to prostate cancer diagnosis, and cancer stage (local, regional, distant) at diagnosis. Results: Mean age at time of stress test was 61 +/- 9 yr (57% white, 39% black), with 7 (+/-4) yrs of follow up after prostate cancer diagnosis. 81% of men were diagnosed with localized prostate cancer; 15% with regional disease, and 2% with distant metastatic disease. Mean time from stress test to diagnosis was 6 +/- 5 yrs. Mean METs achieved was 9 (+/- 3). Patients with low fitness (METs less than 6) before diagnosis had 2.6 times the risk of all-cause mortality (95% CI 1.6-4.2) compared to those with high fitness (METS at least 12). Those with CRF of 6-9 METs had 1.9 times the risk (95% CI 1.2-3.0). The risk of mortality was not different between the two highest fitness groups (P= 0.71; P for trend across all fitness groups less than 0.01). Results were similar when stratified by race. Conclusion: Low CRF prior to the diagnosis of prostate cancer in men is associated with a higher risk of all-cause mortality. This study highlights the prognostic importance of fitness even before a cancer diagnosis. Citation Format: Cara Reiter-Brennan, Omar Dzaye, Mouaz H. Al-Mallah, Zeina Dardari, Clinton A. Brawner, Lois E. Lamerato, Steven J. Keteyian, Jonathan K. Ehrman, Kala Visvanathan, Michael J. Blaha, Catherine Handy Marshall. Cardiorespiratory fitness levels in men who develop prostate cancer and its association with all-cause mortality [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4348.

Patient and institutional factors associated with postoperative opioid prescribing after common vascular procedures

ObjectiveOverprescription of postoperative opioid medication is a major contributor to the opioid abuse epidemic in the United States. Research into prescribing practices has suggested that patients be limited to 7 days or <200 morphine milligram equivalents (MME) after surgical procedures. Our aim was to identify patient or institutional factors associated with increased opioid prescriptions. MethodsOpioid naive patients from an integrated health system undergoing one of nine surgical and endovascular procedures tracked within the Vascular Quality Initiative from 2015 to 2017 were identified and matched to their discharge and refill opioid prescriptions. Discharge opioid prescriptions were converted to MME. The primary outcome was discharge MME >200, and secondary outcomes were procedure-specific top-quartile opioid prescription and medication refills. Multivariable logistic regression was used to assess patient and perioperative factors associated with each outcome. ResultsAmong 1546 opioid naive patients, 739 (48%) received a discharge opioid prescription; median MME was 0 (interquartile range, 0-150), and 349 (23%) had >200 MME. Among those with a discharge prescription, median MME was 180 (interquartile range, 150-300). MME varied by procedure (P < .001), with highest MME after suprainguinal bypass (median, 225) and infrainguinal bypass (200) and lowest MME after carotid artery stenting, carotid endarterectomy, and percutaneous peripheral vascular intervention (all medians of 0). On multivariable analysis, factors associated with MME >200 included younger patient age (<65 vs ≥ 80 years; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9-4.6; P < .001), treating institution B vs A (OR, 3.50; 95% CI, 2.42-5.07; P < .001) and C vs A (OR, 3.90; 95% CI, 2.66-5.74; P < .001), procedure-specific top-quartile length of stay (OR, 1.45; 95% CI, 1.01-2.08; P = .047), and prior tobacco use (OR, 1.60; 95% CI, 1.07-2.37; P = .02). The same variables along with current tobacco use and lack of preoperative aspirin were associated with procedure-specific top-quartile MME at discharge. Chronic beta-blocker use was protective of top-quartile MME. Based on the observed variability, an institutional standard for opioid prescribing has been developed for standardization. ConclusionsOpioid prescriptions at discharge vary with the invasiveness of vascular surgical procedures. Less than 25% of patients receive >200 MME. Variation by center represents a lack of standardization in prescribing practices and an opportunity for further improvement based on developed guidelines. Patient factors and procedure type can alert clinicians to patients at risk of higher than recommended MME.

