Long-term Aspirin Research Articles

BIOBOARD

ASIA – Gene mutation discovered to cause severe growth retardation in newly discovered disease. ASIA – Singapore scientists make major breakthrough to treat fibrotic diseases that cause organ impairment and failure. ASIA – DcR3 is the key factor of endometriosis. ASIA – Singapore Volition signs MOU with National Taiwan University to conduct two large clinical studies. EUROPE & CIS – NPL relaunches to accelerate access to new health innovations. EUROPE & CIS – The hard truth about Eczema: It’s something in the water. EUROPE & CIS – Gastric acid suppressant lansoprazole may target tuberculosis. EUROPE & CIS – Long-term aspirin use reduces incidence of digestive cancers by up to 47 per cent. AMERICAS – Rockefeller University biologist Michael W. Young honored with Nobel Prize for pioneering studies on circadian rhythm. AMERICAS – Ohio physicians contribute to groundbreaking stroke research. AMERICAS – A poorly explored immune cell may impact cancer immunity and immunotherapy. AMERICAS – Superbugs have a new foe. AMERICAS – Approved drug or herbal treatment: How to choose?

Mid-aortic syndrome secondary to Takayasu’s disease

A 24-year-old young woman with good past health presented with hypertension during body check. Blood erythrocyte sedimentary rate level was elevated. CT and MR angiography revealed moderate stenosis of abdominal...

Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer

Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer. We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts. The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer

The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95% CI: 0.06–0.41, p = 0.0002), but was less effective in reversing the methylation that occurred in IM. Frequent hypermethylation including that of CDH1 in AM increased in the GC group compared to the AG group, and CDH1 methylation was an independent predictive marker of GC (OR: 8.50, 95% CI: 2.64–25.33, p = 0.0003). In patients with long-term aspirin use, the changes of molecular events in AM but not IM may be an important factor in the reduction of cancer incidence. In addition, methylation of the CDH1 gene in AM may be a surrogate of GC.

Safety and Necessity of Antiplatelet Therapy on Patients Underwent Endovascular Aortic Repair with Both Stanford Type B Aortic Dissection and Coronary Heart Disease.

Background:Acute aortic dissection is known as the most dangerous aortic disease, with management and prognosis determined as the disruption of the medial layer provoked by intramural bleeding. The objective of this study was to evaluate the safety and necessity of antiplatelet therapy on patients with Stanford Type B aortic dissection (TBAD) who underwent endovascular aortic repair (EVAR).Methods:The present study retrospectively analyzed 388 patients with TBAD who underwent EVAR and coronary angiography. The primary outcomes were hemorrhage, death, endoleak, recurrent dissection, myocardial infarction, and cerebral infarction in patients with and without aspirin antiplatelet therapy at 1 month and 12 months.Results:Of those 388 patients, 139 (35.8%) patients were treated with aspirin and 249 (64.2%) patients were not treated with aspirin. Patients in the aspirin group were elderly (57.0 ± 10.3 years vs. 52.5 ± 11.9 years, respectively, χ2 = 3.812, P < 0.001) and had more hypertension (92.1% vs. 83.9%, respectively, χ2 = 5.191, P = 0.023) and diabetes (7.2% vs. 2.8%, respectively, χ2 = 4.090, P = 0.043) than in the no-aspirin group. Twelve patients (aspirin group vs. no-aspirin group; 3.6% vs. 2.8%, respectively, χ2 = 0.184, P = 0.668) died at 1-month follow-up, while the number was 18 (4.6% vs. 5.0%, respectively, χ2 = 0.027, P = 0.870) at 12-month follow-up. Hemorrhage occurred in 1 patient (Bleeding Academic Research Consortium [BARC] Type 2) of the aspirin group, and 3 patients (1 BARC Type 2 and 2 BARC Type 5) in the no-aspirin group at 1-month follow-up (χ2 = 0.005, P = 0.944). New hemorrhage occurred in five patients in the no-aspirin group at 12-month follow-up. Three patients in the aspirin group while five patients in the no-aspirin group had recurrent dissection for endoleak at 1-month follow-up (2.3% vs. 2.2%, respectively, χ2 = 0.074, P = 0.816). Four patients had new dissection in the no-aspirin group at 12-month follow-up (2.3% vs. 3.8%, respectively, χ2 = 0.194, P = 0.660). Each group had one patient with myocardial infarction at 1-month follow-up (0.8% vs. 0.4%, respectively, χ2 = 0.102, P = 0.749) and one more patient in the no-aspirin group at 12-month follow-up. No one had cerebral infarction in both groups during the 12-month follow-up. In the percutaneous coronary intervention (PCI) subgroup, 44 (31.7%) patients had taken dual-antiplatelet therapy (DAPT, aspirin + clopidogrel) and the other 95 (68.3%) patients had taken only aspirin. There was no significant difference in hemorrhage (0% vs. 1.1%, respectively, χ2 = 0.144, P = 0.704), death (4.8% vs. 4.5%, respectively, χ2 = 0.154, P = 0.695), myocardial infarction (2.4% vs. 0%, respectively, χ2 = 0.144, P = 0.704), endoleak, and recurrent dissection (0% vs. 3.4%, respectively, χ2 = 0.344, P = 0.558) between the two groups at 12-month follow-up.Conclusions:The present study indicated that long-term oral low-dose aspirin was safe for patients with both TBAD and coronary heart disease who underwent EVAR. For the patients who underwent both EVAR and PCI, DAPT also showed no increase in hemorrhage, endoleak, recurrent dissection, death, and myocardial infarction.

