OBJECTIVE: There is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial.
DESIGN: Data were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010-2017 ('ASPirin in Reducing Events in the Elderly (ASPREE)', n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm.
RESULTS: Over a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p<0.01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors.
CONCLUSION: Aspirin increases overall GI bleeding risk by 60%; however, the 5-year absolute risk of serious bleeding is modest in younger, well individuals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin.
TRIAL REGISTRATION NUMBER: ASPREE. NCT01038583.
<b>BACKGROUND: </b>ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.<b>METHODS: </b>19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records.<b>RESULTS: </b>981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64).<b>CONCLUSIONS: </b>In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and, thus, suggest caution with its use in this age group.
INTRODUCTION: Aspirin is widely used to prevent cardiovascular diseases (CVDs). However, the balance of its benefits and risks in the primary prevention of CVDs and cancer is unclear, especially in elderly Asians. The present study aimed to evaluate the efficacy of aspirin in the primary prevention of major adverse cardiac and cerebrovascular events (MACCE), bleeding risk, and cancer in elderly Koreans with cardiovascular (CV) risk factors.
METHODS: This retrospective cohort study used data from the Korean National Health Insurance Service-Senior cohort database (2002-2015). Patients aged 60-90 years with hypertension, type 2 diabetes mellitus (T2DM), or dyslipidemia were identified. Aspirin users were compared with non-users using propensity score matching at a 1:3 ratio. The primary outcome was MACCE, a composite of CV mortality, myocardial infarction, and ischemic stroke. The secondary outcomes were the components of MACCE, all-cause mortality, angina pectoris, heart failure, the incidence and mortality of cancer, and the risks of hemorrhagic stroke and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazard model.
RESULTS: A total of 3366 aspirin users and 10,089 non-users were finally included in the study. During a mean follow-up of 7.8 years, the incidence of MACCE was 15.2% in aspirin users and 22.4% in non-users. The risk of MACCE was significantly lower in aspirin users than in non-users (HR 0.76; 95% CI 0.69-0.85), and this risk was significantly reduced in patients using aspirin over 5 years (HR 0.52; 95% CI 0.46-0.60). Aspirin use was associated with a 21% reduction in the risk of primary cancer (HR 0.79; 95% CI 0.70-0.88) and cancer-related mortality (HR 0.72; 95% CI 0.61-0.84). No significant differences in bleeding risks were observed between the two groups.
CONCLUSION: Aspirin reduced the risks of MACCE and cancer without increasing the bleeding risk in elderly Koreans with hypertension, T2DM, or dyslipidemia. Moreover, the benefits of the long-term use of aspirin in reducing the risks of MACCE were demonstrated. However, the decision of using aspirin for primary prevention must be carefully made on an individual basis, while estimating the benefit-risk balance of aspirin.
INTRODUCTION: This post hoc subanalysis of the randomized Japanese Primary Prevention Project investigated whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged ≥ 70 years with atherosclerotic risk factors. METHODS: Patients aged < 70 years (young-old) or ≥ 70 years (old) with hypertension, dyslipidemia, or diabetes participated between 2005 and 2007. Patients were randomized 1:1 to receive 100 mg enteric-coated aspirin once daily or no aspirin plus standard of care. The primary outcome was a composite of death from cardiovascular causes plus nonfatal stroke and nonfatal myocardial infarction. The secondary outcome was a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention. Old (n = 7971) and young-old (n = 6493) patients were followed up for a median 5.02 years. RESULTS: Aspirin did not reduce the risk of primary (hazard ratio [HR] 0.92 [95% confidence interval {CI} 0.74–1.16]; P = 0.50) or secondary (0.85 [0.70–1.04]; P = 0.11) outcomes in patients aged ≥ 70 years. In old men with high-density lipoprotein < 40 mg/dL, treatment with low-dose aspirin was associated with a reduction in the incidence of the primary endpoint compared with the group not receiving aspirin (10/260 vs 22/250; HR 0.44 [95% CI 0.20–0.93]; P = 0.03). This subgroup was also found to contain significant