Users Of Low-dose Acetylsalicylic Acid Research Articles

Influence of IL-β, IL-1RN, and TNF-α variants on the risk of acetylsalicylic acid-induced upper gastrointestinal bleeding: a case-control study.

Forgerini et al. investigated the role of seven genetic variants in the risk of upper gastrointestinal bleeding as an adverse drug reaction. In 289 participants (50 cases and 189 controls), the presence of seven variants in the IL-1β, IL-1RN, and TNF-α genes was not associated with susceptibility to acetylsalicylic acid-induced upper gastrointestinal bleeding. The use of acetylsalicylic acid, even in low doses, may be associated with the onset of upper gastrointestinal bleeding as an idiosyncratic response. Considering the role of the genetic background in inter-individual responses to pharmacotherapy, we aimed to investigate the role of seven variants in the TNF-α, IL-β, and IL-1RN genes in association with the risk of upper gastrointestinal bleeding in users of low-dose acetylsalicylic acid for the prevention of cardiovascular events. A case-control study was conducted in a Brazilian hospital complex. The Case Group comprised patients diagnosed with upper gastrointestinal bleeding who were administered a low dose of acetylsalicylic acid (n=50). Two Control Groups were recruited: 1) low-dose acetylsalicylic acid users without gastrointestinal complaints and under the supervision of a cardiologist (n=50) and 2) healthy controls (n=189). Sociodemographic, clinical, pharmacotherapeutic, and lifestyle data were recorded through face-to-face interviews. Genomic DNA from all participants was genotyped for rs16944 and rs1143634 (IL-β gene), rs4251961 (IL-1RN gene), and rs1799964, rs1799724, rs361525, and rs1800629 (TNF-α gene). No significant difference was noted in the genotypic frequencies of TNF-α, IL-β, and IL-1RN variants between the Case and Control Groups of low-dose acetylsalicylic acid users (p>0.05). The frequency of rs1800629 genotypes (TNF-α gene) differed significantly between the Case Group and healthy controls (p=0.003). None of the evaluated variants were associated with a risk of upper gastrointestinal bleeding. This study aimed to explore pharmacogenomics biomarkers in low-dose acetylsalicylic acid users. Our data suggest that the presence of IL-1β, IL-1RN, and TNF-α variants was not associated with an increased risk of upper gastrointestinal bleeding.

Acetylsalicylic Acid and Mood Disorders: A Systematic Review.

The effects of acetylsalicylic acid (ASA) on mood disorders (MD) and on inflammatory parameters in preclinical and clinical studies have not yet been comprehensively evaluated. The aim of this study was to systematically summarize the available knowledge on this topic according to PRISMA guidelines. Data from preclinical and clinical studies were analyzed, considering the safety and efficacy of ASA in the treatment of MD and the correlation of inflammatory parameters with the effect of ASA treatment. Twenty-one studies were included. Both preclinical and clinical studies found evidence indicating the safety and efficacy of low-dose ASA in the treatment of all types of affective episodes in MD. Observational studies have indicated a reduced risk of all types of affective episodes in chronic low-dose ASA users (HR 0.92, 95% CI: 0.88, 0.95, p < 0.0001). An association between ASA response and inflammatory parameters was found in preclinical studies, but this was not confirmed in clinical trials. Further long-term clinical trials evaluating the safety and efficacy of ASA in recurrent MD, as well as assessing the linkage of ASA treatment with inflammatory phenotype and cytokines, are required. There is also a need for preclinical studies to understand the exact mechanism of action of ASA in MD.