Long-term aspirin does not lower risk of stroke and increases bleeding risk in low-risk atrial fibrillation ablation patients.

Stroke risk is a significant concern in patients with atrial fibrillation (AF). Low stroke risk patients (CHADS2 VASc 0-2) are often treated long-term with aspirin after catheter ablation. Defining the long-term risks versus benefits of aspirin therapy, after an ablation, is essential to validate this common clinical approach. A total of 4,124 AF ablation patients undergoing their index ablation were included in this retrospective observational study. We compared 1- and 3-year outcomes for cerebrovascular accident (CVA), transient ischemic attack (TIA), gastrointestinal (GI) bleeding, genitourinary (GU) bleeding, any bleeding, and AF recurrence among patients receiving: none, aspirin, or warfarin as long-term therapies. Patient distribution by CHADS2 VASc scores was as follows: 0: 1,143 (28%), 1: 1,588 (39%), and 2: 1,393 (34%). Significantly higher incidents of: female gender, hypertension, diabetes mellitus, heart failure, and vascular disease were seen with higher CHADS2 VASc scores (P<0.0001 for all). At 3 years, 238 (5.9%) patients were on warfarin, 743 (18.6) on aspirin, and 3,013 (75.5%) on no therapy; with occurrences of CVA/TIA (1.4%, 3.0%, 3.9%, P<0.0001, respectively), GI bleeding (0.8%, 1.9%, 1.1%, P=0.06, respectively), and GU bleeding (1.7%, 2.8%, 2.1%, P=0.008, respectively) that increased with advancing CHA2 DS2 VASc score. There was a significantly increased risk for both CVA/TIA with aspirin therapy, when compared to no therapy or warfarin therapy in general, and across all CHA2 DS2 VASc scores. After catheter ablation, low risk patients do not benefit from long-term aspirin therapy, but are at risk for higher rates of bleeding when compared to no therapy or warfarin.

Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.

Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials.

Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.

Upper Gastrointestinal Complications and Cardiovascular/Gastrointestinal Risk Calculator in Patients with Myocardial Infarction Treated with Aspirin.

Background:Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator.Methods:The MI patients who visited Shapingba District People's Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events.Results:A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774–0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93.1%, respectively, for predicting gastrointestinal events in Chinese patients with MI.Conclusions:AsaRiskCalculator had a predictive value for gastrointestinal events in Chinese patients with MI. HP infection seemed to be an independent risk factor for gastrointestinal events caused by long-term aspirin treatment in Chinese patients with MI, and it should be included in the risk calculator adapted for Chinese patients.

Effect of Low-Dose Aspirin on Bleeding Following Exodontia: A Prospective Clinical Study

This research aims to study the effects of low-dose aspirin on bleeding after exodontia and to compare statistically and analyze perioperative blood loss during exodontia in patients on aspirin therapy and healthy patients and also to discuss the various measures if required necessary for controlling postoperative bleeding in simple and uncomplicated exodontia. The study included 100 patients, ranging in age from 30 to 60years. The patients were divided into two groups, a test group consisting of 50 patients who were on a daily dose of 75-150mg of aspirin and a control group consisting of 50 patients not on any antiplatelet therapy. All extraction procedures were performed on outpatient basis. Patients were operated under local anesthesia. Post-extraction sockets were checked for bleeding immediately (30min) and followed up at 24, 48, and 72h, and 1week, after the procedure. Amount of intraoperative blood loss was similar in both test and control groups, and there was no excessive postoperative bleeding in any case. Out of 100 patients, only three patients of test group and two patients of control group required level II hemostatic measures and two patients of test group needed level III measures. We could reach a conclusion and recommend that patients on long-term low-dose aspirin (75-150mg) need not to discontinue their aspirin dose prior to routine exodontia and can be carried out safely with enhanced local hemostatic measures, if required.