larger proportions of patients with elevated body mass index, patients with diabetes mellitus, and smokers (P < 0.001). Old patients also showed differences in bleeding outcomes. Serious extracranial hemorrhage requiring transfusion or hospitalization occurred significantly more frequently in the aspirin-treated group than in the non–aspirin-treated group (35 [0.88%] vs 18 [0.45%]; HR 1.96 [1.11–3.46]; P = 0.020). Gastrointestinal hemorrhage occurred significantly more frequently in the aspirin-treated group than the non–aspirin-treated group (63 [1.58%] vs 18 [0.45%]; relative risk [RR] 3.5 [2.08–5.90]; P < 0.0001). Cerebral hemorrhage (intracranial hemorrhage) tended to occur more frequently in the aspirin-treated group than the non–aspirin-treated group (22 [0.55%] vs 11 [0.28%]; RR 2.01 [0.97–4.14]; P = 0.058). Cerebral hemorrhage occurred significantly more frequently in old patients than in young-old patients (33 [0.41%] vs 10 [0.15%]; HR 2.7 [1.34–5.53]; P = 0.0055). Gastrointestinal hemorrhage occurred in a slightly higher proportion of old patients compared with young-old patients (81 [1.02%] vs 53 [0.82%]; RR 1.2 [0.88–1.76]; P = 0.21). Discussion/CONCLUSIONS: Aspirin did not reduce the risk of the primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy. Clinical Trial Registration: The study is registered at ClinicalTrials.gov [NCT00225849].
BACKGROUND/PURPOSE: We aimed to identify the risk factors of first-time occurrence of non-variceal upper gastrointestinal bleeding (UGIB) among aspirin users after adjusting for confounding factors like age, gender, underlying co-morbidities, and medications.
METHODS: Using the National Health Insurance Research Database of Taiwan and matching age, gender, underlying co-morbidities and enrollment time by propensity score, 11105 aspirin users and 11105 controls were identified for comparison from a cohort dataset of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify independent risk factors for first-time occurrence of non-variceal UGIB in the study cohort and in the aspirin users after adjusting for age, gender, underlying co-morbidities, and medications (e.g., non-steroidal anti-inflammatory drugs [NSAIDs], cyclooxygenase-2 [COX-2] inhibitors, steroids, thienopyridines, selective serotonin reuptake inhibitors, warfarin, and dipyridamole).
RESULTS: By Cox proportional hazard regression analysis, aspirin use increased the risk of first-time occurrence of UGIB (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.28-1.72). Age, male gender, Helicobacter pylori (H. pylori)infection, diabetes, chronic kidney disease (CKD), cirrhosis, history of uncomplicated peptic ulcer disease (PUD), and use of NSAIDs, COX-2 inhibitors, steroids, and thienopyridines were independent risk factors for UGIB among aspirin users.
CONCLUSION: In addition to age, male gender, H. pylori infection, and concomitant use of NSAIDs, COX-2 inhibitors, steroids, and thienopyridines, underlying co-morbidities including diabetes, CKD, cirrhosis, history of PUD are also important risk factors for first-time occurrence of non-variceal UGIB in aspirin users.
<b>BACKGROUND: </b>Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.<b>METHODS: </b>From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.<b>RESULTS: </b>A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).<b>CONCLUSIONS: </b>Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
This study extends health disparities research by examining racial differences in the relationships between multigenerational attainments and mortality risk among "Silent Generation" women. An emerging literature suggests that the socioeconomic attainments of adjacent generations, one's parents and adult children, provide an array of life-extending resources in old age. Prior research, however, has demonstrated neither how multigenerational resources are implicated in women's longevity nor how racial disparities faced by Silent Generation women may differentially structure the relationships between socioeconomic attainments and mortality. With data from the National Longitudinal Survey of Mature Women, the analysis provided evidence of a three-generation model in which parent occupation, family wealth, and adult child education were independently associated with women's mortality. Although we found evidence of racial differences in the associations between parental, personal, and spousal education and mortality risk, the education of adult children was a robust predictor of survival for black and white women.