Long-term low-dose acetylsalicylic use shows protective potential for the development of both vascular dementia and Alzheimer’s disease in patients with coronary heart disease but not in other individuals from the general population: results from two large cohort studies

BackgroundNo population-based cohort study investigated a potential inverse association between long-term low-dose acetylsalicylic acid (ASA) use and all-cause dementia and its two most common sub-types Alzheimer’s disease (AD) and vascular dementia (VD) so far.MethodsCox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of low-dose ASA use with all-cause dementia, AD, and VD incidence in community-dwelling older adults from the German ESTHER study (N = 5258) and the UK Biobank (N = 305,394). Inclusion criteria were age of 55 years or older and completed drug assessment. Meta-analyses of the individual participant data from the two prospective cohort studies were performed.ResultsFour hundred seventy-six cases of all-cause dementia, 157 cases of AD, and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5584 participants were diagnosed with all-cause dementia, 2029 with AD, and 1437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (hazard ratio (HR) [95% confidence interval (CI)]: 0.96 [0.93 to 0.99]). The strongest protective effect of low-dose ASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80], 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50], respectively). Furthermore, compared to non-users, users of low-dose ASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56]) whereas no protective associations were observed with shorter low-dose ASA use.ConclusionsThe protective potential of low-dose ASA for all-cause dementia, AD, and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years.

Prescription prevalence of low dose aspirin in primary prevention in the Spanish population, trends over time and associated factors

Background and objectiveThe use of low-dose acetylsalicylic acid (LD-ASA) in primary prevention is a matter of controversy, but its magnitude is unknown in Spain. The aim of the study was to estimate the proportion of patients who are prescribed LD-ASA for primary prevention and to identify their characteristics. MethodsIn a sample from the primary care database BIFAP we obtained the proportion of persons with prescriptions of LD-ASA over the period 2002–2015, excluding patients with any previous record of occlusive vascular disease, atrial fibrillation or cancer. The proportions were standardized to the Spanish population aged 40–99 years old. We identified the factors associated with the use of LD-ASA through a logistic regression and estimated its prevalence of use according to the presence of such factors. ResultsThe sample included 102,850 subjects; of which 6198 were users of LD-ASA. The standardized prevalence of prescription was 2.21% at the start of the period and 3.57% at the end, and increased with age. The factors with the strongest associations were diabetes (OR = 3.26; 95% CI:3.07−3.47), dyslipidaemia (OR = 2.08;1.96−2.21), heart failure (OR = 2.02;1.72−2.37), and hypertension (OR = 1.78;1.67−1.90). Among diabetic patients older than 70 years with hypertension and dyslipidaemia, the prevalence of LD-ASA prescription was 33.7%. ConclusionsThe prescription of LD-ASA for primary prevention in Spain over the study period was low in the general population, but high in older diabetic patients with additional risk factors. After years of controversy, it is time to realign the use of this drug in primary prevention according to recent guidelines.

Prevalencia de prescripción del ácido acetilsalicílico a dosis bajas en prevención primaria en población española, evolución temporal y factores asociados

Background and objectiveThe use of low-dose acetylsalicylic acid (LD-ASA) in primary prevention is a matter of controversy, but its magnitude is unknown in Spain. The aim of the study was to estimate the proportion of patients who are prescribed LD-ASA for primary prevention and to identify their characteristics. MethodsIn a sample from the primary care database BIFAP we obtained the proportion of persons with prescriptions of LD-ASA over the period 2002-2015, excluding patients with any previous record of occlusive vascular disease, atrial fibrillation or cancer. The proportions were standardized to the Spanish population aged 40-99 years old. We identified the factors associated with the use of LD-ASA through a logistic regression and estimated its prevalence of use according to the presence of such factors. ResultsThe sample included 102,850 subjects; of which 6,198 were users of LD-ASA. The standardized prevalence of prescription was 2.21% at the start of the period and 3.57% at the end, and increased with age. The factors with the strongest associations were diabetes (OR=3.26; 95%CI: 3.07-3.47), dyslipidaemia (OR=2.08; 1.96-2.21), heart failure (OR=2.02; 1.72-2.37), and hypertension (OR=1.78; 1.67-1.90). Among diabetic patients older than 70 years with hypertension and dyslipidaemia, the prevalence of LD-ASA prescription was 33.7%. ConclusionsThe prescription of LD-ASA for primary prevention in Spain over the study period was low in the general population, but high in older diabetic patients with additional risk factors. After years of controversy, it is time to realign the use of this drug in primary prevention according to recent guidelines.