Aspirin Before Elective Surgery-Stop or Continue?

Cessation of long-term aspirin treatment before noncardiac surgery can cause adverse cardiac events in patients at risk, particularly in those with previous percutaneous coronary interventions (PCI) with stent implantation. The factors influencing the clinical decision to stop aspirin treatment are currently unknown. In a single-center, cross-sectional study (retrospective registration: NCT03049566) carried out from February to December 2014, we took a survey among patients scheduled for noncardiac surgery who were under long-term aspirin treatment, and among their treating anesthesiologists using standardized questionnaires on preoperative aspirin use, comorbidities, and risk-benefit assessments. The main objective was to identify factors associated with the decision to stop aspirin treatment. The results of multivariable logistic regressions and intraclass correlations are presented. 805 patients were included in the study, and 636 questionnaires were returned (203 of which concerned patients with coronary stents). 46.8% of the patients stopped their long-term aspirin treatment before surgery; 38.7% of these patients stopped it too early (>10 days before surgery) or too late (≤ 3 days before surgery). A prior PCI with stent implantation lowered the probability of aspirin cessation (odds ratio [OR] = 0.47 [0.31; 0.72]; p <0.001). On the other hand, patients were more likely to stop their long-term aspirin treatment if it had already been discontinued once before (OR = 4.58 [3.06; 6.84]; p <0.001), if there was a risk of bleeding into a closed space (OR = 4.54 [2.02; 10.22]; p <0.001), if they did not know why they were supposed to take aspirin (OR = 2.12 [1.05; 4.28]; p = 0.036), or if the preoperative consultation with the anesthesiologist occurred <2 days before surgery (OR = 1.60 [1.08; 2.37]; p = 0.018). Patients often assessed the risks related to aspirin cessation lower than their physicians did. This study reveals discordance between guideline recommendations and everyday clinical practice in patients with coronary stents. The early integration of cardiologists and anesthesiologists and a more widespread use of stent implant cards could promote adherence to the guidelines.

Abstract 3012: Long-term aspirin use and total and cancer-specific mortality

Abstract Background: Long-term follow of clinical trials of aspirin for the prevention of cardiovascular disease have shown that aspirin may be associated with a reduced risk of death from cancer, including colorectal, esophageal, and lung cancer, and possibly breast and prostate cancer. However, the potential benefits of aspirin use, at a range of doses and duration of use, on total and cancer-specific mortality have not been examined in large prospective cohort studies with long-term follow-up. Methods: We examined the association between aspirin use and subsequent total and cancer-specific mortality, at a range of doses and duration of use, among 86,206 women in the Nurses' Health Study (1980-2012) and 43,977 men in the Health Professionals Follow-up Study (1986-2012). Participants with a history of cancer, heart disease, or stroke were excluded. Aspirin use was assessed at baseline and updated every 2 years with greater than 90% follow-up. Cox proportional hazards models were used to compute hazard ratios as estimates for age- and multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). Results: During up to 32 years of follow-up, 22,094 women and 14,749 men died, and 8,271 women and 4,591 men died of cancer. Compared with nonregular use, regular aspirin use was associated with lower risk of total mortality (multivariable-adjusted RR 0.93; 95% CI 0.90-0.95 for women and RR 0.89; 95% CI 0.86-0.93 for men), which was primarily due to a lower risk of dying from any cancer (RR 0.93; 95% CI 0.89-0.97 for women and RR 0.85; 95% CI 0.80-0.90 for men), especially colorectal cancers (RR 0.69; 95% CI 0.59-0.81 for women and RR 0.70; 95% CI 0.57-0.85 for men), breast cancers (RR 0.89; 95% CI 0.79-0.99), prostate cancers (RR 0.77; 95% CI 0.65-0.90), and lung cancers in men (RR 0.86; 95% CI 0.74-0.99). The benefit of aspirin on cancer mortality appeared evident with use of at least 0.5 to 1.5 standard aspirin tablets per week for both men and women; and the minimum duration of regular use associated with lower cancer mortality was 6 years. Conclusions: Long-term aspirin use was associated with reduced risk of total mortality, primary due to reduced risk of dying from cancers. Citation Format: Yin Cao, Meir Stampfer, Walter Willett, Donna Spiegelman, JoAnn Manson, Eric Rimm, Molin Wang, Shuji Ogino, Charles Fuchs, Edward Giovannucci, Andrew Chan. Long-term aspirin use and total and cancer-specific mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3012. doi:10.1158/1538-7445.AM2017-3012