Abstract MP64: The Role of Aspirin in the Relationship Between Hypertensive Disorders of Pregnancy and Incident Maternal Cardiovascular Disease

Introduction: Hypertensive disorders of pregnancy (HDP; including gestational hypertension and preeclampsia) are associated with an increased risk of maternal cardiovascular disease (CVD). Low-dose aspirin reduces the risk of preterm preeclampsia, through proposed short-term effects on platelet and endothelial function. While low-dose aspirin is recommended for the prevention of preeclampsia in women at high risk, no recommendations exist for aspirin use following a pregnancy complicated by HDP. Hypothesis: We hypothesized that regular aspirin use after pregnancy would modify the association between HDP and CVD, lowering the magnitude of the association among aspirin users relative to non-users. Methods: Parous women free of CVD before first birth in the Nurses’ Health Study II comprised the analytic sample (n=60,392). Lifetime pregnancy history was reported in 2009. Women were followed for confirmed incident CVD (coronary heart disease [non-fatal or fatal MI, fatal CHD] or stroke [non-fatal or fatal]) from 1989 through 2013. Current regular aspirin use was self-reported at baseline in 1989 and updated every 2 years via biennial questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the relationship between HDP in first pregnancy (using 3 mutually exclusive categories: normotension [ref], gestational hypertension, preeclampsia) and CVD, adjusted for age, race/ethnicity, parental education, family history of CVD &lt;60y, and pre-pregnancy risk factors (smoking, physical activity, diet, alcohol intake, oral contraceptive use, BMI). Effect modification by aspirin was tested through a likelihood ratio test, comparing nested models with and without interaction terms between HDP history and time-varying aspirin use. Results: Nine percent of women (n=5,629) had HDP in first pregnancy. CVD events occurred in 657 women with normotension, 30 women with gestational hypertension, and 75 women with preeclampsia. Compared to women with normotension in first pregnancy, gestational hypertension was associated with stroke (HR=1.65; CI: 1.01-2.71) but not CHD (HR=1.21; CI: 0.70-2.12), while preeclampsia was associated with CHD (HR=2.27; CI: 1.69-3.04) but not stroke (HR=1.03; CI: 0.68-1.57). Current aspirin use was not a significant effect modifier of the relationship between HDP and CVD (p-value=0.53). Hazard ratios for the relationship between gestational hypertension and CVD were 1.58 (CI: 1.01-2.49) among aspirin non-users and 1.15 (CI: 0.61-2.18) among aspirin users. Hazard ratios for the relationship between preeclampsia and CVD were 1.52 (CI: 1.10-2.10) among aspirin non-users and 1.67 (CI: 1.16-2.40) among aspirin users. Conclusion: Aspirin use after pregnancy does not appear to modify the increased risk of CVD observed among women with a history of HDP compared to women with normotension in pregnancy.

Abstract 5247: Aspirin use and estrogen receptor-negative breast cancer risk in African American women

Abstract Introduction: Use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been hypothesized to be associated with reduced risk of breast cancer; however, results of epidemiological studies have been mixed. Further, few previous studies investigated these associations among African American women and no studies that included African Americans evaluated whether associations differ by estrogen receptor (ER) status. Methods: To assess the relation of aspirin use to risk of ER+ and ER- breast cancer in African American women, we conducted a prospective analysis within the Black Women's Health Study, an ongoing nationwide cohort of 59,000 black women that began in 1995. On baseline and biennial follow-up questionnaires, women reported regular aspirin use (defined as use at least three days per week) and years of use. Acetaminophen use was queried similarly. Among women with available information on aspirin use, 1701 invasive breast cancers occurred during follow-up through 2015, including 962 ER+ and 492 ER- tumors. All cancers were confirmed through pathology reports or state cancer registry data. We used age-stratified Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of aspirin use with risk of ER+ and ER- breast cancer. All models adjusted for age at menarche, oral contraceptive use, parity, age at first birth, estrogen plus progestin use, body mass index, alcohol consumption, and use of other NSAIDs. Results: Compared to never use, current regular use of aspirin was associated with lower risk of breast cancer overall (HR 0.87; 95% CI 0.76, 1.00). The association was driven by a statistically significant inverse association for ER- breast cancer (HR 0.76; 95% CI 0.58, 0.99); for ER+ breast cancer, the corresponding HR was 0.92 (95% CI 0.77, 1.09). In contrast, we found no associations with acetaminophen use. Conclusions: Our observation of reduced risk of ER- breast cancer in relation to current regular use of aspirin is consistent with anti-inflammatory effects of aspirin, rather than hormone-dependent pathways. Aspirin may represent a potential opportunity for chemoprevention of ER- breast cancer; however, these findings require corroboration in additional studies. Citation Format: Kimberly A. Bertrand, Traci N. Bethea, Hanna Gerlovin, Patricia Coogan, Lucile L. Adams-Campbell, Lynn Rosenberg, Julie R. Palmer. Aspirin use and estrogen receptor-negative breast cancer risk in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5247.