The Contribution of Drugs and Helicobacter pylori to Gastric Mucosa Changes in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.

Background The nature and rate of gastric mucosal (GM) damage in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) remain to be among the unsolved problems. Objective To define the role of H. pylori and drugs in the development of GM damages in SLE and APS. Methods A study was conducted on 85 patients with SLE and APS. All the patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucosa of the gastric body and antrum. The presence of H. pylori in the gastric biopsy specimens was determined using polymerase chain reaction. Results Endoscopic examination revealed that the patients with SLE and APS on admission had the following GM changes: antral gastritis (82.4%), erosions (24.7%), hemorrhages (8.2%), and pangastritis (8.2%). SLE and APS patients showed no direct correlation between the found GM damages and the presence of H. pylori. The use of glucocorticoid, low-dose acetylsalicylic acid, nonsteroidal anti-inflammatory drug, and anticoagulant in SLE and APS patients is accompanied by GM damage. Conclusion There was no evidence of the role of H. pylori in GM damage in the SLE and APS patients. More frequent detection of H. pylori was observed in anticoagulants or low-dose acetylsalicylic acid users than in glucocorticoids and nonsteroidal anti-inflammatory drugs ones.

Clinical trial protocol of the ASTER trial: a double-blind, randomized, placebo-controlled phase III trial evaluating the use of acetylsalicylic acid (ASA) for enhanced early detection of colorectal neoplasms

ᅟImmunochemical fecal occult blood tests (iFOBTs) are increasingly used for colorectal cancer (CRC) screening. In our preceding observational study, sensitivity for detecting advanced colorectal neoplasms by iFOBT was 70.8% among users of low-dose acetylsalicylic acid compared with 35.9% among non-users (p = 0.001), whereas there were only very small differences in specificity. In receiver operating characteristics (ROC) analyses, the area under the curve (AUC) was much higher for acetylsalicylic acid users than for non-users, with particularly strong differences in men (0.87 versus 0.68, p = 0.003). These findings suggested that use of acetylsalicylic acid before conduct of iFOBT might be a promising approach to improve non-invasive screening for CRC.Methods/designIn this randomized, double-blind, placebo-controlled trial, the diagnostic performance of two iFOBTs for detecting advanced colorectal neoplasms after a single low-dose of acetylsalicylic acid (300 mg) compared to placebo is evaluated. Acetylsalicylic acid or placebo is administered at least 5 days before a planned, study-independent colonoscopic screening in 2400 participants aged 40 to 80 years. Stool samples are obtained before and on three different days after the single dose of acetylsalicylic acid or placebo. In addition, optional blood samples are taken for future biomarker analyses. The diagnostic performance of the iFOBTs will be compared to the results of the colonoscopy as a gold standard for the diagnosis of colorectal neoplasms. Additionally, gender-specific performance of the tests and gain in diagnostic performance by test application on multiple days will be evaluated.DiscussionIf the findings from our preceding observational study will be confirmed in this large trial, the proposed low-risk, inexpensive intervention would considerably improve the diagnostic accuracy of iFOBTs and thus lead to enhanced early detection of colorectal neoplasms. Thus, the results of this trial may have a large public health impact.Trial registrationThis trial was registered before recruitment of the participants in www.clinicaltrialsregister.eu on the 30th of May 2012: EudraCT No.: 2011–005603-32 and in www.drks.de on 13th of March 2012: German Clinical Trials Register DRKS-ID: DRKS00003252.

Cost Effectiveness of Gastroprotection with Proton Pump Inhibitors in Older Low-Dose Acetylsalicylic Acid Users in the Netherlands.