The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy

BackgroundPreventive strategies developed to avoid the complications of antiplatelet therapies recommend the evaluation of risk factors for gastrointestinal events and indicated gastroprotective strategies. AimWe aimed to assess the impact of predisposing factors - histological findings, concomitant drug consumption, comorbidities, symptoms, social habits, Helicobacter pylori infection - on severe gastro-duodenal lesions in patients with low-dose aspirin and concomitant protective therapy with proton pump inhibitors (PPI). MethodWe enrolled 237 patients with LDA and PPI therapy, referred for upper digestive endoscopy, divided into two groups according to the severity of their endoscopic lesions (172 patients with no or mild endoscopic lesions and 65 patients with severe endoscopic lesions). ResultsIn the univariate logistic regression model, the factors associated with severe gastro-duodenal lesions were gender (OR=1.87, 95% CI: 1.04–3.41), anticoagulants (OR=2.40, 95% CI: 1.26–4.53), gastric atrophy and/or intestinal metaplasia (OR=1.85, 95% CI: 1.04–3.32), congestive heart failure (OR=2.59, 95% CI: 1.16–6.62), anaemia (OR=3.01, 95% CI: 1.67–5.47) and smoking (OR=4.29, 95% CI: 1.57–12.32). In the final model, anticoagulants (p=0.041<0.05) and anaemia (p=0.019<0.05) were risk factors for severe lesions via multivariate regression analysis, while for active/inactive chronic gastritis and smoking a positive dependency with a tendency towards statistical significance (p<0.10) was noticed for severe gastric lesions. ConclusionsIn patients treated with low-dose aspirin and gastroprotective therapy with proton pump inhibitors we have enough evidence to consider co-treatment with anticoagulants and anaemia important predictors for severe endoscopic lesions, while other factors such as inflammation in gastric biopsies, congestive heart failure, co-treatment with clopidogrel and smoking tended to have a positive influence on risk for severe gastro-duodenal lesions.

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men.

Background: Men of African descent experience a disproportionately high prostate cancer mortality. Intratumoral inflammation was found to be associated with aggressive prostate cancer. We and others have shown that prostate tumors in African-American (AA) patients harbor a distinct immune and inflammation signature when compared with European-American (EA) patients. These observations suggest that inflammation could be a driver of aggressive disease in men of African descent, leading to the hypothesis that an anti-inflammatory drug like aspirin could prevent disease progression.Methods: We examined the relationship between aspirin use and prostate cancer in the NCI-Maryland Prostate Cancer Case-Control Study consisting of 823 men with incident prostate cancer (422 AA and 401 EA) and 1,034 population-based men without the disease diagnosis (486 AA and 548 EA).Results: We observed a significant inverse association between regular aspirin use and prostate cancer among AA men. Stratification of AA patients by disease stage showed that daily and long-term (>3 years) aspirin use significantly decreased the risk of advanced disease [adjusted ORs for T3/T4 disease: 0.35, 95% confidence interval (CI), 0.17-0.73; and 0.22, 95% CI, 0.08-0.60, respectively], but not early-stage disease (T1/T2). Regular aspirin use also reduced disease recurrence in AA men.Conclusions: Regular aspirin use is associated with a decreased risk of advanced stage prostate cancer and increased disease-free survival in AA men.Impact: Regular aspirin use before and after a prostate cancer diagnosis may prevent the development of aggressive disease in AA men who are at risk of a lethal malignancy. Cancer Epidemiol Biomarkers Prev; 26(6); 845-53. ©2017 AACR.

Long-Term Aspirin Use Reduces Cancer Mortality &amp; Risk of Developing Cancer

Long-Term Aspirin Use Reduces Cancer Mortality &amp; Risk of Developing Cancer

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE. Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE. For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE. Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Aspirin and Risk of Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P=0.99). We found a significant association between short-term use of aspirin (<3 months) and the risk of aSAH (odds ratio, 1.61; 95% confidence interval, 1.20-2.18; P=0.002). No significant difference was found in terms of risk of aSAH for 3 to 12 months, 1 to 3 years, and >3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (<3 months) use of aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial.