Pre-admission use of platelet inhibitors and short-term stroke mortality: a population-based cohort study.

The impact of pre-admission antiplatelet treatment on prognosis after stroke is poorly understood. We, therefore, investigated whether pre-admission use of aspirin and clopidogrel was associated with mortality in patients hospitalized with ischaemic stroke, intracerebral haemorrhage (ICH), or subarachnoid haemorrhage (SAH). We used nationwide population-based registries to identify all first-time hospitalizations for stroke and subsequent mortality in patients treated with aspirin and clopidogrel in Denmark during 2004-2012. Based on redeemed prescriptions, we computed absolute 30-day mortality rates and mortality rate ratios (MRRs) for current platelet inhibitor users and non-users. We used Cox regression to control for potentially confounding factors. Among platelet inhibitor non-users, 30-day stroke mortality was 12.0% (8.8% for ischaemic stroke, 29.6% for ICH, and 21.2% for SAH). Compared with non-users, the adjusted 30-day MRR (aMRR) was increased among ICH patients using aspirin [1.19, 95% confidence interval (CI) 1.09-1.31]. Although wider CIs, similar increased point estimates were observed in users of both aspirin and clopidogrel (aMRR = 1.26, 95% CI 0.84-1.91). In contrast, current use of both aspirin and clopidogrel was associated with reduced mortality from ischaemic stroke (aMRR = 0.67, 95% CI 0.48-0.94), while use of aspirin alone was not. Among patients hospitalized for first-time ICH, pre-admission platelet inhibitor use was associated with increased 30-day mortality compared with non-use. In patients hospitalized for ischaemic stroke, 30-day mortality was reduced in users of both aspirin and clopidogrel, but not in users of aspirin alone.

Prevalence and predictors of inappropriate anticoagulation in patients with a CHA2DS2-VASc score of 0 and atrial fibrillation

BackgroundPrevious studies have shown underutilization of anticoagulation therapy in patients with atrial fibrillation and a CHA2DS2-VASc score ≥2; however there exists little data regarding the inappropriate use of anticoagulation in patients with a CHA2DS2-VASc score of 0. We aimed to determine the true prevalence and predictors of inappropriate anticoagulation therapy in patients with atrial fibrillation and a CHA2DS2-VASc score of 0. MethodsA retrospective chart review was performed on all patients with atrial fibrillation and a CHA2DS2-VASc score of 0 in our institution from January 2009 to January 2016. Demographic and clinical data were collected from the electronic medical record. We utilized multivariable logistic regression analysis to determine independent clinical predictors of inappropriate anticoagulation administration. Results512 patients were identified with a CHA2DS2-VASc score of 0 and a diagnosis of atrial fibrillation. Of the 137 patients prescribed anticoagulation, 64 patients were identified as inappropriately treated with anticoagulation therapy after assessing for other indications of warfarin or novel anticoagulant therapy. Independent variables associated with inappropriate anticoagulation administration were age (OR 1.07; 95% CI 1.03–1.10), body mass index (OR 1.06; 95% CI 1.01–1.10), absence of current aspirin use (OR 13.50; 95% CI 6.00–30.54) and persistent atrial fibrillation (OR 2.34; 95% CI 1.11–4.94). ConclusionsOur study shows that 12% of patients with a CHA2DS2-VASc score of 0 were inappropriately prescribed anticoagulant therapy. Independent predictors of unnecessary anticoagulation were age, body mass index, absence of current aspirin use and persistent atrial fibrillation.

Aspirin use is associated with lower mammographic density in a large screening cohort.