PurposeThe present study aimed to assess the cost effectiveness of concomitant proton pump inhibitor (PPI) treatment in low-dose acetylsalicylic acid (LDASA) users at risk of upper gastrointestinal (UGI) adverse effects as compared with no PPI co-medication with attention to the age-dependent influence of PPI-induced adverse effects.MethodsWe used a Markov model to compare the strategy of PPI co-medication with no PPI co-medication in older LDASA users at risk of UGI adverse effects. As PPIs reduce the risk of UGI bleeding and dyspepsia, these risk factors were modelled together with PPI adverse effects for LDASA users 60–69, 70–79 (base case) and 80 years and older. Incremental cost-utility ratios (ICURs) were calculated as cost per quality-adjusted life-year (QALY) gained per age category. Furthermore, a budget impact analysis assessed the expected changes in expenditure of the Dutch healthcare system following the adoption of PPI co-treatment in all LDASA users potentially at risk of UGI adverse effects.ResultsPPI co-treatment of 70- to 79-year-old LDASA users, as compared with no PPI, resulted in incremental costs of €100.51 at incremental effects of 0.007 QALYs with an ICUR of €14,671/QALY. ICURs for 60- to 69-year-old LDASA users were €13,264/QALY and €64,121/QALY for patients 80 years and older. Initiation of PPI co-treatment for all Dutch LDASA users of 60 years and older at risk of UGI adverse effects but not prescribed a PPI (19%) would have cost €1,280,478 in the first year (year 2013 values).ConclusionsPPI co-medication in LDASA users at risk of UGI adverse effects is generally cost effective. However, this strategy becomes less cost effective with higher age, particularly in patients aged 80 years and older, mainly due to the increased risks of PPI-induced adverse effects.

Incidence and Predictors of Hemorrhagic Stroke in Users of Low-Dose Acetylsalicylic Acid

The use of antithrombotic drugs (anticoagulants and antiplatelet drugs) has been reported to increase the risk of hemorrhagic stroke (HS) relative to no treatment. This study was performed to characterize the incidence and predictors of HS in users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. A cohort of 36,775 ASA users aged 50-84 years in 2000-2007 was identified from The Health Improvement Network database. The incidence of HS was calculated, and a nested case-control analysis, adjusted for potential confounding factors, was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association of potential risk factors with HS in current users of ASA. The overall incidence of HS was 5.70 cases per 10,000 person-years and increased with age. In current ASA users, the incidence of HS was 4.91 cases per 10,000 person-years. Predictors of HS in patients taking ASA for secondary prevention included a history of HS (OR, 4.84; 95% CI, 1.48-15.88), a history of atrial fibrillation (OR, 4.03; 95% CI, 1.53-10.62), and hypnotic/anxiolytic drug use (OR, 2.67; 95% CI, 1.17-6.05). The small number of patients using warfarin also had an increased risk of HS (OR, 23.42; 95% CI, 4.89-112.10). Physicians should consider additional risk factors for HS, such as a history of HS or atrial fibrillation, and the use of warfarin, before prescribing ASA for the secondary prevention of cardiovascular events.

Risk of uncomplicated peptic ulcer disease in a cohort of new users of low-dose acetylsalicylic acid for secondary prevention of cardiovascular events.

BackgroundThe aim of this study was to analyse the risk of uncomplicated peptic ulcer disease (PUD) in a cohort of new users of low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular events in a UK primary care setting.MethodsNew users of low-dose ASA for secondary prevention of cardiovascular events, aged 50-84 years in 2000-2007, were identified from The Health Improvement Network. Among those 38,975 individuals, 309 patients were considered to be incident cases of uncomplicated PUD. Incidence of uncomplicated PUD was calculated and a nested case–control analysis adjusted for potential confounding factors was performed to calculate the odds ratios (ORs) for the association of potential risk factors with uncomplicated PUD.ResultsThe crude incidence of uncomplicated PUD was 1.41 per 1000 person-years (95% confidence interval [CI], 1.26-1.58). Individuals with a history of PUD were more likely to develop uncomplicated PUD than those without such a history (hazard ratio [HR], 2.22, 95% CI, 1.60-3.09). In nested case–control analyses, the risk of uncomplicated PUD was associated with current use of non-steroidal anti-inflammatory drugs, oral steroids or acid suppressants. Other risk factors for developing uncomplicated PUD included smoking, stress, depression, anaemia and social deprivation.ConclusionOur results indicate that several risk factors significantly increase the risk of development of uncomplicated PUD in new users of low-dose ASA. Therefore, physicians should monitor ASA users for gastrointestinal symptoms and signs of ulcer, particularly if they have additional risk factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-014-0205-y) contains supplementary material, which is available to authorized users.