Gastroduodenal Mucosal Injury Profile in Long-Term Low-Dose Aspirin Users and Its Influencing Factors

Background: Low-dose aspirin is the most common drug used for prevention of cardiovascular and cerebrovascular events. Long-term aspirin therapy can induce gastroduodenal mucosal injury, even in a very low dose (10 mg daily). The frequency of gastroduodenal injuries among long-term low-dose aspirin users in Indonesia is currently unknown. The aim of this study is to determine the prevalence of gastroduodenal mucosal injury, endoscopic findings, and influencing factors among long-term low-dose aspirin users in Cipto Mangunkusumo Hospital.Method: This study was a cross-sectional study conducted in Cipto Mangunkusumo Hospital, Jakarta. Subjects were patients aged ≥ 18 years old who had been using low-dose aspirin (75-325 mg) for at least the preceding 28 days. Ninety-five subjects were recruited consecutively in the period of December 2015 – April 2016. History taking, upper endoscopic examination, and histopathology examination for Helicobacter pylori infection were performed in all subjects. Endoscopic findings such as erosions and ulcers were assessed as mucosal injuries. Data were analysed to find prevalence, bivariate analysis (Chi-square test), and multivariate analysis (logistic regression test).Results: Mucosal injury was found in 49 subjects (51.6%; 95% CI: 41.6–61.7%), mucosal erosion in 38 subjects (40%; 95% CI: 30.2–49.9%) and ulcers in 11 subjects (11.6%; 95% CI: 5.2–18.0%). Only 44.9% patients with mucosal injury had dyspepsia symptoms. Double antiplatelet therapy increased the risk of mucosal injury (OR = 3.3; 95% CI: 1.3–8.5). However, proton pump inhibitor (PPI) decreased the risk of mucosal injury (OR = 0,2; 95% CI: 0,04 – 0,60).Conclusion: Gastroduodenal mucosal injury was found in more than half of long-term low-dose aspirin users. Double antiplatelet therapy increased the risk of mucosal injury, while PPI effectively reduced the risk.

Long-term aspirin use and intratumoral gene expression in prostate cancer.

106 Background: Pharmacoepidemiologic studies suggest prognostic benefits of aspirin in prostate cancer. We hypothesized that prostate cancer tissue from regular aspirin users at cancer diagnosis compared to nonusers is characterized by specific transcriptional changes. Methods: We analyzed tumor whole-transcriptome data from men diagnosed with prostate cancer during prospective follow up of the Physicians Health Study 1 (PHS1, n1 = 150), initially a randomized-controlled trial of aspirin for prevention of cardiovascular disease and cancer. We compared the expression of putative aspirin target genes ( PTGS2, CTNNB1, MYC, AXIN2, PTGER3) between regular aspirin users ( ≥ 3 x 324 mg/week) and non-users at cancer diagnosis. We used Gene Set Enrichment Analysis to identify Gene Ontology biological process gene sets (total, 3609) associated with aspirin use. Leading edge genes of ≥ 3 functionally related gene sets were summarized in a meta-gene score. Results were validated among prostate cancer patients from the Health-Professionals Follow-up Study (HPFS, n2 = 254; aspirin use, ≥ 2 x/week). Results: Regular aspirin use was common (65% in PHS1; 45% in HPFS) and not associated with age, stage, and Gleason grade. In PHS1, none of the predefined genes were associated with aspirin use (all p &gt; 0.05). 26 gene sets were downregulated in aspirin users at a false discovery rate (FDR) &lt; 0.25 (9 at FDR &lt; 0.05). 11 gene sets were clustered functionally around ribosome function and protein translation. A “ribosome” score of 96 genes was higher in aspirin users compared to nonusers (difference, 35.5 standard deviations [SD]; p = 0.0001). There was no dose-dependency for cumulative duration of aspirin use before cancer diagnosis ( ptrend = 0.17) or time since stopping use among non-users at diagnosis ( p = 0.32). In HPFS, neither the pre-defined target genes (all p &gt; 0.18) nor the score were associated with aspirin use (difference, –9.8 SD; p = 0.18). Conclusions: Although RNA acetylation and resulting intratumoral gene expression changes due to aspirin use may be biologically plausible, we were unable to corroborate this association in two-long term prospective studies. Short-term trials might assess if aspirin has direct effects on tumor gene expression.

Effects of aspirin on small-cell lung cancer mortality and metastatic presentation

Although meta-analysis data have shown that taking regular aspirin may reduce lung cancer mortality, individual trial data results are conflicting, and the data on the effects of aspirin on different histological subtypes of lung tumours, in particular small-cell lung cancer, are sparse.We conducted a prospective observational study of 313 patients with a new diagnosis of small-cell lung cancer and recorded use of aspirin before and after tumour diagnosis.Seventy-one (23%) patients were taking regular daily aspirin for more than 2 years at the time of tumour diagnosis. We found that regular use of aspirin had no effect on survival nor metastatic presentation compared to data from small-cell lung cancer patients not taking aspirin.The lack of survival benefit in patients with small-cell lung cancer taking long-term aspirin may be due to the low expression of cyclooxygenase-2 in small-cell lung cancer tissue.