Observational and biologic studies suggest that aspirin is a promising prevention therapy for breast cancer. However, clinical trials to date have not corroborated this evidence, potentially due to study design. We evaluated the effect of aspirin on mammographic density (MD), an established modifiable risk factor for breast cancer. Electronic medical records from the University of Pennsylvania were evaluated for women who underwent screening mammography, saw their primary care provider, and had a confirmed list of medications during 2012-2013. Logistic regression was performed to test for associations between clinically recorded MD and aspirin use, after adjusting for age, body mass index (BMI), and ethnicity. We identified 26,000 eligible women. Mean age was 57.3, mean BMI was 28.9kg/m2, 41% were African American, and 19.7% reported current aspirin use. Aspirin users were significantly older and had higher BMI. There was an independent, inverse association between aspirin use and MD (P trend<0.001). Women with extremely dense breasts were less likely to be aspirin users than women with scattered fibroglandular density (OR 0.73; 95% CI 0.57-0.93). This association was stronger for younger women (P=0.0002) and for African Americans (P=0.011). The likelihood of having dense breasts decreased with aspirin dose (P trend=0.007), suggesting a dose response. We demonstrate an independent association between aspirin use and lower MD in a large, diverse screening cohort. This association was stronger for younger and African American women: two groups at greater risk for ER- breast cancer. These results contribute to the importance of investigating aspirin for breast cancer prevention.

Abstract PD1-05: Aspirin use is associated with lower mammographic density in a large screening cohort

Abstract Background: Current breast cancer prevention agents have substantial side effects and do not prevent estrogen receptor negative (ER-) breast cancer. Aspirin is a promising breast cancer prevention therapy; it is cheap, safe, well tolerated, with strong biologic and epidemiologic evidence for a prevention effect on both ER- and ER+ breast cancers. However, clinical trials to date have failed to corroborate a prevention effect; these results are potentially related to study design (dose, duration of therapy and followup, population treated). We sought to evaluate the effect of aspirin on mammographic density, as breast density is a well-accepted, modifiable risk factor for both estrogen receptor positive (ER+) and ER- breast cancer. Methods: Electronic medical records from the University of Pennsylvania were retrospectively evaluated for women from a core set of 36 primary care/ObGyn practices. Individuals were selected if they had both undergone routine screening mammography during 2012-2013 and had an ambulatory visit within the year prior with a confirmed list of medication use. We selected the medication record closest to the screening exam. Logistic regression was performed to test for associations between clinically-recorded BIRADS breast density and aspirin use, after adjusting for the additional risk factors of age, body mass index (BMI) and ethnicity. Results: We identified 26000 women who fit the above criteria, of whom 19.7% reported current aspirin use and 41% were African American. Mean age was 57.3 (standard deviation [sd], 10.9) and mean BMI was 28.9 (sd, 7.3) kg/m2 for the entire cohort. Aspirin users were significantly older and had higher BMI (see Table). There was an independent, inverse association between aspirin use and mammographic density (Ptrend&amp;lt;0.001). Compared to women with extremely dense breasts, women with fatty (OR=1.73, CI: 1.33-2.25) or scattered fibroglandular (OR=1.50; CI: 1.17-1.92) breasts were more likely to be aspirin users. A dose-response pattern was observed, as there was a lower likelihood of having extremely or heterogeneously dense breasts with increasing aspirin dose (OR=0.62, CI: 0.50-0.76 for &amp;gt;300 mg; OR=0.84, CI=0.77-0.91 for &amp;lt;=300 mg; compared to non-users as reference group). The association between aspirin use and density was more pronounced for women &amp;lt;60 and for African American women (p=0.01). Conclusion: We demonstrate an independent association between aspirin use and lower mammographic density in a large, diverse screening cohort. Our results suggest that this association is stronger for younger and African American women: two groups at greater risk for ER- breast cancer. Future evaluation of this cohort will examine duration of aspirin use, and evaluate an automated measure of breast density. These results and others highlight the potential value and need for a randomized, controlled trial of aspirin as a preventive agent for breast cancer. CharacteristicAspirin Non-UsersAspirin UsersPAge, mean (SD)55.3 (10.2)65.3 (9.8)&amp;lt;0.0001BMI, mean (SD)28.5 (7.2)30.4 (7.6)&amp;lt;0.0001Breast density, no. (%) OR (95% CI)BIRADS 12006 (9.6)861 (16.9)1.73 (1.33 - 2.25)BIRADS 29346 (44.7)2859 (55.9)1.50 (1.17 - 1.92)BIRADS 38480 (40.6)1312 (25.7)1.22 (0.95 - 1.56)BIRADS 41057 (5.1)79 (1.6)1.00 (Reference) Citation Format: Wood ME, Sprague BL, Oustimov A, Synnstvedt MB, Cuke M, Emily CF, Kontos D. Aspirin use is associated with lower mammographic density in a large screening cohort. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-05.

NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.

Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥ 40 Years: Data from the National Health and Nutrition Examination Survey, 2011-2012.

We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥ 40 years from the National Health and Nutrition Examination Survey, 2011-2012. In 2011-2012, one-third of U.S. adults aged ≥ 40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40-49 years to 54% of those ≥ 80 years of age, p<0.001). Non-Hispanic white (35%) and black (30%) adults were more likely to take preventive aspirin than non-Hispanic Asian (20%, p<0.001) and Hispanic (22%, p=0.013) adults. Adults with, compared with those without health insurance, and adults with ≥ 2 doctor visits in the past year, diagnosed diabetes, hypertension, or high cholesterol were twice as likely to take preventive aspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use.

Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status.

The TMPRSS2:ERG (T2E) gene fusion is the most common rearrangement in prostate cancer (PCa). It is unknown if these molecular subtypes have a different etiology. We evaluated aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in association with T2E fusion status. Subjects were from a population-based case-control study of PCa. T2E fusion status for prostatectomy cases (n=346) was determined by fluorescence in situ hybridization. Medication use was determined from questionnaires. Logistic regression, controlling for age, race, PCa family history and PSA screening, was used to evaluate the association of T2E fusion status according to medication use. T2E fusion was present in 171 (49%) cases, with younger cases more likely to be fusion positive (P<0.01). Current aspirin use was associated with a 37% risk reduction of T2E-positive tumors (adjusted odds ratio (OR) 0.63, 95% confidence interval 0.43-0.93). Aspirin use was not associated with T2E negative PCa (adjusted OR 0.99, 0.69-1.42). There were no associations between PCa fusion status and use of nonaspirin NSAIDs or acetaminophen. Aspirin was associated with a significant reduction in the relative risk of T2E fusion positive, but not T2E negative, PCa. As inflammation and androgen pathways are implicated in prostate carcinogenesis, additional studies of anti-inflammatory medications in relation to these PCa subtypes are warranted.

Relationship between time spent at extreme International Normalized Ratios and time in therapeutic range with bleeding and thrombosis in warfarin-treated patients.

The relationship between the time spent at extreme International Normalized Ratios (INRs) and the time in the therapeutic range (TTR) with bleeding and thrombosis in warfarin-treated patients was examined. Consecutive patients treated with warfarin for atrial fibrillation or for venous thrombosis who were managed by the anticoagulation management service or adult internal medicine clinic of a large, tertiary care, integrated health system between June 1, 2011, and October 9, 2012, were eligible for study inclusion. Data collected for the outcomes analysis included INRs and dates; current use of aspirin, clopidogrel, prasugrel, ticagrelor, ticlopidine, or nonsteroidal antiinflammatory drugs; and any clinically significant bleeding or thrombosis events identified. In the 837 patients who met the inclusion criteria, 636.5 patient-years of therapy were provided, of which 14.4 patient-years (2.26% of time) were spent at INRs of <1.5; 2.9 patient-years of therapy (0.45% of time) were spent at INRs of >4.5. The patient population had a mean individual TTR of 65%. The percentage of time at an INR of >4.5 was positively associated with an increased risk of major bleeding (p = 0.0085). The percentage of time spent with an INR of <1.5 was not associated with a significant increase in the risk of thrombosis. The percentage of time spent with an INR of >4.5 was associated with an increased risk of major bleeding in patients receiving warfarin for atrial fibrillation or for venous thrombosis at two outpatient clinics. The relationships between thrombosis risk and the TTR or the time spent at an INR of <1.5 were not significant, but the thromboembolic event rate was unusually low, as was the time spent at an INR of <1.5.

Aspirin use among adults in the U.S.: results of a national survey.

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. 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. 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). 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.