Use of proton pump inhibitors and the risk of coronary events in new users of low-dose acetylsalicylic acid in UK primary care

This study evaluated the risk of cardiovascular events associated with the use of proton pump inhibitors (PPIs) in new users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Two cohorts of patients aged 50-84 years were identified from UK primary care databases: individuals with a first prescription for ASA (75-300 mg/day) for secondary prevention of cardiovascular events (n = 39,513; CVD cohort) or with a record of hospitalisation for an acute coronary event (n = 42,542; ACS cohort) in 2000-2007. Cases of non-fatal myocardial infarction (MI) and coronary death were identified: 1,222 in the CVD cohort and 604 among new users of ASA in the ACS cohort. A nested case-control analysis estimated the relative risk (RR) of non-fatal MI or coronary death associated with use vs non-use of PPI therapy. Current continuous use of PPI therapy was not associated with a significant increase in RR overall: in the CVD cohort (RR=1.14 [95% confidence interval = 0.91-1.43]); in the ACS cohort (0.88 [0.66-1.18]); or among current continuous users of ASA as antiplatelet monotherapy (CVD cohort: 1.15 [0.80-1.66]; ACS cohort: 0.73 [0.43-1.23]; pooled analysis of both cohorts: 0.96 [0.62-1.48]). Inconclusion, among first-time users of ASA for the secondary prevention of cardiovascular events, PPI use was not shown to be associated with an increased risk of non-fatal MI or coronary death.

Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER* study

ObjectivesTo evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia.MethodsIn this...

Low‐dose acetylsalicylic acid and gastrointestinal ulcers or bleeding – a cohort study of the effects of proton pump inhibitor use patterns

The aim of this study was to investigate the associations between proton pump inhibitor (PPI) usage patterns and risk of severe gastrointestinal events in patients treated with low-dose acetylsalicylic acid (LDA). A nationwide cohort study in Sweden. All Swedish residents ≥ 40 years of age, without cancer and receiving LDA treatment (≥ 80% adherence for 365 days between 2005 and 2009) were identified in the Swedish Prescription Register. Continuous PPI use was defined as > 60 of 90 days covered by daily PPI doses and further divided into high (≥ 80%) or moderate (< 80) adherence. All other PPI use was defined as intermittent use. The risk of a combined end-point of gastrointestinal ulcer or bleeding was analysed using Cox proportional hazard models. We also investigated risk of > 45 days of LDA treatment interruption. During a median follow-up of 2.5 years, 7880 of 648,807 (1.2%) LDA-treated patients experienced gastrointestinal events. In multivariable-adjusted models, both intermittent-PPI and no-PPI use were associated with increased risk of gastrointestinal ulcers or bleeding compared with continuous PPI use with a high level of adherence [hazard ratio (HR) 1.83 (95% CI 1.66-2.02) and 1.14 (95% CI 1.05-1.23), respectively]. Amongst continuous PPI users, moderate adherence also increased the risk of gastrointestinal ulcers or bleeding [HR 1.22 (95% CI 1.07-1.40)]. The risk of LDA treatment interruption was higher with intermittent PPI use [HR 1.16 (95% CI 1.14-1.19)] than continuous PPI use with high adherence. In this large cohort of LDA users, intermittent PPI use was associated with higher risk of gastrointestinal ulcers or bleeding and interrupted LDA treatment, compared with continuous PPI use.