BACKGROUND: The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event.
METHODS: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059.
FINDINGS: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group).
INTERPRETATION: The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies.
FUNDING: Bayer.
OBJECTIVE: This study analyzed the efficacy of low-dose aspirin in cancer chemoprevention in patients with diabetes.
RESEARCH DESIGN AND METHODS: This study was a posttrial follow-up of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial. Participants in the JPAD trial (2,536 Japanese patients with type 2 diabetes and without preexisting cardiovascular disease) were randomly allocated to receive aspirin (81 or 100 mg daily) or no aspirin. After that trial ended in 2008, we followed up with the participants until 2015, with no attempt to change the previously assigned therapy. The primary end point was total cancer incidence. We investigated the effect of low-dose aspirin on cancer incidence.
RESULTS: During the median follow-up period of 10.7 years, a total of 318 cancers occurred. The cancer incidence was not significantly different between the aspirin and no-aspirin groups (log-rank, P = 0.4; hazard ratio [HR], 0.92; 95% CI, 0.73-1.14; P = 0.4). In subgroup analyses, aspirin did not affect cancer incidence in men, women, or participants aged ≥65 years. However, it decreased cancer incidence in participants aged <65 years (log-rank, P = 0.05; HR, 0.67; 95% CI, 0.44-0.99; P = 0.048). After adjusting for sex, hemoglobin A1c, smoking status, and administration of metformin and statins, aspirin significantly reduced cancer incidence in participants aged <65 years (adjusted HR, 0.66; 95% CI, 0.43-0.99; P = 0.04).
CONCLUSIONS: Low-dose aspirin did not reduce cancer incidence in Japanese patients with type 2 diabetes.
Essentials The effects of aspirin on cancer incidence and mortality in the elderly Japanese are not clear. We analyzed cancer incidence and mortality in the Japanese Primary Prevention Project (JPPP). Low-dose aspirin for 5 years did not reduce cancer incidence or cancer mortality in the JPPP. Cancers might be diagnosed earlier in the aspirin group. Background: Long-term follow-up of studies to investigate preventive effects of aspirin on arterial thrombosis indicate that aspirin reduces the incidence and mortality of some cancers in Western populations. Objectives: To explore the effects of aspirin on cancer incidence and mortality in the elderly Japanese. Patients/Methods: Patients aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus (n = 14 601, 7297 in the aspirin group and 7304 in the no-aspirin group) participated the Japanese Primary Prevention Project (JPPP), a multicenter, open-label, randomized, parallel-group trial. A subanalysis of JPPP was performed to analyze the incidence of newly diagnosed cancer and death related to cancer. Results: The cumulative incidence of newly diagnosed cancer was 5.60% (4.65-6.64%) in the aspirin group and 4.14% (3.67-4.66%) in the no-aspirin group. The hazard ratio for newly diagnosed cancer was 1.24 (1.06-1.46), and the cancer incidence was significantly higher in the aspirin group. The cumulative cancer mortality was 1.96% (1.65-2.31%) in the aspirin group and 1.87% (1.56-2.22%) in the no-aspirin group, with no statistically significant difference. The Fine and Gray model suggested that the difference in the incidence of newly diagnosed cancer between the two groups decreased year by year. Conclusions: Low-dose aspirin use did not reduce the cancer incidence or cancer mortality during a 5-year-average study period in the elderly Japanese. The cancer incidence in the aspirin group might decrease, however, to less than that in the no-aspirin group after the study period. Aspirin use might have led to earlier cancer diagnosis in our study.
There is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large randomised, controlled trial.
DESIGN:
Data were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010-2017 ('ASPirin in Reducing Events in the Elderly (ASPREE)', n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm.
RESULTS:
Over a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p<0.01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors.
CONCLUSION:
Aspirin increases overall GI bleeding risk by 60%; however, the 5-year absolute risk of serious bleeding is modest in younger, well individuals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin.