Su1031 Incidence of Uncomplicated Symptomatic Peptic Ulcer in Patients Receiving Low-Dose Acetylsalicylic Acid for Secondary Prevention of Cardiovascular Events

Introduction. In the general population, the incidence of uncomplicated peptic ulcer (PU) has been estimated at 0.75 per 1000 person-years.1 An incidence of 1.1 per 1000 personyears has been reported for upper gastrointestinal bleeding, including PU bleeding, in patients receiving low-dose acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular (CV) events.2 However, few studies have investigated the incidence of uncomplicated PU in such patients; the present analysis addresses this question. Methods. Data were collected from The Health Improvement Network, a UK primary care database. Patients analyzed were aged 50-84 years and received a first prescription of low-dose ASA, for the secondary prevention of CV events, between January 2000 and December 2007 (N=38 975). Patients were followed up from the start date (first ASA prescription) until they received a diagnosis of uncomplicated PU, met an exclusion criterion, or until the end of the study period (September 2011). The computerized profiles of potential ulcer cases (n=555) were manually reviewed, including free text comments, to classify them as definite cases (n=337), possible cases (n=20) and non-cases (including unconfirmed events and complicated PU; n=198). We calculated the incidence rate of uncomplicated PU overall and by baseline characteristics at the start date. A Nelson-Aalen time-to-event analysis was performed to estimate the cumulative proportion of patients who would develop uncomplicated PU during a mean follow-up of 5.6 years. Results. In the total study cohort, 357 cases of uncomplicated PU were confirmed following the review process. The overall incidence of uncomplicated PU was 1.63 (95% confidence interval [CI], 1.47-1.81) per 1000 person-years. The incidence rate was similar in men and women, but was higher in older than in younger patients, ranging from 1.29 (95% CI, 1.01-1.63) per 1000 person-years in patients aged 50-59 years to 2.66 (95% CI, 1.83-3.88) per 1000 person-years in those aged 80 years or over. A higher incidence of uncomplicated PU was observed in new users of ASA with a history of PU disease (3.86 per 1000 person-years, 95% CI, 2.97-5.02) than in those without (1.47 per 1000 person-years, 95% CI, 1.32-1.65). A history of PU disease was also associated with an increased probability of developing uncomplicated PU in a time-to-event analysis (p,0.0001; Figure 1). Conclusions. Each year, uncomplicated PU may develop in approximately 2 per 1000 users of low-dose ASA for the secondary prevention of cardiovascular events. An age of 80 years or over or a history of PU disease increased the annual incidence to almost 3 patients per 1000 or approximately 4 patients per 1000, respectively. Reference 1. Cai S et al. Aliment Pharmacol Ther 2009;30:1039-48. 2. Cea Soriano L, Garcia Rodriguez LA. Front Pharmacol 2010;1:126.

Esomeprazole for Prevention and Resolution of Upper Gastrointestinal Symptoms in Patients Treated With Low-dose Acetylsalicylic Acid for Cardiovascular Protection

Although low-dose acetylsalicylic acid (ASA) is recommended for prevention of cardiovascular events in at-risk patients, its long-term use can be associated with the risk of peptic ulcer and upper gastrointestinal (GI) symptoms that may impact treatment compliance. This prespecified secondary analysis of the OBERON study (NCT00441727) determined the efficacy of esomeprazole for prevention/resolution of low-dose ASA-associated upper GI symptoms. A post hoc analysis of predictors of symptom prevention/resolution was also conducted. Helicobacter pylori-negative patients taking low-dose ASA (75-325 mg) for cardiovascular protection who had ≥1 upper GI risk factor were eligible. The patients were randomized to once-daily esomeprazole 40 mg, 20 mg, or placebo, for 26 weeks; 2303 patients (mean age 67.6 years; 36% aged >70 years) were evaluable for upper GI symptoms. The proportion of patients with dyspeptic or reflux symptoms (self-reported Reflux Disease Questionnaire) was significantly lower (P < 0.0001) in those treated with esomeprazole versus in those treated with placebo. Treatment with esomeprazole (P < 0.0001), age >70 years (P < 0.01), and the absence of upper GI symptoms at baseline (P < 0.0001) were all factors associated with prevention/resolution of upper GI symptoms. Together, these analyses demonstrate that esomeprazole is effective in preventing and resolving patient-reported upper GI symptoms in low-dose ASA users at increased GI risk.

Reducing the risk of gastroduodenal ulcers with a fixed combination of esomeprazole and low-dose acetyl salicylic acid

Low-dose acetyl salicylic acid (ASA) for preventing cardiovascular and cerebrovascular events is now one of the most frequently prescribed medications in some Western countries. However, it is associated with significant morbidity and mortality as a consequence of the development of gastric and duodenal ulcers and their complications. Recent randomized controlled trials in patients who are at moderately increased risk of ulcers have shown that the proton pump inhibitor esomeprazole (the S-isomer of racemic omeprazole) reduces the gastroduodenal ulcer incidence by approximately 70–85% and the gastrointestinal bleeding risk by as much as 90%. Case–control studies also indicate that the risk of ulcer bleeding is less in low-dose ASA users who concomitantly take a proton pump inhibitor. This article reviews the pharmacology of the component agents and the evidence for efficacy of the combination of esomeprazole and low-dose ASA.

Risk of Upper Gastrointestinal Bleeding With Low-Dose Acetylsalicylic Acid Alone and in Combination With Clopidogrel and Other Medications

This study evaluated the risk of upper gastrointestinal bleeding (UGIB) associated with use of low-dose acetylsalicylic acid (ASA) alone and in combination with other gastrotoxic medications. The Health Improvement Network UK primary care database was used to identify individuals 40 to 84 years of age with a UGIB diagnosis in 2000 to 2007 (n = 2049). An age-, sex-, and calendar year-matched control group (n = 20,000) was identified from the same source population. The relative risk (RR) of UGIB associated with use of low-dose ASA (75 to 300 mg/d), clopidogrel, and other commonly coadministered medications was estimated by multivariate logistic regression. The risk of UGIB was increased in current users of low-dose ASA (RR, 1.80; 95% confidence interval [CI], 1.59 to 2.03) or clopidogrel (RR, 1.67; 95% CI, 1.24 to 2.24) compared with nonusers. Compared with low-dose ASA monotherapy, the risk of UGIB was significantly increased when low-dose ASA was coadministered with clopidogrel (RR, 2.08; 95% CI, 1.34 to 3.21), oral anticoagulants (RR, 2.00; 95% CI, 1.15 to 3.45), low-/medium-dose nonsteroidal antiinflammatory drugs (RR, 2.63; 95% CI, 1.93 to 3.60), high-dose nonsteroidal antiinflammatory drugs (RR, 2.66; 95% CI, 1.88 to 3.76), or high-dose oral corticosteroids (RR, 4.43; 95% CI, 2.10 to 9.34); this was not apparent with coadministration of statins (RR, 0.99; 95% CI, 0.81 to 1.21) or low-dose oral corticosteroids (RR, 1.01; 95% CI, 0.58 to 1.77). Use of low-dose ASA is associated with an almost 2-fold increase in the risk of UGIB compared with nonuse. This risk is increased further in individuals taking low-dose ASA along with clopidogrel, oral anticoagulants, nonsteroidal antiinflammatory drugs, or high-dose oral corticosteroids.

Increased risk of stroke after discontinuation of acetylsalicylic acid

Discontinuation of low-dose acetylsalicylic acid (ASA) therapy may increase the risk of ischemic events. This study evaluated the risk of ischemic stroke (IS) and TIA after low-dose ASA discontinuation in patients with cardiovascular disease or cerebrovascular disease. The Health Improvement Network UK primary care database was used to identify a cohort of individuals aged 50-84 years with a first prescription for low-dose ASA (75-300 mg/day) for the secondary prevention of cardiovascular or cerebrovascular events in 2000-2007 (n = 39,512). Individuals were followed up for a mean of 3.4 years to identify cases of IS/TIA. Nested case-control analyses were used to assess risk factors for IS/TIA, including low-dose ASA discontinuation. The overall incidence of IS/TIA was 5.0 per 1,000 person-years (95% confidence interval [CI] 4.6-5.4). IS/TIA was significantly more common in patients with a previous diagnosis of cerebrovascular disease (relative risk [RR] 2.79; 95% CI 2.05-3.80) or atrial fibrillation (RR 1.71; 95% CI 1.28-2.29) than in those without these conditions. Compared with current users of low-dose ASA, those who discontinued treatment 31-180 days before the index date had a significantly increased overall risk of IS/TIA (RR 1.40; 95% CI 1.03-1.92). The most common reason for discontinuation was patient nonadherence. In patients prescribed low-dose ASA for the secondary prevention of cardiovascular or cerebrovascular events, discontinuation of low-dose ASA was associated with a 40% increase in the risk of IS/TIA compared with continuation of therapy. This study provides Class III evidence that discontinuation of low-dose ASA is associated with a 40% increased risk of stroke within 31-180 days of discontinuation.

T1050 Dyspeptic Symptoms and Sleep Disturbance: A Report from a Large Observational Study in Low-Dose Acetylsalicylic Acid Users

T1050 Dyspeptic Symptoms and Sleep Disturbance: A Report from a Large Observational Study in Low-Dose Acetylsalicylic Acid Users

The higher oxides of copper

<h3>Abstract</h3> <h3>Objectives</h3> To investigate the association between long term low-dose acetylsalicylic acid (LDASA) use and the development of all-cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD). <h3>Design</h3> Meta-analysis of individual participant data from two prospective cohort studies. <h3>Setting</h3> Community-dwelling older adults from Germany (ESTHER) and United Kingdom (UK Biobank). <h3>Participants</h3> 5,258 ESTHER and 305,394 UK Biobank participants who were 55 years or older and completed drug assessment were included for analysis. <h3>Main outcome measures</h3> Cox regression models with inverse probability of treatment weighting to model the underlying cardiovascular risk were used to assess the associations of LDASA use with all-cause dementia, AD and VD incidence. <h3>Results</h3> 476 cases of all-cause dementia, 157 cases of AD and 183 cases of VD were diagnosed over a median of 14.3 years of follow-up in ESTHER. In the UK Biobank, 5,584 participants were diagnosed with all-cause dementia, 2,029 with AD and 1,437 with VD over a median of 11.6 years. The meta-analysis of both cohorts revealed a weak reduction in hazards for all-cause dementia (HR [95% CI]: 0.96 [0.93 to 0.99]). The strongest protective effect of LDASA was observed in participants with coronary heart disease (CHD) in both cohorts, and a significant interaction was detected. In particular, in meta-analysis, a 31% reduction in hazard for AD, 69% for VD and 34% for all-cause dementia were observed (HR [95% CI]: 0.69 [0.59 to 0.80], 0.31 [0.27 to 0.35], 0.46 [0.42 to 0.50], respectively). Furthermore, compared to non-users, users of LDASA for 10 years or longer (who likely use it because they have CHD or a related diagnosis putting them at an increased risk for cardiovascular events) demonstrated a strong protective effect on all dementia outcomes, especially for VD (HR [95% CI]: 0.48 [0.42 to 0.56]) whereas no protective associations were observed with shorter LDASA use. <h3>Conclusions</h3> The protective potential of LDASA for all-cause dementia, AD and VD seems to strongly depend on pre-existing CHD and the willingness of patients to take it for a minimum of ten years.